Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2019, Vol. 10 Issue (3) : 664-675     DOI: 10.14336/AD.2018.0720
Review |
Reactive Astrocytes in Neurodegenerative Diseases
Kunyu Li1, Jiatong Li1, Jialin Zheng2, Song Qin1,*
1Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
2Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
Download: PDF(730 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Astrocytes, the largest and most numerous glial cells in the central nervous system (CNS), play a variety of important roles in regulating homeostasis, increasing synaptic plasticity and providing neuroprotection, thus helping to maintain normal brain function. At the same time, astrocytes can participate in the inflammatory response and play a key role in the progression of neurodegenerative diseases. Reactive astrocytes are strongly induced by numerous pathological conditions in the CNS. Astrocyte reactivity is initially characterized by hypertrophy of soma and processes, triggered by different molecules. Recent studies have demonstrated that neuroinflammation and ischemia can elicit two different types of reactive astrocytes, termed A1s and A2s. However, in the case of astrocyte reactivity in different neurodegenerative diseases, the recently published research issues remain a high level of conflict and controversy. So far, we still know very little about whether and how the function or reactivity of astrocytes changes in the progression of different neurodegenerative diseases. In this review, we aimed to briefly discuss recent studies highlighting the complex contribution of astrocytes in the process of various neurodegenerative diseases, which may provide us with new prospects for the development of an excellent therapeutic target for neurodegenerative diseases.

Keywords reactive astrocytes      neuroinflammation      neurodegenerative diseases     
Corresponding Authors: Qin Song   
About author:

These authors contributed equally to this study.

Issue Date: 11 May 2018
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Kunyu Li
Jiatong Li
Jialin Zheng
Song Qin
Cite this article:   
Kunyu Li,Jiatong Li,Jialin Zheng, et al. Reactive Astrocytes in Neurodegenerative Diseases[J]. Aging and disease, 2019, 10(3): 664-675.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2018.0720     OR     http://www.aginganddisease.org/EN/Y2019/V10/I3/664
Figure 1.  Astrocytes play a critical role in supporting neurons in the CNS

Astrocytes support neuronal functions in multiple ways. Indeed, the extracellular levels of ions and neurotransmitters can affect the excitability of neurons. (1) High concentrations of extracellular potassium can trigger the glycolysis of astrocytes, which can enhance the release of lactate and pyruvate, thereby supporting neuronal metabolism. (2) Astrocytes can take up glutamate and convert it to glutamine, which is then released into the extracellular space and taken up by neurons to resynthesize glutamate. Any deregulation of these mechanisms is a common condition for neurodegenerative diseases. (3) Under the circumstances of brain injury, disease or inflammatory insult, toxic proinflammatory mediators are secreted and released by astrocytes, which will act on neurons and may affect the survival of neurons.

Reactive astrocytesMolecular expressionRefs
A1
astrocytes
Up
regulation
Inflammatory signaling through NF-κB[105, 106]
Glutamate and ATP release[107, 108]
Inflammatory mediators secretion (prostaglandinD2, IFN-γ, and TGF-β)[93, 109]
Lcn2 secretion[110]
IL-1α, C1q, TNF[9, 10]
Down
regulation
GPC4, GPC6, SPARCL1 expression[111, 112]
Excitatory amino acid transporter 2 (EAAT2), Glutamate transporter 1 (GLT1)[113, 114]
Trophic factor release[9, 115]
Lactate transportation[85]
GABA release through GAT-3[116]
A2
astrocytes
Up
regulation
Inflammatory signaling through STAT3[27, 29]
Thrombospondins (THBS1 and THBS2)[33]
Aquaporin-4[34]
HMGB1 and β-2 integrin[35]
Trophic factor release (BDNF, VEGF and bFGF)[9, 36, 37]
Down
regulation
H2-D1, Gbp2, Fkbp5, Srgn[10]
Table 1  The molecular expression changes between two different types of reactive astrocytes.
