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

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posted on 08.06.2017 by Hadar Segal-Gavish, Ran Barzilay, Ofri Rimoni, Daniel Offen

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.

Funding

This study was supported in part by the National Institute of Psychobiology in Israel [Grant no. 0601564281].

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