Long-Term Enhancement of NMDA Receptor Function in Inhibitory Neurons Preferentially Modulates Potassium Channels and Cell Adhesion Molecules

Dan Xia, Xinyang Zhang, Di Deng, Xiaoyan Ma, Samer Masri, Jianzheng Wang, Shaowen Bao, Songnian Hu, Qiang Zhou

Research output: Contribution to journalArticlepeer-review

Abstract

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 Ca2+ channels. In contrast, large differences in cell adhesion molecules and K+ channels were found between Au1 and PrL-PFC in drug-naïve 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.

Original languageEnglish (US)
Article number796179
JournalFrontiers in Pharmacology
Volume12
DOIs
StatePublished - Jan 4 2022

Keywords

  • NMDAR-positive allosteric modulator
  • RNA-seq
  • cell adhesion molecules
  • electrophysiological recording
  • potassium channels

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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