Period3 modulates the NAD⁺-SIRT3 axis to alleviate depression-like behaviour by enhancing NAMPT activity in mice.

ABSTRACT:

Introduction

PERIOD (PER)3 deficiency is associated with depression-like behaviors, but the underlying mechanisms remain unclear.

Objectives

This study aims to elucidate the role and mechanism of PER3 in regulating depression-like behaviors in mice.

Methods

Depression-like behaviors were assessed using the sucrose preference test, tail suspension test, and forced swimming test. Metabolomic analysis was conducted on hippocampal tissues from Per3 knockout mice using chromatography-mass spectrometry. The regulatory role of PER3 on the expression of nicotinamide phosphoribosyltransferase (Nampt) was investigated through co-immunoprecipitation and chromatin immunoprecipitation assays.

Results

Metabolomic analysis revealed that Per3 deficiency disrupts mitochondrial

SUBMITTER: Xie X 

PROVIDER: S-EPMC12627864 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature