Optogenetics-induced activation of glutamate receptors improves memory function in mice with Alzheimer’s disease
摘要
Abstract
Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-pos-itive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate recep-tor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.关键词
nerve regeneration/Alzheimer’s disease/amyloid-β1–42/dentate gyrus/channelrhodopsin-2/glutamate receptors/memory/neuroinfammation/novel object recognition/immunohistochemistry/western blot assay/neural regenerationKey words
nerve regeneration/Alzheimer’s disease/amyloid-β1–42/dentate gyrus/channelrhodopsin-2/glutamate receptors/memory/neuroinfammation/novel object recognition/immunohistochemistry/western blot assay/neural regeneration引用本文复制引用
KeWei Wang,XiaoLin Ye,Ting Huang,XiFei Yang,LiangYu Zou..Optogenetics-induced activation of glutamate receptors improves memory function in mice with Alzheimer’s disease[J].中国神经再生研究（英文版）,2019,14(12):2147-2155,9.基金项目
This study was supported by the National Natural Science Foundation of China, No. 81171191 (to LYZ) （to LYZ）
the Shenzhen Special Fund Project on Strategic Emerging Industry Development of China, No. JCYJ20160422170522075 (to LYZ) （to LYZ）
the Shenzhen Healthcare Research Project of China, No. 201601015 (to LYZ). Financial support: This study was supported by the National Natural Science Foundation of China, No. 81171191 (to LYZ) （to LYZ）
the Shenzhen Special Fund Project on Strategic Emerging Industry Development of China, No. JCYJ20160422170522075 (to LYZ) （to LYZ）
the Shenzhen Healthcare Research Project of China, No. 201601015 (to LYZ). Funders had no involvement in the study design （to LYZ）
data collection, analysis, and interpreta-tion （）
paper writing （）
or decision to submit the paper for publication. （）
