| First Author | Yamamoto K | Year | 2015 |
| Journal | Cell Rep | Volume | 11 |
| Issue | 6 | Pages | 859-865 |
| PubMed ID | 25937280 | Mgi Jnum | J:228470 |
| Mgi Id | MGI:5707128 | Doi | 10.1016/j.celrep.2015.04.017 |
| Citation | Yamamoto K, et al. (2015) Chronic optogenetic activation augments abeta pathology in a mouse model of Alzheimer disease. Cell Rep 11(6):859-65 |
| abstractText | In vivo experimental evidence indicates that acute neuronal activation increases Abeta release from presynaptic terminals, whereas long-term effects of chronic synaptic activation on Abeta pathology remain unclear. To address this issue, we adopted optogenetics and transduced stabilized step-function opsin, a channelrhodopsin engineered to elicit a long-lasting neuronal hyperexcitability, into the hippocampal perforant pathway of APP transgenic mice. In vivo microdialysis revealed a approximately 24% increase in the hippocampal interstitial fluid Abeta42 levels immediately after acute light activation. Five months of chronic optogenetic stimulation increased Abeta burden specifically in the projection area of the perforant pathway (i.e., outer molecular layer of the dentate gyrus) of the stimulated side by approximately 2.5-fold compared with that in the contralateral side. Epileptic seizures were observed during the course of chronic stimulation, which might have partly contributed to the Abeta pathology. These findings implicate functional abnormalities of specific neuronal circuitry in Abeta pathology and Alzheimer disease. |
