| First Author | Back MK | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 12 | PubMed ID | 34208315 |
| Mgi Jnum | J:311249 | Mgi Id | MGI:6751172 |
| Doi | 10.3390/ijms22126298 | Citation | Back MK, et al. (2021) Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors. Int J Mol Sci 22(12) |
| abstractText | Onset and progression of Alzheimer's disease (AD) pathophysiology differs between brain regions. The neocortex, for example, is a brain region that is affected very early during AD. NMDA receptors (NMDARs) are involved in mediating amyloid beta (Abeta) toxicity. NMDAR expression, on the other hand, can be affected by Abeta. We tested whether the high vulnerability of neocortical neurons for Abeta-toxicity may result from specific NMDAR expression profiles or from a particular regulation of NMDAR expression by Abeta. Electrophysiological analyses suggested that pyramidal cells of 6-months-old wildtype mice express mostly GluN1/GluN2A NMDARs. While synaptic NMDAR-mediated currents are unaltered in 5xFAD mice, extrasynaptic NMDARs seem to contain GluN1/GluN2A and GluN1/GluN2A/GluN2B. We used conditional GluN1 and GluN2B knockout mice to investigate whether NMDARs contribute to Abeta-toxicity. Spine number was decreased in pyramidal cells of 5xFAD mice and increased in neurons with 3-week virus-mediated Abeta-overexpression. NMDARs were required for both Abeta-mediated changes in spine number and functional synapses. Thus, our study gives novel insights into the Abeta-mediated regulation of NMDAR expression and the role of NMDARs in Abeta pathophysiology in the somatosensory cortex. |