Figure 2.  Roles of reactive astrocytes in the process of neuroinflammation or brain injury

Neuroinflammation mainly induces the formation of A1 reactive astrocytes (A1s), which exhibit differential expression of astrocytic receptors, transporters, transmitters, as well as the changes of protein release and inflammatory factors. These changes may result in loss of neuroprotective function or neurological toxicity, a collapse of the brain-blood barrier and an increase in inflammation of the brain, which eventually results in deaths of neurons and causes neurodegenerative diseases. While A1s can upregulate many genes that are destructive to synapses, A2 reactive astrocytes (A2s) can upregulate many neurotrophic factors promoting the survival of neurons.

Figure 3.  Characteristics of reactive astrocytes in different neurodegenerative diseases

Various molecules can trigger the reactivity of astrocytes, which involves their morphological, transcriptional and functional changes. Different neurodegenerative diseases lead to a variety of changes in reactive astrocytes, which may ultimately cause them to release fewer neurotrophic factors and produce more inflammatory factors. This effect largely depends on different neurodegeneration-related factors, and the molecules they produce and secrete into the microenvironment surrounding the functional neurons in the brain. Aβ, amyloid β; SOD, superoxide dismutase-1; TDP-43, TAR DNA-binding protein 43; CN/NFAT, Calcineurin/Nuclear factor of activated T-cells; NOS, Nitric Oxide Synthase; JAK, Janus Kinase; ROS, reactive oxygen species; TGM6, Transglutaminase 6

[1] Benjamin Kacerovsky J, Murai KK (2016). Stargazing: Monitoring subcellular dynamics of brain astrocytes. Neuroscience, 323:84-95.
[2] Vasile F, Dossi E, Rouach N (2017). Human astrocytes: structure and functions in the healthy brain. Brain Struct Funct, 222:2017-2029.
[3] Gengatharan A, Bammann RR, Saghatelyan A (2016). The Role of Astrocytes in the Generation, Migration, and Integration of New Neurons in the Adult Olfactory Bulb. Front Neurosci, 10:149.
[4] Arango-Lievano M, Jeanneteau F (2016). Timing and crosstalk of glucocorticoid signaling with cytokines, neurotransmitters and growth factors. Pharmacol Res, 113:1-17.
[5] Allaman I, Belanger M, Magistretti PJ (2011). Astrocyte-neuron metabolic relationships: for better and for worse. Trends Neurosci, 34:76-87.
[6] Schousboe A, Scafidi S, Bak LK, Waagepetersen HS, McKenna MC (2014). Glutamate metabolism in the brain focusing on astrocytes. Adv Neurobiol, 11:13-30.
[7] Phillips EC, Croft CL, Kurbatskaya K, O’Neill MJ, Hutton ML, Hanger DP, et al. (2014). Astrocytes and neuroinflammation in Alzheimer’s disease. Biochem Soc Trans, 42:1321-1325.
[8] Rivetti di Val Cervo P, Romanov RA, Spigolon G, Masini D, Martin-Montanez E, Toledo EM, et al. (2017). Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson’s disease model. Nat Biotechnol, 35:444-452.
[9] Liddelow SA, Barres BA (2017). Reactive Astrocytes: Production, Function, and Therapeutic Potential. Immunity, 46:957-967.
[10] Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 541:481-487.
[11] Sofroniew MV, Vinters HV (2010). Astrocytes: biology and pathology. Acta Neuropathol, 119:7-35.
[12] Taft JR, Vertes RP, Perry GW (2005). Distribution of GFAP+ astrocytes in adult and neonatal rat brain. Int J Neurosci, 115:1333-1343.
[13] Hofmann K, Rodriguez-Rodriguez R, Gaebler A, Casals N, Scheller A, Kuerschner L (2017). Astrocytes and oligodendrocytes in grey and white matter regions of the brain metabolize fatty acids. Sci Rep, 7:10779.
[14] Duchesne PY, Gerebtzoff MA, Brotchi J (1981). Four types of reactive astrocytes. Bibl Anat:313-316.
[15] Volterra A, Meldolesi J (2005). Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci, 6:626-640.
[16] Sykova E, Chvatal A (1993). Extracellular ionic and volume changes: the role in glia-neuron interaction. J Chem Neuroanat, 6:247-260.
[17] Muller HW, Matthiessen HP, Schmalenbach C, Schroeder WO (1991). Glial support of CNS neuronal survival, neurite growth and regeneration. Restor Neurol Neurosci, 2:229-232.
