Voluntary exercise improves cognitive deficits in female dominant-negative DISC1 transgenic mouse model of neuropsychiatric disorders

World J Biol Psychiatry. 2019 Mar;20(3):243-252. doi: 10.1080/15622975.2017.1323118. Epub 2017 Jun 8.


Objectives: Physical exercise has gained increasing interest as a treatment modality that improves prognosis in psychiatric patients. The disrupted in schizophrenia 1 (DISC1) gene is a candidate gene for major mental illness. In this study, we aimed to determine whether voluntary wheel running can improve cognitive deficits of dominant-negative DISC1 transgenic mice (DN-DISC1).

Methods: DN-DISC1 and control mice (10-week-old male and female) were placed for 14 days in a cage with or without access to a running wheel. Two weeks later, mice underwent behavioural tests evaluating cognition and social approach and recognition.

Results: Voluntary exercise improved performance in the novel object recognition test, restored the impairment in spatial memory in the Y maze, and reversed the deficit in social recognition memory in DN-DISC1 females. DN-DISC1 males did not exhibit behavioural deficits at baseline. Tissue analysis revealed that exercise induced a significant increase in hippocampal expression of doublecortin (DCX), brain-derived neurotrophic factor (BDNF) and cannabinoid receptor type 1 (CB1R) only in DN-DISC1 females.

Conclusions: Voluntary exercise is beneficial in attenuating cognitive deficits observed in a rodent model relevant for neuropsychiatric disorders. The data add a preclinical aspect to the accumulating clinical data supporting the incorporation of physical exercise to patients' care.

Keywords: DISC1; animal model; exercise; neurogenesis; recognition memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / therapy*
  • Disease Models, Animal
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Female
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Humans
  • Male
  • Maze Learning*
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Neuropeptides / metabolism
  • Physical Conditioning, Animal*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Running
  • Schizophrenia / metabolism
  • Schizophrenia / therapy*


  • Brain-Derived Neurotrophic Factor
  • DCX protein, human
  • Dcx protein, mouse
  • Disc1 protein, mouse
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Receptor, Cannabinoid, CB1