| First Author | Ferreira S | Year | 2020 |
| Journal | J Neurosci Res | Volume | 98 |
| Issue | 10 | Pages | 1905-1932 |
| PubMed ID | 32557778 | Mgi Jnum | J:311338 |
| Mgi Id | MGI:6728192 | Doi | 10.1002/jnr.24672 |
| Citation | Ferreira S, et al. (2020) Amyloidosis is associated with thicker myelin and increased oligodendrogenesis in the adult mouse brain. J Neurosci Res 98(10):1905-1932 |
| abstractText | In Alzheimer's disease, amyloid plaque formation is associated with the focal death of oligodendrocytes and soluble amyloid beta impairs the survival of oligodendrocytes in vitro. However, the response of oligodendrocyte progenitor cells (OPCs) to early amyloid pathology remains unclear. To explore this, we performed a histological, electrophysiological, and behavioral characterization of transgenic mice expressing a pathological form of human amyloid precursor protein (APP), containing three single point mutations associated with the development of familial Alzheimer's disease (PDGFB-APP(Sw.Ind) , also known as J20 mice). PDGFB-APP(Sw.Ind) transgenic mice had impaired survival from weaning, were hyperactive by 2 months of age, and developed amyloid plaques by 6 months of age, however, their spatial memory remained intact over this time course. Hippocampal OPC density was normal in P60-P180 PDGFB-APP(Sw.Ind) transgenic mice and, by performing whole-cell patch-clamp electrophysiology, we found that their membrane properties, including their response to kainate (100 microM), were largely normal. However, by P100, the response of hippocampal OPCs to GABA was elevated in PDGFB-APP(Sw.Ind) transgenic mice. We also found that the nodes of Ranvier were shorter, the paranodes longer, and the myelin thicker for hippocampal axons in young adult PDGFB-APP(Sw.Ind) transgenic mice compared with wildtype littermates. Additionally, oligodendrogenesis was normal in young adulthood, but increased in the hippocampus, entorhinal cortex, and fimbria of PDGFB-APP(Sw.Ind) transgenic mice as pathology developed. As the new oligodendrocytes were not associated with a change in total oligodendrocyte number, these cells are likely required for cell replacement. |