[18] Yang D, Peng C, Li X, Fan X, Li L, Ming M, et al. (2008). Pitx3-transfected astrocytes secrete brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor and protect dopamine neurons in mesencephalon cultures. J Neurosci Res, 86:3393-3400.
[19] Cregg JM, DePaul MA, Filous AR, Lang BT, Tran A, Silver J (2014). Functional regeneration beyond the glial scar. Exp Neurol, 253:197-207.
[20] Theodosis DT, Piet R, Poulain DA, Oliet SH (2004). Neuronal, glial and synaptic remodeling in the adult hypothalamus: functional consequences and role of cell surface and extracellular matrix adhesion molecules. Neurochem Int, 45:491-501.
[21] Inyushin M, Kucheryavykh LY, Kucheryavykh YV, Nichols CG, Buono RJ, Ferraro TN, et al. (2010). Potassium channel activity and glutamate uptake are impaired in astrocytes of seizure-susceptible DBA/2 mice. Epilepsia, 51:1707-1713.
[22] Das T, Hoarau JJ, Jaffar Bandjee MC, Maquart M, Gasque P (2015). Multifaceted innate immune responses engaged by astrocytes, microglia and resident dendritic cells against Chikungunya neuroinfection. J Gen Virol, 96:294-310.
[23] Kajihara H, Tsutsumi E, Kinoshita A, Nakano J, Takagi K, Takeo S (2001). Activated astrocytes with glycogen accumulation in ischemic penumbra during the early stage of brain infarction: immunohistochemical and electron microscopic studies. Brain Res, 909:92-101.
[24] Giffard RG, Swanson RA (2005). Ischemia-induced programmed cell death in astrocytes. Glia, 50:299-306.
[25] Zhongwu Liu, Michael Chopp (2016). Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke. Prog Neurobiol. 144: 103-120
[26] Giordano G, Kavanagh TJ, Costa LG (2009). Mouse cerebellar astrocytes protect cerebellar granule neurons against toxicity of the polybrominated diphenylether (PBDE) mixture DE-71. Neurotoxicology, 30:326-329.
[27] Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, et al. (2006). Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med, 12:829-834.
[28] Hashioka S, Klegeris A, Qing H, McGeer PL (2011). STAT3 inhibitors attenuate interferon-gamma-induced neurotoxicity and inflammatory molecule production by human astrocytes. Neurobiol Dis, 41:299-307.
[29] Herrmann JE, Imura T, Song B, Qi J, Ao Y, Nguyen TK, et al. (2008). STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci, 28:7231-7243.
[30] Crosio C, Valle C, Casciati A, Iaccarino C, Carri MT (2011). Astroglial inhibition of NF-kappaB does not ameliorate disease onset and progression in a mouse model for amyotrophic lateral sclerosis (ALS). PLoS One, 6:e17187.
[31] Brambilla R, Persaud T, Hu X, Karmally S, Shestopalov VI, Dvoriantchikova G, et al. (2009). Transgenic inhibition of astroglial NF-kappa B improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation. J Immunol, 182:2628-2640.
[32] Dvoriantchikova G, Barakat D, Brambilla R, Agudelo C, Hernandez E, Bethea JR, et al. (2009). Inactivation of astroglial NF-kappa B promotes survival of retinal neurons following ischemic injury. Eur J Neurosci, 30:175-185.
[33] Christopherson KS, Ullian EM, Stokes CC, Mullowney CE, Hell JW, Agah A, et al. (2005). Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell, 120:421-433.
[34] Zador Z, Stiver S, Wang V, Manley GT (2009). Role of aquaporin-4 in cerebral edema and stroke. Handb Exp Pharmacol:159-170.
[35] Hayakawa K, Pham LD, Arai K, Lo EH (2014). Reactive astrocytes promote adhesive interactions between brain endothelium and endothelial progenitor cells via HMGB1 and beta-2 integrin signaling. Stem Cell Res, 12:531-538.
[36] Arregui L, Benitez JA, Razgado LF, Vergara P, Segovia J (2011). Adenoviral astrocyte-specific expression of BDNF in the striata of mice transgenic for Huntington’s disease delays the onset of the motor phenotype. Cell Mol Neurobiol, 31:1229-1243.
