Abstract
Purpose :
To determine whether the 5xFAD mouse, a model of Alzheimer’s disease (AD), shows changes in the expression of glutamate (Glu) and gamma-aminobutyric acid (GABA) neurotransmitters and in the physiology of the retinal ganglion cells (RGCs) during the temporal course of AD.
Methods :
Retinas from youngs (2-3 months, n=20) and adults (6-7 months, n=20) 5xFAD and WT mice were employed. For each animal, one eye was collected and fixed for immunogold-silver staining to detect Glu and GABA in the retina. RGCs activity was recorded using a multielectrode array under scotopic and photopic conditions from the contralateral eye. All methods used here are in compliance with bioethical certification.
Results :
Glu was predominantly visualized in the RGC layer in youngs and adults 5xFAD mice, but not in the young or adults WT. GABA was predominantly found in the inner retina in young and adults WT and the RGC layer of youngs 5xFAD but not in the adults 5xFAD. In scotopic conditions, the firing rate of RGCs was higher in youngs 5xFAD compared to youngs WT (all numeric results are presented as 25% percentile, median, 75% percentile in Hz. 5xFAD = 0.559, 3.025, 8.44. WT = 0.31, 1.819, 7.02. Significative difference (SD), Mann Whitney test (MW test), p<0.05), while adults 5xFAD shows lower firing rate compared to the adults WT (5xFAD= 0.223, 1.081, 3.82. WT= 0.415, 2.04, 5.85. SD, MW test, p<0.05). In photopic conditions was a high firing rate for the youngs 5xFAD compared to youngs WT (5xFAD= 0.5, 2.918, 9.96. WT= 0.30, 1.858, 6.83. SD, MW test, p<0.05). However, no difference was found between the adults 5xFAD and the adults WT.
Conclusions :
We reported changes in the levels of Glu and GABA in the RGC layer for 5xFAD mice retinas and a concomitant upregulation of the RGCs physiology for spontaneous scotopic and photopic activity in the youngs 5xFAD. In the scotopic conditions the spontaneous RGCs firing activity of the adults 5xFAD is downregulated, but not in photopic conditions. Our results support the idea that the integrated homeostatic network, which enables functional stability of central circuits, it’s disrupted too in the retina in the AD depending on illumination condition.
This is a 2020 ARVO Annual Meeting abstract.