AUTHOR=Cui Xiaorui , Zhang Feng , Zhang Hui , Huang Xi , Wang Kewei , Huang Ting , Yang Xifei , Zou Liangyu
TITLE=Neuroprotective Effect of Optogenetics Varies With Distance From Channelrhodopsin-2 Expression in an Amyloid-β-Injected Mouse Model of Alzheimer’s Disease
JOURNAL=Frontiers in Neuroscience
VOLUME=14
YEAR=2020
URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.583628
DOI=10.3389/fnins.2020.583628
ISSN=1662-453X
ABSTRACT=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.
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.
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.
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.
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.