[37] Wang L, Lin F, Wang J, Wu J, Han R, Zhu L, et al. (2012). Truncated N-terminal huntingtin fragment with expanded-polyglutamine (htt552-100Q) suppresses brain-derived neurotrophic factor transcription in astrocytes. Acta Biochim Biophys Sin (Shanghai), 44:249-258.
[38] Phatnani H, Maniatis T (2015). Astrocytes in neurodegenerative disease. Cold Spring Harb Perspect Biol, 7.
[39] Hamby ME, Sofroniew MV (2010). Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics, 7:494-506.
[40] Rossi D, Volterra A (2009). Astrocytic dysfunction: insights on the role in neurodegeneration. Brain Res Bull, 80:224-232.
[41] Whalley K (2014). Neurodegenerative disease: propagating pathology. Nat Rev Neurosci, 15:565.
[42] Szutowicz A, Bielarczyk H, Ronowska A, Gul-Hinc S, Klimaszewska-Lata J, Dys A, et al. (2014). Intracellular redistribution of acetyl-CoA, the pivotal point in differential susceptibility of cholinergic neurons and glial cells to neurodegenerative signals. Biochem Soc Trans, 42:1101-1106.
[43] Szutowicz A, Bielarczyk H, Jankowska-Kulawy A, Pawelczyk T, Ronowska A (2013). Acetyl-CoA the key factor for survival or death of cholinergic neurons in course of neurodegenerative diseases. Neurochem Res, 38:1523-1542.
[44] Montie HL, Durcan TM (2013). The cell and molecular biology of neurodegenerative diseases: an overview. Front Neurol, 4:194.
[45] Vakalopoulos C (2017). Alzheimer’s Disease: The Alternative Serotonergic Hypothesis of Cognitive Decline. J Alzheimers Dis, 60:859-866.
[46] McGeer PL, McGeer EG (2002). Local neuroinflammation and the progression of Alzheimer’s disease. J Neurovirol, 8:529-538.
[47] Thinakaran G, Koo EH (2008). Amyloid precursor protein trafficking, processing, and function. J Biol Chem, 283:29615-29619.
[48] Bailey JA, Ray B, Greig NH, Lahiri DK (2011). Rivastigmine lowers Abeta and increases sAPPalpha levels, which parallel elevated synaptic markers and metabolic activity in degenerating primary rat neurons. PLoS One, 6:e21954.
[49] Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, et al. (2003). Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med, 9:453-457.
[50] Pihlaja R, Koistinaho J, Kauppinen R, Sandholm J, Tanila H, Koistinaho M (2011). Multiple cellular and molecular mechanisms are involved in human Abeta clearance by transplanted adult astrocytes. Glia, 59:1643-1657.
[51] Cole SL, Vassar R (2007). The Alzheimer’s disease beta-secretase enzyme, BACE1. Mol Neurodegener, 2:22.
[52] Acosta C, Anderson HD, Anderson CM (2017). Astrocyte dysfunction in Alzheimer disease. J Neurosci Res, 95(12):2430-2447
[53] Vincent AJ, Gasperini R, Foa L, Small DH (2010). Astrocytes in Alzheimer’s disease: emerging roles in calcium dysregulation and synaptic plasticity. J Alzheimers Dis, 22:699-714.
[54] Jo S, Yarishkin O, Hwang YJ, Chun YE, Park M, Woo DH, et al. (2014). GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease. Nat Med, 20:886-896.
[55] Kamphuis W, Kooijman L, Orre M, Stassen O, Pekny M, Hol EM (2015). GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild-type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer’s disease. Glia, 63:1036-1056.
[56] Nagele RG, Wegiel J, Venkataraman V, Imaki H, Wang KC, Wegiel J (2004). Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease. Neurobiol Aging, 25:663-674.
[57] Li C, Zhao R, Gao K, Wei Z, Yin MY, Lau LT, et al. (2011). Astrocytes: implications for neuroinflammatory pathogenesis of Alzheimer’s disease. Curr Alzheimer Res, 8:67-80.
[58] Kashon ML, Ross GW, O’Callaghan JP, Miller DB, Petrovitch H, Burchfiel CM, et al. (2004). Associations of cortical astrogliosis with cognitive performance and dementia status. J Alzheimers Dis, 6:595-604; discussion 73-81.
[59] Farina C, Aloisi F, Meinl E (2007). Astrocytes are active players in cerebral innate immunity. Trends Immunol, 28:138-145.
[60] Simpson JE, Ince PG, Lace G, Forster G, Shaw PJ, Matthews F, et al. (2010). Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain. Neurobiol Aging, 31:578-590.
[61] Salminen A, Ojala J, Suuronen T, Kaarniranta K, Kauppinen A (2008). Amyloid-beta oligomers set fire to inflammasomes and induce Alzheimer’s pathology. J Cell Mol Med, 12:2255-2262.
[62] Orre M, Kamphuis W, Osborn LM, Jansen AHP, Kooijman L, Bossers K, et al. (2014). Isolation of glia from Alzheimer’s mice reveals inflammation and dysfunction. Neurobiol Aging, 35:2746-2760.
[63] Allaman I, Gavillet M, Belanger M, Laroche T, Viertl D, Lashuel HA, et al. (2010). Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability. J Neurosci, 30:3326-3338.
[64] Brugg B, Dubreuil YL, Huber G, Wollman EE, Delhaye-Bouchaud N, Mariani J (1995). Inflammatory processes induce beta-amyloid precursor protein changes in mouse brain. Proc Natl Acad Sci U S A, 92:3032-3035.
[65] Zhao J, O’Connor T, Vassar R (2011). The contribution of activated astrocytes to Abeta production: implications for Alzheimer’s disease pathogenesis. J Neuroinflammation, 8:150.
[66] Guo Z, Cupples LA, Kurz A, Auerbach SH, Volicer L, Chui H, et al. (2000). Head injury and the risk of AD in the MIRAGE study. Neurology, 54:1316-1323.
[67] Siman R, Card JP, Nelson RB, Davis LG (1989). Expression of beta-amyloid precursor protein in reactive astrocytes following neuronal damage. Neuron, 3:275-285.
[68] Nadler Y, Alexandrovich A, Grigoriadis N, Hartmann T, Rao KS, Shohami E, et al. (2008). Increased expression of the gamma-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury. Glia, 56:552-567.
[69] Nutt JG, Wooten GF (2005). Clinical practice. Diagnosis and initial management of Parkinson’s disease. N Engl J Med, 353:1021-1027.
[70] Albin RL (2006). Parkinson’s disease: background, diagnosis, and initial management. Clin Geriatr Med, 22:735-751, v.
[71] Rappold PM, Tieu K (2010). Astrocytes and therapeutics for Parkinson’s disease. Neurotherapeutics, 7:413-423.
[72] Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, et al. (2010). Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One, 5:e8762.
[73] Wang HL, Chou AH, Wu AS, Chen SY, Weng YH, Kao YC, et al. (2011). PARK6 PINK1 mutants are defective in maintaining mitochondrial membrane potential and inhibiting ROS formation of substantia nigra dopaminergic neurons. Biochim Biophys Acta, 1812:674-684.
[74] Lieu CA, Chinta SJ, Rane A, Andersen JK (2013). Age-related behavioral phenotype of an astrocytic monoamine oxidase-B transgenic mouse model of Parkinson’s disease. PLoS One, 8:e54200.
[75] Kohler C, Eriksson LG, Flood PR, Hardie JA, Okuno E, Schwarcz R (1988). Quinolinic acid metabolism in the rat brain. Immunohistochemical identification of 3-hydroxyanthranilic acid oxygenase and quinolinic acid phosphoribosyltransferase in the hippocampal region. J Neurosci, 8:975-987.
[76] Hirsch EC, Hunot S (2009). Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol, 8:382-397.
[77] Halliday GM, Stevens CH (2011). Glia: initiators and progressors of pathology in Parkinson’s disease. Mov Disord, 26:6-17.
[78] Ciesielska A, Joniec I, Kurkowska-Jastrzebska I, Cudna A, Przybylkowski A, Czlonkowska A, et al. (2009). The impact of age and gender on the striatal astrocytes activation in murine model of Parkinson’s disease. Inflamm Res, 58:747-753.
[79] Lee HJ, Suk JE, Patrick C, Bae EJ, Cho JH, Rho S, et al. (2010). Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem, 285:9262-9272.
