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Aging and disease    2015, Vol. 6 Issue (5) : 349-368     DOI: 10.14336/AD.2015.0330
Review Article |
Dopamine Receptors and Neurodegeneration
Claudia Rangel-Barajas1,2,*(), Israel Coronel3, Benjamín Florán4
1Department of Psychological and Brain Sciences Program in Neurosciences, Indiana University Bloomington, Bloomington, IN 47405, USA
2Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
3Health Sciences Faculty, Anahuac University, Mexico Norte, State of Mexico, Mexico.
4Department of Physiology, Biophysics and Neurosciences CINVESTAV-IPN, Mexico.
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Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson’s disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases.

Keywords Dopamine receptors      neurotoxicity      neurodegeneration      Parkinson’s disease     
Corresponding Authors: Claudia Rangel-Barajas     E-mail:
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present address: Kunming Biomed International, Kunming, Yunnan, 650500, China

Issue Date: 01 October 2015
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Claudia Rangel-Barajas
Israel Coronel
Benjamín Florán
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Claudia Rangel-Barajas,Israel Coronel,Benjamín Florán. Dopamine Receptors and Neurodegeneration[J]. Aging and disease, 2015, 6(5): 349-368.
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Figure 1.  The D1-like DA Receptors Intracellular Signal Pathways. Shows the DA mediated effects through D1-like DA receptors that by the activation of intracellular signals. Stimulatory effects are indicated with red arrows and inhibitory effects in blue line ended with a circle. cAMP, 3'-5'-cyclic adenosine monophosphate; αs/olf or αq ATP, active Gα protein; PKA, protein kinase A; DARPP-32, dopamine and cyclic AMP-regulated phosphoprotein, 32 kDa; AC, adenylyl cyclase; PP1, PP2A or PP2B, protein-phosphatase 1, 2A or 2B; PKC, protein kinase C; PLC, phospholipase C; IP3, inositol triphosphate; mTOR, mammalian target of rapamycin; PIP2, phosphatidylinositol 2; Ca2+, calcium; MAPK, mitogen-activated protein kinase EPAC-GEF, guanine-nucleotide-exchange factor of Rap1; Rap1, Ras proximate 1. AMPA, α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; NMDA, N-methyl-D-aspartate; GABAA, γ-Aminobutyric acid A; CREB; cAMP response element-binding protein.
Figure 2.  The D2-like DA Receptors Intracellular Signal Pathways. Shows the DA mediated effects through D2-like DA receptors that occur by a complex activation of intracellular signals that are related with events such as neurodevelopment, proteasomal degradation, cell proliferation and cognitive process. Stimulatory effects are indicated with red arrows, dashed red arrow indicates plausible activation and inhibitory effects in blue line ended with a circle. cAMP, 3'-5'-cyclic adenosine monophosphate; αi/o ATP, active Gαi/o protein; PKA, protein kinase A; DARPP-32, dopamine and cyclic AMP-regulated phosphoprotein, 32 kDa; AC, adenylyl cyclase; PP1, PP2A or PP2B, protein-phosphatase 1, 2A or 2B; MAPK, mitogen-activated protein kinase; PKC, protein kinase C; Akt, thymoma viral proto-oncogene; GSK-3, Glycogen Synthase Kinase-3; PLCβ, phospholipase C isoform β; PI3K, phosphatidylinositol 3-kinase; PIP2, PIP3, phosphatidylinositol 2 and 3; IP3, inositol triphosphate; Ca2+, calcium ; GIRK, G protein coupled inward rectifier potassium; MEK; Raf,; ERK, extracellular signal-regulated kinase protein kinase; PDK, phosphoinositide-dependant kinase; mTOR, mammalian target of rapamycin; p70S6, p70S6 kinase; rpS6, ribosomal S6 protein; 4E-BP, eukaryotic initiation factor 4E-binding protein 1.
Figure 3.  Oxidative stress and Neurotoxicity. A. Shows the neurotoxic mechanisms of DA and neurotoxins used to mimic PD in the dopaminergic neuron. DA and the neurotoxins 6-hydroxydopmine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), cause reactive species of oxygen (ROS) affecting the mitochondrial function and lipoperoxidation and cytoskeletal disorganization, which leads energy crisis and neuronal death. MPTP is first incorporated into the glial cells and metabolized to MPP+, this metabolite can cross the membrane through the DA transporter (DAT) to reach intracellular compartments in DAergic neuron, while 6-OHDA can directly cross through DAT. B. Neurotoxicity by renin-angiotensin system (RAS) activation and DA receptors. In RAS, angiotensinogen is converted to Angiotensin I (AI) by renin, AI is converted into Angiotensin II (AII) thought angiotensin converting enzyme (ACE), AII mediate their actions by angiotensin receptors AT1 and AT2Rs. AT1Rs activate the nicotidamine adenine dinucleotide phosphate oxidase complex (NADPH), which is the major source of ROS causing mitochondrial dysfunction and inflammatory response. The interaction AT1Rs with of D1 and D3Rs increases the DA response while D5Rs can regulate the AT1Rs by proteasome mechanisms. DA receptors are also related with immune response in T cells.
[1] Ben-Jonathan N (1985). Dopamine: a prolactin-inhibiting hormone. Endocr Rev, 6:564-589.
[2] Jackson DM, Westlind-Danielsson A (1994). Dopamine receptors: molecular biology, biochemistry and behavioural aspects. Pharmacol Ther, 64:291-370.
[3] Forn J, Krueger BK, Greengard P (1974). Adenosine 3',5'-monophosphate content in rat caudate nucleus: demonstration of dopaminergic and adrenergic receptors. Science, 186:1118-1120.
[4] Arisawa M, Makino T, Izumi S, Iizuka R (1983). Effect of prostaglandin D2 on gonadotropin release from rat anterior pituitary in vitro. Fertil Steril, 39:93-96.
[5] Greengard P, Allen PB, Nairn AC (1999). Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron, 23:435-447.
[6] Civelli O, Bunzow JR, Grandy DK (1993). Molecular diversity of the dopamine receptors. Annu Rev Pharmacol Toxicol, 33:281-307.
[7] Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998). Dopamine receptors: from structure to function. Physiol Rev, 78:189-225.
[8] Wamsley JK, Gehlert DR, Filloux FM, Dawson TM (1989). Comparison of the distribution of D-1 and D-2 dopamine receptors in the rat brain. J Chem Neuroanat, 2:119-137.
[9] Savasta M, Dubois A, Scatton B (1986). Autoradiographic localization of D1 dopamine receptors in the rat brain with [3H]SCH 23390. Brain Res, 375:291-301.
[10] Boyson SJ, McGonigle P, Molinoff PB (1986). Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain. J Neurosci, 6:3177-3188.
[11] Cadet JL, Jayanthi S, McCoy MT, Beauvais G, Cai NS (2010). Dopamine D1 receptors, regulation of gene expression in the brain, and neurodegeneration. CNS Neurol Disord Drug Targets, 9:526-538.
[12] Graybiel AM, Aosaki T, Flaherty AW, Kimura M (1994). The basal ganglia and adaptive motor control. Science, 265:1826-1831.
[13] Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR (1997). Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. Science, 278:1907-1916.
[14] Sunahara RK, Taussig R (2002). Isoforms of mammalian adenylyl cyclase: multiplicities of signaling. Mol Interv, 2:168-184.
[15] Kim C, Vigil D, Anand G, Taylor SS (2006). Structure and dynamics of PKA signaling proteins. Eur J Cell Biol, 85:651-654.
[16] Akimoto M, Selvaratnam R, McNicholl ET, Verma G, Taylor SS, Melacini G (2013). Signaling through dynamic linkers as revealed by PKA. Proc Natl Acad Sci USA, 110:14231-14236.
[17] Rajput PS, Kharmate G, Somvanshi RK, Kumar U (2009). Colocalization of dopamine receptor subtypes with dopamine and cAMP-regulated phosphoprotein (DARPP-32) in rat brain. Neurosci Res, 65:53-63.
[18] Nishi A, Snyder GL, Fienberg AA, Fisone G, Aperia A, Nairn AC, Greengard P (1999). Requirement for DARPP-32 in mediating effect of dopamine D2 receptor activation. Eur J Neurosci, 11:2589-2592.
[19] Bibb JA, Snyder GL, Nishi A, Yan Z, Meijer L, Fienberg AA, Tsai LH, Kwon YT, Girault JA, Czernik AJ, Huganir RL, Hemmings HC, Jr Nairn AC, Greengard P (1999). Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons. Nature, 402:669-671.
[20] Undieh AS (2010). Pharmacology of signaling induced by dopamine D(1)-like receptor activation. Pharmacol Ther, 128:37-60.
[21] Surmeier DJ, Bargas J, Hemmings HC Jr, Nairn AC, Greengard P (1995). Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons. Neuron, 14:385-397.
[22] Schiffmann SN, Desdouits F, Menu R, Greengard P, Vincent JD, Vanderhaeghen JJ, Girault JA (1998). Modulation of the voltage-gated sodium current in rat striatal neurons by DARPP-32, an inhibitor of protein phosphatase. Eur J Neurosci, 10:1312-1320.
[23] Roche KW, O'Brien RJ, Mammen AL, Bernhardt J, Huganir RL (1996). Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron, 16:1179-1188.
[24] Hernandez-Lopez S, Tkatch T, Perez-Garci E, Galarraga E, Bargas J, Hamm H, Surmeier DJ (2000). D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLC[beta]1-IP3-calcineurin-signaling cascade. J Neurosci, 20:8987-8995.
[25] Santini E, Valjent E, Usiello A, Carta M, Borgkvist A, Girault JA, Herve D, Greengard P, Fisone G (2007). Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in L-DOPA-induced dyskinesia. J Neurosci, 27:6995-7005.
[26] Altschuler DL, Peterson SN, Ostrowski MC, Lapetina EG (1995). Cyclic AMP-dependent activation of Rap1b. J Biol Chem, 270:10373-10376.
[27] Kawasaki H, Springett GM, Mochizuki N, Toki S, Nakaya M, Matsuda M, Housman DE, Graybiel AM (1998). A family of cAMP-binding proteins that directly activate Rap1. Science, 282:2275-2279.
[28] Bos JL, de Rooij J, Reedquist KA (2001). Rap1 signalling: adhering to new models. Nat Rev Mol Cell Biol, 2:369-377.
[29] Neves SR, Ram PT, Iyengar R (2002). G protein pathways. Science, 296:1636-1639.
[30] Lezcano N, Mrzljak L, Eubanks S, Levenson R, Goldman-Rakic P, Bergson C (2000). Dual signaling regulated by calcyon, a D1 dopamine receptor interacting protein. Science, 287:1660-1664.
[31] Ha CM, Park D, Han JK, Jang JI, Park JY, Hwang EM, Seok H, Chang S (2012). Calcyon forms a novel ternary complex with dopamine D1 receptor through PSD-95 protein and plays a role in dopamine receptor internalization. J Biol Chem, 287:31813-31822.
[32] Loos M, Pattij T, Janssen MC, Counotte DS, Schoffelmeer AN, Smit AB, Spijker S, van Gaalen MM (2010). Dopamine receptor D1/D5 gene expression in the medial prefrontal cortex predicts impulsive choice in rats. Cereb Cortex, 20:1064-1070.
[33] Koh PO, Bergson C, Undie AS, Goldman-Rakic PS, Lidow MS (2003). Up-regulation of the D1 dopamine receptor-interacting protein, calcyon, in patients with schizophrenia. Arch Gen Psychiatry, 60:311-319.
[34] Nishi A, Fisone G, Snyder GL, Dulubova I, Aperia A, Nairn AC, Greengard P (1999). Regulation of Na+, K+-ATPase isoforms in rat neostriatum by dopamine and protein kinase C. J Neurochem, 73:1492-1501.
[35] Gomes P, Soares-da-Silva P (2002). Na(+)/H(+) exchanger activity and dopamine D(1)-like receptor function in two opossum kidney cell clonal sublines. Cell Physiol Biochem, 12:259-268.
[36] Arnaldo FB, Villar VA, Konkalmatt PR, Owens SA, Asico LD, Jones JE, Yang J, Lovett DL, Armando I, Jose PA, Concepcion GP (2014). D1-like dopamine receptors downregulate Na+-K+-ATPase activity and increase cAMP production in the posterior gills of the blue crab Callinectes sapidus. Am J Physiol Regul Integr Comp Physiol, 307:R634-42.
[37] Kebabian JW, Greengard P (1971). Dopamine-sensitive adenyl cyclase: possible role in synaptic transmission. Science, 174:1346-1349.
[38] Nishi A, Snyder GL, Nairn AC, Greengard P (1999). Role of calcineurin and protein phosphatase-2A in the regulation of DARPP-32 dephosphorylation in neostriatal neurons. J Neurochem, 72:2015-2021.
[39] Chio CL, Lajiness ME, Huff RM (1994). Activation of heterologously expressed D3 dopamine receptors: comparison with D2 dopamine receptors. Mol Pharmacol, 45:51-60.
[40] MacKenzie RG, VanLeeuwen D, Pugsley TA, Shih YH, Demattos S, Tang L, Todd RD, O'Malley KL (1994). Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur J Pharmacol, 266:79-85.
[41] Zaworski PG, Alberts GL, Pregenzer JF, Im WB, Slightom JL, Gill GS (1999). Efficient functional coupling of the human D3 dopamine receptor to G(o) subtype of G proteins in SH-SY5Y cells. Br J Pharmacol, 128:1181-1188.
[42] Robinson SW, Caron MG (1997). Selective inhibition of adenylyl cyclase type V by the dopamine D3 receptor. Mol Pharmacol, 52:508-514.
[43] Cooper DM, Mons N, Karpen JW (1995). Adenylyl cyclases and the interaction between calcium and cAMP signalling. Nature, 374:421-424.
[44] Cooper DM (2003). Regulation and organization of adenylyl cyclases and cAMP. Biochem J, 375:517-529.
[45] Watts VJ (2002). Molecular mechanisms for heterologous sensitization of adenylate cyclase. J Pharmacol Exp Ther, 302:1-7.
[46] Krishnan V, Graham A, Mazei-Robison MS, Lagace DC, Kim KS, Birnbaum S, Eisch AJ, Han PL, Storm DR, Zachariou V, Nestler EJ (2008). Calcium-sensitive adenylyl cyclases in depression and anxiety: behavioral and biochemical consequences of isoform targeting. Biol Psychiatry, 64:336-343.
[47] Rangel-Barajas C, Silva I, Lopez-Santiago LM, Aceves J, Erlij D, Floran B (2011). L-DOPA-induced dyskinesia in hemiparkinsonian rats is associated with up-regulation of adenylyl cyclase type V/VI and increased GABA release in the substantia nigra reticulata. Neurobiol Dis, 41:51-61.
[48] Mark MD, Herlitze S (2000). G-protein mediated gating of inward-rectifier K+ channels. Eur J Biochem, 267:5830-5836.
[49] Pillai G, Brown NA, McAllister G, Milligan G, Seabrook GR (1998). Human D2 and D4 dopamine receptors couple through betagamma G-protein subunits to inwardly rectifying K+ channels (GIRK1) in a Xenopus oocyte expression system: selective antagonism by L-741,626 and L-745,870 respectively. Neuropharmacology, 37:983-987.
[50] Davila V, Yan Z, Craciun LC, Logothetis D, Sulzer D (2003). D3 dopamine autoreceptors do not activate G-protein-gated inwardly rectifying potassium channel currents in substantia nigra dopamine neurons. J Neurosci, 23:5693-5697.
[51] Beom S, Cheong D, Torres G, Caron MG, Kim KM (2004). Comparative studies of molecular mechanisms of dopamine D2 and D3 receptors for the activation of extracellular signal-regulated kinase. J Biol Chem, 279:28304-28314.
[52] Luedtke RR, Mishra Y, Wang Q, Griffin SA, Bell-Horner C, Taylor M, Vangveravong S, Dillon GH, Huang RQ, Reichert DE, Mach RH (2012). Comparison o the binding and functional properties of two structurally different D2 dopamine receptor subtype selective compounds. ACS Chem Neurosci, 3:1050-1062.
[53] Lefkowitz RJ, Shenoy SK (2005). Transduction of receptor signals by beta-arrestins. Science, 308:512-517.
[54] Jin M, Min C, Zheng M, Cho DI, Cheong SJ, Kurose H, Kim KM (2013). Multiple signaling routes involved in the regulation of adenylyl cyclase and extracellular regulated kinase by dopamine D(2) and D(3) receptors. Pharmacol Res, 67:31-41.
[55] Gonzalez S, Rangel-Barajas C, Peper M, Lorenzo R, Moreno E, Ciruela F, Borycz J, Ortiz J, Lluis C, Franco R, McCormick PJ, Volkow ND, Rubinstein M, Floran B, Ferre S (2012). Dopamine D4 receptor, but not the ADHD-associated D4.7 variant, forms functional heteromers with the dopamine D2S receptor in the brain. Mol Psychiatry, 17:650-662.
[56] Brami-Cherrier K, Valjent E, Garcia M, Pages C, Hipskind RA, Caboche J (2002). Dopamine induces a PI3-kinase-independent activation of Akt in striatal neurons: a new route to cAMP response element-binding protein phosphorylation. J Neurosci, 22:8911-8921.
[57] Mannoury la Cour C, Salles MJ, Pasteau V, Millan MJ (2011). Signaling pathways leading to phosphorylation of Akt and GSK-3beta by activation of cloned human and rat cerebral D(2)and D(3) receptors. Mol Pharmacol, 79:91-105.
[58] Beaulieu JM, Tirotta E, Sotnikova TD, Masri B, Salahpour A, Gainetdinov RR, Borrelli E, Caron MG (2007). Regulation of Akt signaling by D2 and D3 dopamine receptors in vivo. J Neurosci, 27:881-885.
[59] Collo G, Zanetti S, Missale C, Spano P (2008). Dopamine D3 receptor-preferring agonists increase dendrite arborization of mesencephalic dopaminergic neurons via extracellular signal-regulated kinase phosphorylation. Eur J Neurosci, 28:1231-1240.
[60] Collo G, Bono F, Cavalleri L, Plebani L, Merlo Pich E, Millan MJ, Spano PF, Missale C (2012). Pre-synaptic dopamine D(3) receptor mediates cocaine-induced structural plasticity in mesencephalic dopaminergic neurons via ERK and Akt pathways. J Neurochem, 120:765-778.
[61] Hoeffer CA, Klann E (2010). mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci, 33:67-75.
[62] Peineau S, Bradley C, Taghibiglou C, Doherty A, Bortolotto ZA, Wang YT, Collingridge GL (2008). The role of GSK-3 in synaptic plasticity. Br J Pharmacol 153 Suppl 1:S428-37.
[63] Doble BW, Woodgett JR (2003). GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci, 116:1175-1186.
[64] Emamian ES (2012). AKT/GSK3 signaling pathway and schizophrenia. Front Mol Neurosci, 15:5-33.
[65] Salles MJ, Herve D, Rivet JM, Longueville S, Millan MJ, Girault JA, Mannoury la CourC (2013). Transient and rapid activation of Akt/GSK-3beta and mTORC1 signaling by D3 dopamine receptor stimulation in dorsal striatum and nucleus accumbens. J Neurochem, 125:532-544.
[66] Rosenberg PA (1988). Catecholamine toxicity in cerebral cortex in dissociated cell culture. J Neurosci, 8:2887-2894.
[67] Tanaka M, Sotomatsu A, Kanai H, Hirai S (1991). Dopa and dopamine cause cultured neuronal death in the presence of iron. J Neurol Sci, 101:198-203.
[68] Hoyt KR, Reynolds IJ, Hastings TG (1997). Mechanisms of dopamine-induced cell death in cultured rat forebrain neurons: interactions with and differences from glutamate-induced cell death. Exp Neurol, 143:269-281.
[69] Ben-Shachar D, Zuk R, Gazawi H, Ljubuncic P (2004). Dopamine toxicity involves mitochondrial complex I inhibition: implications to dopamine-related neuropsychiatric disorders. Biochem Pharmacol, 67:1965-1974.
[70] Cheng N, Maeda T, Kume T, Kaneko S, Kochiyama H, Akaike A, Goshima Y, Misu Y (1996). Differential neurotoxicity induced by L-DOPA and dopamine in cultured striatal neurons. Brain Res, 743:278-283.
