Juvenile bright light exposure ameliorates adult behavioral abnormalities by enhancing neurogenesis in a N-methyl-D-aspartate receptor dysfunction mouse model relevant for cognitive impairment in schizophrenia

Behav Brain Res. 2024 Aug 24:472:115157. doi: 10.1016/j.bbr.2024.115157. Epub 2024 Jul 22.

Abstract

Exposure to light has been demonstrated to stimulate brain regions associated with cognition; however, investigations into its cognitive-enhancing effects have primarily focused on wild-type rodents. This study seeks to elucidate how bright light exposure mitigates cognitive deficits associated with schizophrenia by examining its impact on hippocampal neurogenesis and its potential to alleviate sub-chronic MK-801-induced cognitive impairments in mice. Following three weeks of juvenile bright light exposure (5-8 weeks old), significant increases in proliferating neurons (BrdU+) and immature neurons (DCX+ cells) were observed in the dentate gyrus (DG) and lateral ventricle of MK-801-treated mice. Long-term bright light treatment further promoted the differentiation of BrdU+ cells into immature neurons (BrdU+ DCX+ cells), mature neurons (BrdU+ NeuN+ cells), or astrocytes (BrdU+ GFAP+ cells) in the hippocampal DG. This augmented neurogenesis correlated with the attenuation of sub-chronic MK- 801-induced cognitive deficits, as evidenced by enhancements in Y-maze, novel object recognition (NOR), novel location recognition (NLR), and Morris water maze (MWM) test performances. These findings suggest a promising noninvasive clinical approach for alleviating cognitive impairments associated with neuropsychiatric disorders.

Keywords: Cognitive Impairments; Light Treatment; Neurogenesis; Sub-chronic MK-801.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / physiopathology
  • Cognitive Dysfunction* / therapy
  • Dentate Gyrus / metabolism
  • Disease Models, Animal*
  • Dizocilpine Maleate / pharmacology
  • Doublecortin Protein*
  • Hippocampus / metabolism
  • Light
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis* / physiology
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Schizophrenia* / metabolism
  • Schizophrenia* / physiopathology
  • Schizophrenia* / therapy

Substances

  • Doublecortin Protein
  • Dcx protein, mouse
  • Dizocilpine Maleate
  • Receptors, N-Methyl-D-Aspartate