[80] Barcia C, Ros CM, Annese V, Gomez A, Ros-Bernal F, Aguado-Llera D, et al. (2012). IFN-gamma signaling, with the synergistic contribution of TNF-alpha, mediates cell specific microglial and astroglial activation in experimental models of Parkinson’s disease. Cell Death Dis, 3:e379.
[81] Gu XL, Long CX, Sun L, Xie C, Lin X, Cai H (2010). Astrocytic expression of Parkinson’s disease-related A53T alpha-synuclein causes neurodegeneration in mice. Mol Brain, 3:12.
[82] Sriram K, Benkovic SA, Hebert MA, Miller DB, O’Callaghan JP (2004). Induction of gp130-related cytokines and activation of JAK2/STAT3 pathway in astrocytes precedes up-regulation of glial fibrillary acidic protein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of neurodegeneration: key signaling pathway for astrogliosis in vivo? J Biol Chem, 279:19936-19947.
[83] L’Episcopo F, Serapide MF, Tirolo C, Testa N, Caniglia S, Morale MC, et al. (2011). A Wnt1 regulated Frizzled-1/beta-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection. Mol Neurodegener, 6:49.
[84] Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. (2011). Amyotrophic lateral sclerosis. Lancet, 377:942-955.
[85] Ferraiuolo L, Higginbottom A, Heath PR, Barber S, Greenald D, Kirby J, et al. (2011). Dysregulation of astrocyte-motoneuron cross-talk in mutant superoxide dismutase 1-related amyotrophic lateral sclerosis. Brain, 134:2627-2641.
[86] Van Damme P, Bogaert E, Dewil M, Hersmus N, Kiraly D, Scheveneels W, et al. (2007). Astrocytes regulate GluR2 expression in motor neurons and their vulnerability to excitotoxicity. Proc Natl Acad Sci U S A, 104:14825-14830.
[87] Martorana F, Brambilla L, Valori CF, Bergamaschi C, Roncoroni C, Aronica E, et al. (2012). The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals. Hum Mol Genet, 21:826-840.
[88] Papadeas ST, Kraig SE, O’Banion C, Lepore AC, Maragakis NJ (2011). Astrocytes carrying the superoxide dismutase 1 (SOD1G93A) mutation induce wild-type motor neuron degeneration in vivo. Proc Natl Acad Sci U S A, 108:17803-17808.
[89] Lepore AC, Rauck B, Dejea C, Pardo AC, Rao MS, Rothstein JD, et al. (2008). Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nat Neurosci, 11:1294-1301.
[90] Pardo AC, Wong V, Benson LM, Dykes M, Tanaka K, Rothstein JD, et al. (2006). Loss of the astrocyte glutamate transporter GLT1 modifies disease in SOD1(G93A) mice. Exp Neurol, 201:120-30.
[91] Chiu IM, Phatnani H, Kuligowski M, Tapia JC, Carrasco MA, Zhang M, et al. (2009). Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice. Proc Natl Acad Sci U S A, 106:20960-20965.
[92] Haidet-Phillips AM, Hester ME, Miranda CJ, Meyer K, Braun L, Frakes A, et al. (2011). Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol, 29:824-828.
[93] Phatnani HP, Guarnieri P, Friedman BA, Carrasco MA, Muratet M, O’Keeffe S, et al. (2013). Intricate interplay between astrocytes and motor neurons in ALS. Proc Natl Acad Sci U S A, 110:E756-765.
[94] Hashioka S, Klegeris A, Schwab C, McGeer PL (2009). Interferon-gamma-dependent cytotoxic activation of human astrocytes and astrocytoma cells. Neurobiol Aging, 30:1924-1935.
[95] Shibata N, Yamamoto T, Hiroi A, Omi Y, Kato Y, Kobayashi M (2010). Activation of STAT3 and inhibitory effects of pioglitazone on STAT3 activity in a mouse model of SOD1-mutated amyotrophic lateral sclerosis. Neuropathology, 30:353-360.
[96] McFarland HF, Martin R (2007). Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol, 8:913-919.
[97] Brosnan CF, Raine CS (2013). The astrocyte in multiple sclerosis revisited. Glia, 61:453-465.
[98] Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, et al. (2012). Genomic analysis of reactive astrogliosis. J Neurosci, 32:6391-6410.
[99] Stuve O, Youssef S, Slavin AJ, King CL, Patarroyo JC, Hirschberg DL, et al. (2002). The role of the MHC class II transactivator in class II expression and antigen presentation by astrocytes and in susceptibility to central nervous system autoimmune disease. J Immunol, 169:6720-6732.
[100] Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, et al. (2012). Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J Clin Invest, 122:2454-2468.
[101] Perriard G, Mathias A, Enz L, Canales M, Schluep M, Gentner M, et al. (2015). Interleukin-22 is increased in multiple sclerosis patients and targets astrocytes. J Neuroinflammation, 12:119.
[102] Yi H, Bai Y, Zhu X, Lin L, Zhao L, Wu X, et al. (2014). IL-17A induces MIP-1alpha expression in primary astrocytes via Src/MAPK/PI3K/NF-kB pathways: implications for multiple sclerosis. J Neuroimmune Pharmacol, 9:629-641.
[103] Blazevski J, Petkovic F, Momcilovic M, Jevtic B, Miljkovic D, Mostarica Stojkovic M (2013). High interleukin-10 expression within the central nervous system may be important for initiation of recovery of Dark Agouti rats from experimental autoimmune encephalomyelitis. Immunobiology, 218:1192-1199.
[104] Chen C, Zhong X, Smith DK, Tai W, Yang J, Zou Y, et al. (2017). Astrocyte-Specific Deletion of Sox2 Promotes Functional Recovery After Traumatic Brain Injury. Cereb Cortex:1-16.
[105] Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, et al. (2005). Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med, 202:145-156.
[106] Lian H, Yang L, Cole A, Sun L, Chiang AC, Fowler SW, et al. (2015). NFkappaB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer’s disease. Neuron, 85:101-115.
[107] Orellana JA, Froger N, Ezan P, Jiang JX, Bennett MV, Naus CC, et al. (2011). ATP and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels. J Neurochem, 118:826-840.
[108] Orellana JA, Shoji KF, Abudara V, Ezan P, Amigou E, Saez PJ, et al. (2011). Amyloid beta-induced death in neurons involves glial and neuronal hemichannels. J Neurosci, 31:4962-4977.
[109] Aebischer J, Cassina P, Otsmane B, Moumen A, Seilhean D, Meininger V, et al. (2011). IFNgamma triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1. Cell Death Differ, 18:754-768.
[110] Bi F, Huang C, Tong J, Qiu G, Huang B, Wu Q, et al. (2013). Reactive astrocytes secrete lcn2 to promote neuron death. Proc Natl Acad Sci U S A, 110:4069-4074.
[111] Allen NJ, Bennett ML, Foo LC, Wang GX, Chakraborty C, Smith SJ, et al. (2012). Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature, 486:410-414.
[112] Kucukdereli H, Allen NJ, Lee AT, Feng A, Ozlu MI, Conatser LM, et al. (2011). Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC. Proc Natl Acad Sci U S A, 108:E440-449.
[113] Howland DS, Liu J, She Y, Goad B, Maragakis NJ, Kim B, et al. (2002). Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci U S A, 99:1604-1609.
[114] Behrens PF, Franz P, Woodman B, Lindenberg KS, Landwehrmeyer GB (2002). Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation. Brain, 125:1908-1922.
[115] Chou SY, Weng JY, Lai HL, Liao F, Sun SH, Tu PH, et al. (2008). Expanded-polyglutamine huntingtin protein suppresses the secretion and production of a chemokine (CCL5/RANTES) by astrocytes. J Neurosci, 28:3277-3290.
[116] Wojtowicz AM, Dvorzhak A, Semtner M, Grantyn R (2013). Reduced tonic inhibition in striatal output neurons from Huntington mice due to loss of astrocytic GABA release through GAT-3. Front Neural Circuits, 7:188.
[1] Han Rongrong, Liu Zeyue, Sun Nannan, Liu Shu, Li Lanlan, Shen Yan, Xiu Jianbo, Xu Qi. BDNF Alleviates Neuroinflammation in the Hippocampus of Type 1 Diabetic Mice via Blocking the Aberrant HMGB1/RAGE/NF-κB Pathway[J]. Aging and disease, 2019, 10(3): 611-625.
