Background
Alzheimer's disease (AD) is a progressive neurodegenerative disease that is the most common cause of dementia. Optogenetics uses a combination of genetic engineering and light to activate or inhibit specific neurons in the brain.
Conclusion
Activation of glutamatergic neurons by optogenetics in the bilateral DG of an Aβ-injected mouse model of AD improved M1 and M2, but not M3. A single-target optogenetics strategy has spatial limitations; therefore, a multiple targeted optogenetics approach to AD therapy should be explored.
Methods
AAV5-CaMKII-channelrhodopsin-2 (CHR2)-mCherry (Aβ-CHR2 mice) or AAV5-CaMKII-mCherry (Aβ-non-CHR2 mice) was injected into the dentate gyrus (DG) of the bilateral hippocampus of an Aβ1-42-injected mouse model of AD. The novel object recognition test was used to investigate working memory (M1), short-term memory (M2), and long-term memory (M3) after Aβ1-42 injection. Hippocampus tissues were collected for immunohistochemical analysis.
Objective
The objective of the study was to examine the effect of activation of glutamatergic neurons in the hippocampus of mice injected with Aβ1-42 on memory function and biomarkers of neuroinflammation and neuroprotection in the brain to elucidate the clinical utility of optogenetic neuromodulation in AD.
Results
Compared to controls, M1 and M2 were significantly higher in Aβ-CHR2 mice, but there was no significant difference in M3; NeuN and synapsin expression were significantly increased in the DG of Aβ-CHR2 mice, but not in CA1, CA3, the subventricular zone (SVZ), or the entorhinal cortex (ENT); GluR2 and IL-10 expressions were significantly increased, and GFAP expression was significantly decreased, in CA1, CA3, the DG, and the SVZ of Aβ-CHR2 mice, but not in the ENT.