Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline.

ABSTRACT:

Introduction

Cognitive decline progresses with age, and Nr4a1 has been shown to participate in memory functions. However, the relationship between age-related Nr4a1 reduction and cognitive decline is undefined.

Methods

Nr4a1 expressions were evaluated by quantitative PCR and immunochemical approaches. The cognition of mice was examined by multiple behavioral tests. Patch-clamp experiments were conducted to investigate the synaptic function.

Results

NR4A1 in peripheral blood mononuclear cells decreased with age in humans. In the mouse brain, age-dependent Nr4a1 reduction occurred in the hippocampal CA1. Deleting Nr4a1 in CA1 pyramidal neurons (PyrNs) led to the impairment of cognition and excitatory synaptic function. Mechanistically, Nr4a1 enhanced TrkB expression via

SUBMITTER: Chen J 

PROVIDER: S-EPMC11095431 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature