| First Author | Xia D | Year | 2021 |
| Journal | Front Pharmacol | Volume | 12 |
| Pages | 796179 | PubMed ID | 35058780 |
| Mgi Jnum | J:358716 | Mgi Id | MGI:6857111 |
| Doi | 10.3389/fphar.2021.796179 | Citation | Xia D, et al. (2021) Long-Term Enhancement of NMDA Receptor Function in Inhibitory Neurons Preferentially Modulates Potassium Channels and Cell Adhesion Molecules. Front Pharmacol 12:796179 |
| abstractText | Effectively enhancing the activity of inhibitory neurons has great therapeutic potentials since their reduced function/activity has significant contributions to pathology in various brain diseases. We showed previously that NMDAR positive allosteric modulator GNE-8324 and M-8324 selectively increase NMDAR activity on the inhibitory neurons and elevates their activity in vitro and in vivo. Here we examined the impact of long-term administering M-8324 on the functions and transcriptional profiling of parvalbumin-containing neurons in two representative brain regions, primary auditory cortex (Au1) and prelimbic prefrontal cortex (PrL-PFC). We found small changes in key electrophysiological parameters and RNA levels of neurotransmitter receptors, Na(+) and Ca(2+) channels. In contrast, large differences in cell adhesion molecules and K(+) channels were found between Au1 and PrL-PFC in drug-naive mice, and differences in cell adhesion molecules became much smaller after M-8324 treatment. There was also minor impact of M-8324 on cell cycle and apoptosis, suggesting a fine safety profile. |
