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Aging and disease    2018, Vol. 9 Issue (4) : 664-673     DOI: 10.14336/AD.2017.0930
Orginal Article |
N-acetylcysteine Treatment Reduces Age-related Hearing Loss and Memory Impairment in the Senescence-Accelerated Prone 8 (SAMP8) Mouse Model
Marie Aurore1, Meunier Johann2, Brun Emilie3, Malmstrom Susanna1, Baudoux Veronique1, Flaszka Elodie1, Naert Gaëlle1, Roman François2, Cosnier-Pucheu Sylvie1, Gonzalez-Gonzalez Sergio1,*
1CILcare, Parc Scientifique Agropolis, Montpellier, France
2Amylgen, Montferrier-sur-Lez, France
3Correlative Microscopy and Electron Tomography Platform, Hopital Saint Eloi, Montpellier, France
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Abstract  

Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly population. SAMP8 mouse model presents accelerated senescence and has been identified as a model of gerontological research. SAMP8 displays a progressive age-related decline in brain function associated with a progressive hearing loss mimicking human aging memory deficits and ARHL. The molecular mechanisms associated with SAMP8 senescence process involve oxidative stress leading to chronic inflammation and apoptosis. Here, we studied the effect of N-acetylcysteine (NAC), an antioxidant, on SAMP8 hearing loss and memory to determine the potential interest of this model in the study of new antioxidant therapies. We observed a strong decrease of auditory brainstem response thresholds from 45 to 75 days of age and an increase of distortion product amplitudes from 60 to 75 days in NAC treated group compared to vehicle. Moreover, NAC treated group presented also an increase of memory performance at 60 and 105 days of age. These results confirm that NAC delays the senescence process by slowing the age-related hearing loss, protecting the cochlear hair cells and improving memory, suggesting that antioxidants could be a pharmacological target for age-related hearing and memory loss.

Keywords SAMP8      hearing loss      antioxidant      N-acetylcysteine      aging     
Corresponding Authors: Gonzalez-Gonzalez Sergio   
About author:

Equal contribution.

Issue Date: 01 August 2018
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Marie Aurore
Meunier Johann
Brun Emilie
Malmstrom Susanna
Baudoux Veronique
Flaszka Elodie
Naert Gaëlle
Roman François
Cosnier-Pucheu Sylvie
Gonzalez-Gonzalez Sergio
Cite this article:   
Marie Aurore,Meunier Johann,Brun Emilie, et al. N-acetylcysteine Treatment Reduces Age-related Hearing Loss and Memory Impairment in the Senescence-Accelerated Prone 8 (SAMP8) Mouse Model[J]. Aging and disease, 2018, 9(4): 664-673.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2017.0930     OR     http://www.aginganddisease.org/EN/Y2018/V9/I4/664
Figure 1.  Experimental procedure and animal weight

A) Schema of the experimental study. B) Mouse body weight evolution of NAC or vehicle treated group during the study. Data are shown as mean ± SEM. Significance was set at **p < 0.01. n = 6 mice by group.

Figure 2.  ABR thresholds representation

Auditory Brain Response thresholds of NAC (red line) and vehicle (black) treated mice at 8, 16, 20, 24 and 32KHz at the indicated age (A-F). The age of mice is indicated on each the graph (days old). ABR thresholds of NAC (red line) and vehicle (black) treated mice at 16 kHz (G) and 24 KHz (H) during the time experiment. Data are shown as median ± MAD. Significance was set at *p < 0.05 and ** p < 0.01. n = 6 mice by group.

Figure 3.  Distortion product otoacustic emission amplitude representation

DPOAE amplitude level of NAC (red line) and vehicle (black line) at 1, 4, 6, 8, 10, 12, 16, 20, 25 and 32 kHz and an intensity of 63 dB SPL. The age of mice is indicated on each the graph (days old). Data are shown as mean ± SEM. Significance was set at *p < 0.05. n = 6 mice by group.

Figure 4.  Scanning electron microscopy cochleae representative images of mice treated with NAC (right panels) and vehicle (left panels)

A) Global view of middle part of cochlea showing the presence of IHC and OHC of treated mice. Arrows and asterisks mark the loss of OHC and IHC respectively. Scale bar = 15 µm. B) Magnification of OHC stereocilia of NAC and vehicle treated mice. Scale bar = 3 µm. C) Magnification of IHC stereocilia of NAC and vehicle treated mice. Scale bar = 5 µm. n = 3 mice by group. These images are representative images of 3 independent animals.

Figure 5.  Object recognition test representation

Working memory test of NAC and vehicle treated mice at 60 and 105 days old represented as % of frequency of interactions with the new object (A) and % of time spent with the new object (B) respectively. Data are shown as mean ± SEM. Significance was set at **p < 0.01 and ***p < 0.001. n = 6 mice by group.

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