[71] Luo Y, Umegaki H, Wang X, Abe R, Roth GS (1998). Dopamine induces apoptosis through an oxidation-involved SAPK/JNK activation pathway. J Biol Chem, 273:3756-3764.
[72] Di Filippo M, Picconi B, Costa C, Bagetta V, Tantucci M, Parnetti L, Calabresi P (2006). Pathways of neurodegeneration and experimental models of basal ganglia disorders: downstream effects of mitochondrial inhibition. Eur J Pharmacol, 545:65-72.
[73] Cadet J, D'Ham C, Douki T, Pouget JP, Ravanat JL, Sauvaigo S (1998). Facts and artifacts in the measurement of oxidative base damage to DNA. Free Radic Res, 29:541-550.
[74] Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, Verna JM (2001). Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog Neurobiol, 65:135-172.
[75] Wersinger C, Chen J, Sidhu A (2004). Bimodal induction of dopamine-mediated striatal neurotoxicity is mediated through both activation of D1 dopamine receptors and autoxidation. Mol Cell Neurosci, 25:124-137.
[76] Labandeira-Garcia JL, Rodriguez-Pallares J, Dominguez-Meijide A, Valenzuela R, Villar-Cheda B, Rodriguez-Perez AI (2013). Dopamine-angiotensin interactions in the basal ganglia and their relevance for Parkinson's disease. Mov Disord, 28:1337-1342.
[77] Li D, Scott L, Crambert S, Zelenin S, Eklof AC, Di Ciano L, Ibarra F, Aperia A (2012). Binding of losartan to angiotensin AT1 receptors increases dopamine D1 receptor activation. J Am Soc Nephrol, 23:421-428.
[78] Merchant KM, Letter AA, Gibb JW, Hanson GR (1988). Changes in the limbic neurotensin systems induced by dopaminergic drugs. Eur J Pharmacol, 153:1-9.
[79] Labandeira-Garcia JL, Rodriguez-Pallares J, Villar-Cheda B, Rodriguez-Perez AI, Garrido-Gil P, Guerra MJ (2011). Aging, Angiotensin system and dopaminergic degeneration in the substantia nigra. Aging Dis, 2:257-274.
[80] Labandeira-Garcia JL, Garrido-Gil P, Rodriguez-Pallares J, Valenzuela R, Borrajo A, Rodriguez-Perez AI (2014). Brain renin-angiotensin system and dopaminergic cell vulnerability. Front Neuroanat 8:8-67.
[81] Chabrashvili T, Kitiyakara C, Blau J, Karber A, Aslam S, Welch WJ, Wilcox CS (2003). Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression. Am J Physiol Regul Integr Comp Physiol, 285:R117-24.
[82] Jones ES, Vinh A, McCarthy CA, Gaspari TA, Widdop RE (2008). AT2 receptors: functional relevance in cardiovascular disease. Pharmacol Ther, 120:292-316.
[83] Vazquez E, Coronel I, Bautista R, Romo E, Villalon CM, Avila-Casado MC, Soto V, Escalante B (2005). Angiotensin II-dependent induction of AT(2) receptor expression after renal ablation. Am J Physiol Renal Physiol, 288:F207-13.
[84] Kehoe PG, Wilcock GK (2007). Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease?. Lancet Neurol, 6:373-378.
[85] Stegbauer J, Lee DH, Seubert S, Ellrichmann G, Manzel A, Kvakan H, Muller DN, Gaupp S, Rump LC, Gold R, Linker RA (2009). Role of the renin-angiotensin system in autoimmune inflammation of the central nervous system. Proc Natl Acad Sci USA, 106:14942-14947.
[86] Labandeira-Garcia JL, Rodriguez-Pallares J, Rodriguez-Perez AI, Garrido-Gil P, Villar-Cheda B, Valenzuela R, Guerra MJ (2012). Brain angiotensin and dopaminergic degeneration: relevance to Parkinson's disease. Am J Neurodegener Dis, 1:226-244.
[87] Kerr DS, Bevilaqua LR, Bonini JS, Rossato JI, Kohler CA, Medina JH, Izquierdo I, Cammarota M (2005). Angiotensin II blocks memory consolidation through an AT2 receptor-dependent mechanism. Psychopharmacology (Berl), 179:529-535.
[88] Hermann K, McDonald W, Unger T, Lang RE, Ganten D (1984). Angiotensin biosynthesis and concentrations in brain of normotensive and hypertensive rats. J Physiol (Paris), 79:471-480.
[89] Stornetta RL, Hawelu-Johnson CL, Guyenet PG, Lynch KR (1988). Astrocytes synthesize angiotensinogen in brain. Science, 242:1444-1446.
[90] Kumar A, Rassoli A, Raizada MK (1988). Angiotensinogen gene expression in neuronal and glial cells in primary cultures of rat brain. J Neurosci Res, 19:287-290.
[91] Noh KM, Koh JY (2000). Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes. J Neurosci, 20:RC111.
[92] Gao HM, Liu B, Zhang W, Hong JS (2003). Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson's disease. FASEB J, 17:1954-1956.
[93] Wu DC, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003). NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci USA, 100:6145-6150.
[94] Rodriguez-Pallares J, Parga JA, Munoz A, Rey P, Guerra MJ, Labandeira-Garcia JL (2007). Mechanism of 6-hydroxydopamine neurotoxicity: the role of NADPH oxidase and microglial activation in 6-hydroxydopamine-induced degeneration of dopaminergic neurons. J Neurochem, 103:145-156.
[95] Rodriguez-Pallares J, Rey P, Parga JA, Munoz A, Guerra MJ, Labandeira-Garcia JL (2008). Brain angiotensin enhances dopaminergic cell death via microglial activation and NADPH-derived ROS. Neurobiol Dis, 31:58-73.
[96] Joglar B, Rodriguez-Pallares J, Rodriguez-Perez AI, Rey P, Guerra MJ, Labandeira-Garcia JL (2009). The inflammatory response in the MPTP model of Parkinson's disease is mediated by brain angiotensin: relevance to progression of the disease. J Neurochem, 109:656-669.
[97] Babior BM (2004). NADPH oxidase. Curr Opin Immunol, 16:42-47.
[98] Rey P, Lopez-Real A, Sanchez-Iglesias S, Munoz A, Soto-Otero R, Labandeira-Garcia JL (2007). Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for dopaminergic neurons. Neurobiol Aging, 28:555-567.
[99] Villar-Cheda B, Dominguez-Meijide A, Valenzuela R, Granado N, Moratalla R, Labandeira-Garcia JL (2014). Aging-related dysregulation of dopamine and angiotensin receptor interaction. Neurobiol Aging, 35:1726-1738.
[100] Quinlan JT, Phillips MI (1981). Immunoreactivity for an angiotensin II-like peptide in the human brain. Brain Res, 205:212-218.
[101] Simonnet G, Giorguieff-Chesselet MF, Carayon A, Bioulac B, Cesselin F, Glowinski J, Vincent JD (1981). Angiotensin II and nigostriatal system (author's transl). J Physiol (Paris), 77:71-79.
[102] Brownfield MS, Reid IA, Ganten D, Ganong WF (1982). Differential distribution of immunoreactive angiotensin and angiotensin-converting enzyme in rat brain. Neuroscience, 7:1759-1769.
[103] Chai SY, Mendelsohn FA, Paxinos G (1987). Angiotensin converting enzyme in rat brain visualized by quantitative in vitro autoradiography. Neuroscience, 20:615-627.
[104] Rodriguez-Pallares J, Quiroz CR, Parga JA, Guerra MJ, Labandeira-Garcia JL (2004). Angiotensin II increases differentiation of dopaminergic neurons from mesencephalic precursors via angiotensin type 2 receptors. Eur J Neurosci, 20:1489-1498.
[105] Garrido-Gil P, Valenzuela R, Villar-Cheda B, Lanciego JL, Labandeira-Garcia JL (2013). Expression of angiotensinogen and receptors for angiotensin and prorenin in the monkey and human substantia nigra: an intracellular renin-angiotensin system in the nigra. Brain Struct Funct, 218:373-388.
[106] Mendelsohn FA, Jenkins TA, Berkovic SF (1993). Effects of angiotensin II on dopamine and serotonin turnover in the striatum of conscious rats. Brain Res, 613:221-229.
[107] Gildea JJ (2009). Dopamine and angiotensin as renal counterregulatory systems controlling sodium balance. Curr Opin Nephrol Hypertens, 18:28-32.
[108] Li H, Armando I, Yu P, Escano C, Mueller SC, Asico L, Pascua A, Lu Q, Wang X, Villar VA, Jones JE, Wang Z, Periasamy A, Lau YS, Soares-da-Silva P, Creswell K, Guillemette G, Sibley DR, Eisner G, Gildea JJ, Felder RA, Jose PA (2008). Dopamine 5 receptor mediates ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells. J Clin Invest, 118:2180-2189.
[109] Zeng C, Asico LD, Wang X, Hopfer U, Eisner GM, Felder RA, Jose PA (2003). Angiotensin II regulation of AT1 and D3 dopamine receptors in renal proximal tubule cells of SHR. Hypertension, 41:724-729.
[110] Grammatopoulos TN, Jones SM, Ahmadi FA, Hoover BR, Snell LD, Skoch J, Jhaveri V V, Poczobutt AM, Weyhenmeyer JA, Zawada WM (2007). Angiotensin type 1 receptor antagonist losartan, reduces MPTP-induced degeneration of dopaminergic neurons in substantia nigra. Mol Neurodegener, 2:1-17.
[111] Zawada WM, Banninger GP, Thornton J, Marriott B, Cantu D, Rachubinski AL, Das M, Griffin WS, Jones SM (2011). Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade. J Neuroinflammation, 129:1-13
[112] Sonsalla PK, Coleman C, Wong LY, Harris SL, Richardson JR, Gadad BS, Li W, German DC (2013). The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism. Exp Neurol, 250:376-383.
[113] Lopez-Real A, Rey P, Soto-Otero R, Mendez-Alvarez E, Labandeira-Garcia JL (2005). Angiotensin-converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6-hydroxydopamine rat model of Parkinsonism. J Neurosci Res 81:865-873.
[114] Muñoz A, Rey P, Guerra MJ, Mendez-Alvarez E, Soto-Otero R, Labandeira-Garcia JL (2006). Reduction of dopaminergic degeneration and oxidative stress by inhibition of angiotensin converting enzyme in a MPTP model of parkinsonism. Neuropharmacology, 51:112-120.
[115] Sanchez-Iglesias S, Rey P, Mendez-Alvarez E, Labandeira-Garcia JL, Soto-Otero R (2007). Time-course of brain oxidative damage caused by intrastriatal administration of 6-hydroxydopamine in a rat model of Parkinson's disease. Neurochem Res, 32:99-105.
[116] Dominguez-Meijide A, Villar-Cheda B, Garrido-Gil P, Sierrra-Paredes G, Guerra MJ, Labandeira-Garcia JL (2014). Effect of chronic treatment with angiotensin type 1 receptor antagonists on striatal dopamine levels in normal rats and in a rat model of Parkinson's disease treated with L-DOPA. Neuropharmacology, 76:156-168.
[117] Brown DC, Steward LJ, Ge J, Barnes NM (1996). Ability of angiotensin II to modulate striatal dopamine release via the AT1 receptor in vitro and in vivo. Br J Pharmacol, 118:414-420.
[118] Muñoz A, Garrido-Gil P, Dominguez-Meijide A, Labandeira-Garcia JL (2014). Angiotensin type 1 receptor blockage reduces l-dopa-induced dyskinesia in the 6-OHDA model of Parkinson's disease. Involvement of vascular endothelial growth factor and interleukin-1beta. Exp Neurol 261C:720-732.
[119] Hussain T, Abdul-Wahab R, Kotak DK, Lokhandwala MF (1998). Bromocriptine regulates angiotensin II response on sodium pump in proximal tubules. Hypertension, 32:1054-1059.
[120] Zeng C, Luo Y, Asico LD, Hopfer U, Eisner GM, Felder RA, Jose PA (2003). Perturbation of D1 dopamine and AT1 receptor interaction in spontaneously hypertensive rats. Hypertension, 42:787-792.
[121] Valenzuela R, Barroso-Chinea P, Villar-Cheda B, Joglar B, Munoz A, Lanciego JL, Labandeira-Garcia JL (2010). Location of prorenin receptors in primate substantia nigra: effects on dopaminergic cell death. J Neuropathol Exp Neurol, 69:1130-1142.
[122] Jenkins TA, Wong JY, Howells DW, Mendelsohn FA, Chai SY (1999). Effect of chronic angiotensin-converting enzyme inhibition on striatal dopamine content in the MPTP-treated mouse. J Neurochem, 73:214-219.
[123] Reardon KA, Mendelsohn FA, Chai SY, Horne MK (2000). The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson's disease. Aust N Z J Med, 30:48-53.
[124] Ohshima K, Mogi M, Horiuchi M (2013). Therapeutic approach for neuronal disease by regulating renin-angiotensin system. Curr Hypertens Rev, 9:99-107.
[125] Platten M, Youssef S, Hur EM, Ho PP, Han MH, Lanz TV, Phillips LK, Goldstein MJ, Bhat R, Raine CS, Sobel RA, Steinman L (2009). Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Proc Natl Acad Sci USA, 106:14948-14953.
[126] Lanz TV, Ding Z, Ho PP, Luo J, Agrawal AN, Srinagesh H, Axtell R, Zhang H, Platten M, Wyss-Coray T, Steinman L (2010). Angiotensin II sustains brain inflammation in mice via TGF-beta. J Clin Invest, 120:2782-2794.
[127] Touyz RM (2004). Reactive oxygen species and angiotensin II signaling in vascular cells -- implications in cardiovascular disease. Braz J Med Biol Res, 37:1263-1273.
[128] Hoogwerf BJ (2010). Renin-angiotensin system blockade and cardiovascular and renal protection. Am J Cardiol, 105:30A-5A.
[129] Pacheco R, Prado CE, Barrientos MJ, Bernales S (2009). Role of dopamine in the physiology of T-cells and dendritic cells. J Neuroimmunol, 216:8-19.
[130] Bergquist J, Silberring J (1998). Identification of catecholamines in the immune system by electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom, 12:683-688.
[131] Cosentino M, Zaffaroni M, Ferrari M, Marino F, Bombelli R, Rasini E, Frigo G, Ghezzi A, Comi G, Lecchini S (2005). Interferon-gamma and interferon-beta affect endogenous catecholamines in human peripheral blood mononuclear cells: implications for multiple sclerosis. J Neuroimmunol, 162:112-121.
[132] McKenna F, McLaughlin PJ, Lewis BJ, Sibbring GC, Cummerson JA, Bowen-Jones D, Moots RJ (2002). Dopamine receptor expression on human T- and B-lymphocytes, monocytes, neutrophils, eosinophils and NK cells: a flow cytometric study. J Neuroimmunol, 132:34-40.
[133] Nakano K, Higashi T, Hashimoto K, Takagi R, Tanaka Y, Matsushita S (2008). Antagonizing dopamine D1-like receptor inhibits Th17 cell differentiation: preventive and therapeutic effects on experimental autoimmune encephalomyelitis. Biochem Biophys Res Commun, 373:286-291.
[134] Prado C, Contreras F, Gonzalez H, Diaz P, Elgueta D, Barrientos M, Herrada AA, Lladser A, Bernales S, Pacheco R (2012). Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity. J Immunol 188:3062-3070.
[135] Besser MJ, Ganor Y, Levite M (2005). Dopamine by itself activates either D2, D3 or D1/D5 dopaminergic receptors in normal human T-cells and triggers the selective secretion of either IL-10, TNFalpha or both. J Neuroimmunol, 169:161-171.
[136] Ilani T, Strous RD, Fuchs S (2004). Dopaminergic regulation of immune cells via D3 dopamine receptor: a pathway mediated by activated T cells. FASEB J, 18:1600-1602.
[137] Laman JD, Weller RO, (2013). Drainage of cells and soluble antigen from the CNS to regional lymph nodes. J Neuroimmune Pharmacol, 8:840-856.
[138] Radjavi A, Smirnov I, Kipnis J (2014). Brain antigen-reactive CD4+ T cells are sufficient to support learning behavior in mice with limited T cell repertoire. Brain Behav Immun, 35:58-63.
[139] Gonzalez H, Contreras F. Prado C, Elgueta D, Franz D, Bernales S, Pacheco R (2013). Dopamine receptor D3 expressed on CD4+ T cells favors neurodegeneration of dopaminergic neurons during Parkinson's disease. J Immunol, 190:5048-5056.
[140] Penney JB Jr, Young AB (1983). Speculations on the functional anatomy of basal ganglia disorders. Annu Rev Neurosci, 6:73-94.
[141] Albin RL, Young AB, Penney JB (1989). The functional anatomy of basal ganglia disorders. Trends Neurosci, 12:366-375.
[142] Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ,Jr, Sibley DR (1990). D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science, 250:1429-1432.
[143] Floran B, Aceves J, Sierra A, Martinez-Fong D (1990). Activation of D1 dopamine receptors stimulates the release of GABA in the basal ganglia of the rat. Neurosci Lett, 116:136-140.
[144] Floran B, Floran L, Sierra A, Aceves J (1997). D2 receptor-mediated inhibition of GABA release by endogenous dopamine in the rat globus pallidus. Neurosci Lett, 237:1-4.
[145] Cooper AJ, Stanford IM (2001). Dopamine D2 receptor mediated presynaptic inhibition of striatopallidal GABA(A) IPSCs in vitro. Neuropharmacology, 41:62-71.
[146] Obeso JA, Rodriguez-Oroz MC, Rodriguez M, Macias R, Alvarez L, Guridi J, Vitek J, DeLong MR (2000). Pathophysiologic basis of surgery for Parkinson's disease. Neurology, 55:S7-12.
[147] Napolitano M, Centonze D, Calce A, Picconi B, Spiezia S, Gulino A, Bernardi G, Calabresi P (2002). Experimental parkinsonism modulates multiple genes involved in the transduction of dopaminergic signals in the striatum. Neurobiol Dis, 10:387-395.
[148] Aubert I, Guigoni C, Hakansson K, Li Q, Dovero S, Barthe N, Bioulac BH, Gross CE, Fisone G, Bloch B, Bezard E (2005). Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia. Ann Neurol, 57:17-26.
[149] Silva I. Cortes H, Escartin E, Rangel C, Floran L, Erlij D, Aceves J, Floran B (2006). L-DOPA inhibits depolarization-induced [3H]GABA release in the dopamine-denervated globus pallidus of the rat: the effect is dopamine independent and mediated by D2-like receptors. J Neural Transm, 113:1847-1853.
[150] Prieto GA, Perez-Burgos A, Fiordelisio T, Salgado H, Galarraga E, Drucker-Colin R, Bargas J (2009). Dopamine D(2)-class receptor supersensitivity as reflected in Ca2+ current modulation in neostriatal neurons. Neuroscience, 164:345-350.
[151] Rangel-Barajas C, Silva I, Garcia-Ramirez M, Sanchez-Lemus E, Floran L, Aceves J, Erlij D, Floran B (2008). 6-OHDA-induced hemiparkinsonism and chronic L-DOPA treatment increase dopamine D1-stimulated [(3)H]-GABA release and [(3)H]-cAMP production in substantia nigra pars reticulata of the rat. Neuropharmacology, 55:704-711.
[152] Cai G, Wang HY, Friedman E (2002). Increased dopamine receptor signaling and dopamine receptor-G protein coupling in denervated striatum. J Pharmacol Exp Ther, 302:1105-1112.
[153] Alexander GE, Crutcher MD (1990). Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci, 13:266-271.
[154] Feyder M, Bonito-Oliva A, Fisone G (2011). L-DOPA-Induced Dyskinesia and Abnormal Signaling in Striatal Medium Spiny Neurons: Focus on Dopamine D1 Receptor-Mediated Transmission. Front Behav Neurosci, 5:1-10.
[155] Santini E, Feyder M, Gangarossa G, Bateup HS, Greengard P, Fisone G (2012). Dopamine- and cAMP-regulated phosphoprotein of 32-kDa (DARPP-32)-dependent activation of extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin complex 1 (mTORC1) signaling in experimental parkinsonism. J Biol Chem, 287:27806-27812.
[156] Park HY, Kang YM, Kang Y, Park TS, Ryu YK, Hwang JH, Kim YH, Chung BH, Nam KH, Kim MR, Lee CH, Han PL, Kim KS (2014). Inhibition of Adenylyl Cyclase Type 5 Prevents l-DOPA-Induced Dyskinesia in an Animal Model of Parkinson's Disease. J Neurosci, 34:11744-11753.
[157] Lee T, Seeman P, Rajput A, Farley IJ, Hornykiewicz O (1978). Receptor basis for dopaminergic supersensitivity in Parkinson's disease. Nature, 273:59-61.
[158] Levey AI, Hersch SM, Rye DB, Sunahara RK, Niznik HB, Kitt CA, Price DL, Maggio R, Brann MR, Ciliax BJ (1993). Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies. Proc Natl Acad Sci USA, 90:8861-8865.
[159] Levant B (1998). Differential distribution of D3 dopamine receptors in the brains of several mammalian species. Brain Res, 800:269-274.
[160] Prieto GA, Perez-Burgos A, Palomero-Rivero M, Galarraga E, Drucker-Colin R, Bargas J (2011). Upregulation of D2-class signaling in dopamine-denervated striatum is in part mediated by D3 receptors acting on Ca V 2.1 channels via PIP2 depletion. J Neurophysiol, 105:2260-2274.
[161] Cruz-Trujillo R, Avalos-Fuentes A, Rangel-Barajas C, Paz-Bermudez F, Sierra A, Escartin-Perez E, Aceves J, Erlij D, Floran B (2013). D3 dopamine receptors interact with dopamine D1 but not D4 receptors in the GABAergic terminals of the SNr of the rat. Neuropharmacology, 67:370-378.
[162] Avalos-Fuentes A, Loya-Lopez S, Flores-Perez A, Recillas-Morales S, Cortes H, Paz-Bermudez F, Aceves J, Erlij D, Floran B (2013). Presynaptic CaMKIIalpha modulates dopamine D3 receptor activation in striatonigral terminals of the rat brain in a Ca(2)(+) dependent manner. Neuropharmacology, 71:273-281.
[163] Bordet R, Ridray S, Carboni S, Diaz J, Sokoloff P, Schwartz JC (1997). Induction of dopamine D3 receptor expression as a mechanism of behavioral sensitization to levodopa. Proc Natl Acad Sci USA, 94:3363-3367.
[164] Sun J, Cairns NJ, Perlmutter JS, Mach RH, Xu J (2013). Regulation of dopamine D receptor in the striatal regions and substantia nigra in diffuse Lewy body disease. Neuroscience, 248C:112-126.
[165] Albarrán S, Ávalos-Fuentes A, Paz-Bermúdez F, Erlij D, Aceves J, Floran B (2013). Dopamine D3 receptor prevents D1 receptor stimulation of [3H] GABA release in substantia nigra pars reticulata of hemiparkinsonian dyskinetic rats. Soc Neursc Abstr, 240.06/M7.
[166] Van Kampen JM, Robertson HA (2005). A possible role for dopamine D3 receptor stimulation in the induction of neurogenesis in the adult rat substantia nigra. Neuroscience, 136:381-386.
[167] Van Kampen JM, Eckman CB (2006). Dopamine D3 receptor agonist delivery to a model of Parkinson's disease restores the nigrostriatal pathway and improves locomotor behavior. J Neurosci, 26:7272-7280.
[168] Fiorentini C, Busi C, Spano P, Missale C (2008). Role of receptor heterodimers in the development of L-dopa-induced dyskinesias in the 6-hydroxydopamine rat model of Parkinson's disease. Parkinsonism Relat Disord 14 Suppl, 2:S159-64.
[169] Marcellino D, Ferre S, Casado V, Cortes A, Le Foll B, Mazzola C, Drago F, Saur O, Stark H, Soriano A, Barnes C, Goldberg SR, Lluis C, Fuxe K, Franco R (2008). Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum. J Biol Chem, 283:26016-26025.
[170] Gutekunst CA, Li SH, Yi H, Mulroy JS, Kuemmerle S, Jones R, Rye D, Ferrante RJ, Hersch SM, Li XJ (1999). Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J Neurosci, 19:2522-2534.
[171] Quarrell O, O'Donovan KL, Bandmann O, Strong M (2012). The Prevalence of Juvenile Huntington's Disease: A Review of the Literature and Meta-Analysis. PLoS Curr Hunt Dis, 20:1-11
[172] Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr (1985). Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol, 44:559-577.
[173] Deng YP, Albin RL, Penney JB, Young AB, Anderson KD, Reiner A (2004). Differential loss of striatal projection systems in Huntington's disease: a quantitative immunohistochemical study. J Chem Neuroanat, 27:143-164.
[174] Cowan CM, Fan MM, Fan J, Shehadeh J, Zhang LY, Graham RK, Hayden MR, Raymond LA (2008). Polyglutamine-modulated striatal calpain activity in YAC transgenic huntington disease mouse model: impact on NMDA receptor function and toxicity. J Neurosci, 28:12725-12735.
[175] Duncan GE, Inada K, Koller BH anMoy SS (2010). Increased sensitivity to kainic acid in a genetic model of reduced NMDA receptor function. Brain Res, 1307:166-176.
[176] Estrada-Sanchez AM, Montiel T, Segovia J, Massieu L (2009). Glutamate toxicity in the striatum of the R6/2 Huntington's disease transgenic mice is age-dependent and correlates with decreased levels of glutamate transporters. Neurobiol Dis, 34:78-86.
[177] Brito VI, Rozanski VE, Beyer C, Kuppers E (2009). Dopamine regulates the expression of the glutamate transporter GLT1 but not GLAST in developing striatal astrocytes. J Mol Neurosci, 39:372-379.
[178] Rotaru DC, Lewis DA, Gonzalez-Burgos G (2007). Dopamine D1 receptor activation regulates sodium channel-dependent EPSP amplification in rat prefrontal cortex pyramidal neurons. J Physiol, 581:981-1000.
[179] Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973). Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci, 20:415-455.
[180] Bedard C, Wallman MJ, Pourcher E, Gould PV, Parent A, Parent M (2011). Serotonin and dopamine striatal innervation in Parkinson's disease and Huntington's chorea. Parkinsonism Relat Disord, 17:593-598.
[181] Ginovart N, Lundin A, Farde L, Halldin C, Backman L, Swahn CG, Pauli S and Sedvall G (1997). PET study of the pre- and post-synaptic dopaminergic markers for the neurodegenerative process in Huntington's disease. Brain, 120(Pt 3):503-514.
[182] Bohnen NI, Koeppe RA, Meyer P, Ficaro E, Wernette K. Kilbourn MR, Kuhl DE, Frey KA, Albin RL (2000). Decreased striatal monoaminergic terminals in Huntington disease. Neurology, 54:1753-1759.
[183] Garrett MC, Soares-da-Silva P (1992). Increased cerebrospinal fluid dopamine and 3,4-dihydroxyphenylacetic acid levels in Huntington's disease: evidence for an overactive dopaminergic brain transmission. J Neurochem, 58:101-106.
[184] Suzuki T, Miura M, Nishimura K, Aosaki T (2001). Dopamine-dependent synaptic plasticity in the striatal cholinergic interneurons. J Neurosci, 21:6492-6501.
[185] Richfield EK, O'Brien CF, Eskin T, Shoulson I (1991). Heterogeneous dopamine receptor changes in early and late Huntington's disease. Neurosci Lett, 132:121-126.
[186] Ariano MA, Aronin N, Difiglia M, Tagle DA, Sibley DR, Leavitt BR, Hayden MR, Levine MS (2002). Striatal neurochemical changes in transgenic models of Huntington's disease. J Neurosci Res, 68:716-729.
[187] Van Oostrom JC, Dekker M, Willemsen AT, de Jong BM, Roos RA, Leenders KL (2009). Changes in striatal dopamine D2 receptor binding in pre-clinical Huntington's disease. Eur J Neurol, 16:226-231.
[188] Backman L, Farde L (2001). Dopamine and cognitive functioning: brain imaging findings in Huntington's disease and normal aging. Scand J Psychol, 42:287-296.
[189] Carter RJ, Lione LA, Humby T, Mangiarini L, Mahal A, Bates GP, Dunnett SB, Morton AJ (1999). Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J Neurosci, 19:3248-3257.
[190] Lione LA, Carter RJ, Hunt M J, Bates GP, Morton AJ, Dunnett SB (1999). Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation. J Neurosci, 19:10428-10437.
[191] Gerfen CR, Miyachi S, Paletzki R, Brown P (2002). D1 dopamine receptor supersensitivity in the dopamine-depleted striatum results from a switch in the regulation of ERK1/2/MAP kinase. J Neurosci, 22:5042-5054.
[192] Augood SJ, Faull RL, Emson PC (1997). Dopamine D1 and D2 receptor gene expression in the striatum in Huntington's disease. Ann Neurol 42:215-221.
[193] Cha JH, Kosinski CM, Kerner JA, Alsdorf SA, Mangiarini L, Davies SW, Penney JB, Bates GP, Young AB (1998). Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci USA, 95:6480-6485.
[194] Bibb JA, Yan Z, Svenningsson P, Snyder GL, Pieribone VA, Horiuchi A, Nairn AC, Messer A, Greengard P (2000). Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice. Proc Natl Acad Sci USA, 97:6809-6814.
[195] Murphy-Nakhnikian A. Dorner JL, Fischer BI, Bower-Bir ND, Rebec GV (2012). Abnormal burst patterns of single neurons recorded in the substantia nigra reticulata of behaving 140 CAG Huntington's disease mice. Neurosci Lett, 512:1-5.
[196] Sarkar S, Krishna G, Imarisio S, Saiki S, O'Kane CJ, Rubinsztein DC (2008). A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin. Hum Mol Genet, 17:170-178.
[197] Lim NK, Hung LW, Pang TY, Mclean CA, Liddell JR, Hilton JB, Li QX, White AR, Hannan AJ, Crouch PJ (2014). Localized changes to glycogen synthase kinase-3 and collapsin response mediator protein-2 in the Huntington's disease affected brain. Hum Mol Gene, 23:4051-4063.
[198] Valencia A, Reeves PB, Sapp E, Li X, Alexander J, Kegel KB, Chase K. Aronin N, DiFiglia M (2010). Mutant huntingtin and glycogen synthase kinase 3-beta accumulate in neuronal lipid rafts of a presymptomatic knock-in mouse model of Huntington's disease. J Neurosci Res, 88:179-190.
[199] Beaulieu JM, Gainetdinov RR, Caron MG (2007). The Akt-GSK-3 signaling cascade in the actions of dopamine. Trends Pharmacol Sci, 28:166-172.
[200] Sutton LP, Rushlow WJ (2011). The effects of neuropsychiatric drugs on glycogen synthase kinase-3 signaling. Neuroscience, 199:116-124.
[201] Alimohamad H, Rajakumar N, Seah YH, Rushlow W (2005). Antipsychotics alter the protein expression levels of beta-catenin and GSK-3 in the rat medial prefrontal cortex and striatum. Biol Psychiatry, 57:533-542.
[202] Brusa L, Orlacchio A, Moschella V, Iani C, Bernardi G, Mercuri NB (2009). Treatment of the symptoms of Huntington's disease: preliminary results comparing aripiprazole and tetrabenazine. Mov Disord, 24:126-129.
[203] Tang TS, Chen X, Liu J, Bezprozvanny I (2007). Dopaminergic signaling and striatal neurodegeneration in Huntington's disease. J Neurosci, 27:7899-7910.
[204] Kasper LH, Shoemaker J (2010). Multiple sclerosis immunology: The healthy immune system vs the MS immune system. Neurology, 74:S2-8.
[205] Hemmer B, Nessler S, Zhou D, Kieseier B, Hartung HP (2006). Immunopathogenesis and immunotherapy of multiple sclerosis. Nat Clin Pract Neurol, 2:201-211.
[206] Cosentino M, Marino F (2013). Adrenergic and dopaminergic modulation of immunity in multiple sclerosis: teaching old drugs new tricks? J Neuroimmune Pharmacol, 8:163-179.
[207] Balkowiec-Iskra E, Kurkowska-Jastrzebska I, Joniec I, Ciesielska A, Czlonkowska A, Czlonkowski A (2007). Dopamine, serotonin and noradrenaline changes in the striatum of C57BL mice following myelin oligodendrocyte glycoprotein (MOG) 35-55 and complete Freund adjuvant (CFA) administration. Acta Neurobiol Exp (Wars), 67:379-388.
[208] Giorelli M, Livrea P, Trojano M (2005). Dopamine fails to regulate activation of peripheral blood lymphocytes from multiple sclerosis patients: effects of IFN-beta. J Interferon Cytokine Res, 25:395-406.
[209] Zaffaroni M, Marino F, Bombelli R, Rasini E, Monti M, Ferrari M, Ghezzi A, Comi G, Lecchini S, Cosentino M (2008). Therapy with interferon-beta modulates endogenous catecholamines in lymphocytes of patients with multiple sclerosis. Exp Neurol, 214:315-321.
[210] Seeman P, Van Tol HH (1994). Dopamine receptor pharmacology. Trends Pharmacol Sci, 15:264-270.
[211] Bissay V, De Klippel N, Herroelen L, Schmedding E, Buisseret T, Ebinger G, De Keyser J (1994). Bromocriptine therapy in multiple sclerosis: an open label pilot study. Clin Neuropharmacol, 17:473-476.
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