[2] Sarkar Saumyendra N., Russell Ashley E., Engler-Chiurazzi Elizabeth B., Porter Keyana N., Simpkins James W.. MicroRNAs and the Genetic Nexus of Brain Aging, Neuroinflammation, Neurodegeneration, and Brain Trauma[J]. Aging and disease, 2019, 10(2): 329-352.
[3] Wei Zhuang,Lifeng Yue,Xiaofang Dang,Fei Chen,Yuewen Gong,Xiaolan Lin,Yumin Luo. Rosenroot (Rhodiola): Potential Applications in Aging-related Diseases[J]. Aging and disease, 2019, 10(1): 134-146.
[4] Antonina Luca, Carmela Calandra, Maria Luca. Molecular Bases of Alzheimer’s Disease and Neurodegeneration: The Role of Neuroglia[J]. Aging and disease, 2018, 9(6): 1134-1152.
[5] Yong-Fei Zhao, Qiong Zhang, Jian-Feng Zhang, Zhi-Yin Lou, Hen-Bing Zu, Zi-Gao Wang, Wei-Cheng Zeng, Kai Yao, Bao-Guo Xiao. The Synergy of Aging and LPS Exposure in a Mouse Model of Parkinson’s Disease[J]. Aging and disease, 2018, 9(5): 785-797.
[6] Chen Yali, Yin Mengmei, Cao Xuejin, Hu Gang, Xiao Ming. Pro- and Anti-inflammatory Effects of High Cholesterol Diet on Aged Brain[J]. Aging and disease, 2018, 9(3): 374-390.
[7] Shen Ting, You Yuyi, Joseph Chitra, Mirzaei Mehdi, Klistorner Alexander, Graham Stuart L., Gupta Vivek. BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders[J]. Aging and disease, 2018, 9(3): 523-536.
[8] Szybińska Aleksandra, Leśniakx Leśniak. P53 Dysfunction in Neurodegenerative Diseases - The Cause or Effect of Pathological Changes?[J]. Aging and disease, 2017, 8(4): 506-518.
[9] Su Ruijun, Sun Min, Wang Wei, Zhang Jianliang, Zhang Li, Zhen Junli, Qian Yanjing, Zheng Yan, Wang Xiaomin. A Novel Immunosuppressor, (5R)-5-Hydroxytriptolide, Alleviates Movement Disorder and Neuroinflammation in a 6-OHDA Hemiparkinsonian Rat Model[J]. Aging and disease, 2017, 8(1): 31-43.
[10] Rolova Taisia, Dhungana Hiramani, Korhonen Paula, Valonen Piia, Kolosowska Natalia, Konttinen Henna, Kanninen Katja, Tanila Heikki, Malm Tarja, Koistinaho Jari. Deletion of Nuclear Factor kappa B p50 Subunit Decreases Inflammatory Response and Mildly Protects Neurons from Transient Forebrain Ischemia-induced Damage[J]. Aging and disease, 2016, 7(4): 450-465.
[11] Redmann Matthew, Darley-Usmar Victor, Zhang Jianhua. The Role of Autophagy, Mitophagy and Lysosomal Functions in Modulating Bioenergetics and Survival in the Context of Redox and Proteotoxic Damage: Implications for Neurodegenerative Diseases[J]. Aging and disease, 2016, 7(2): 150-162.
[12] Onyango Isaac G., Dennis Jameel, Khan Shaharyah M.. Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies[J]. Aging and disease, 2016, 7(2): 201-214.
[13] Amandine E. Bonnet, Yannick Marchalant. Potential Therapeutical Contributions of the Endocannabinoid System towards Aging and Alzheimer’s Disease[J]. Aging and disease, 2015, 6(5): 400-405.
[14] Juliana B. Hoppe, Christianne G. Salbego, Helena Cimarosti. SUMOylation: Novel Neuroprotective Approach for Alzheimer’s Disease?[J]. Aging and disease, 2015, 6(5): 322-330.
[15] João M. N. Duarte,Patrícia F. Schuck,Gary L. Wenk,Gustavo C. Ferreira. Metabolic Disturbances in Diseases with Neurological Involvement[J]. Aging and Disease, 2014, 5(4): 238-255.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd