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ORIGINAL ARTICLE
Year : 2017  |  Volume : 37  |  Issue : 4  |  Page : 155-162

Effects of isolation rearing and early antipsychotic intervention on oxidative stress-induced apoptosis and brain-derived neurotrophic factor in hippocampus in a rat model of schizophrenia


1 Department of Psychiatry, Taoyuan Armed Forces General Hospital, Taoyuan 32551, Taipei, Taiwan, Republic of China
2 Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, Republic of China
3 Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan, Republic of China
4 Medical Research Center, Cardinal Tien Hospital, Taipei, Taiwan, Republic of China
5 Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan, Republic of China

Correspondence Address:
Yia-Ping Liu
Department of Physiology and Biophysics, National Defense Medical Center, 161, Minchuan East Road, Section 6, Taipei, Taiwan 114
Republic of China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmedsci.jmedsci_113_16

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Background: Oxidative stress-induced neuronal dysfunction has been considered an essential factor for the development of schizophrenia. However, a longitudinal and causal relation between the impacts of developmental stress and oxidative stress remains unsolved. The present study aimed to examine whether the oxidative stress-relevant dysfunctions of the apoptotic index can be induced in rats of isolation rearing (IR, a rodent model of schizophrenia) and to see if the intervention of antipsychotics can reverse these dysfunctions. Materials and Methods: Pharmacological manipulation (risperidone [RIS] [1 mg/kg/day], olanzapine [OLA] [2.5 mg/kg/day], or saline [SAL] vehicle) was introduced 4 weeks (adolescence) or 8 weeks (young adulthood) after IR (i.e., rats were 7- or 11-week-old). The regime of RIS, OLA, or SAL was continued for 9 weeks. Locomotor activity was employed to validate the IR effect. Rats' hippocampus immediately after sacrifice was removed to measure messenger RNA expression of Bax, Bcl-2, brain-derived neurotrophic factor (BDNF) and the plasma level of nitric oxide (NO). Results: The results showed: (i) IR rats were more hyperactive. (ii) RIS may exert anti-apoptotic effects on IR rats, particularly at their adolescent age (as indexed by increased Bcl-2 and decreased Bax/Bcl-2 ratio). (iii) The therapeutic potential of RIS can be also observed in the change of BDNF in an age-independent manner, in which RIS effectively increased the BDNF level in IR but not social (SOC) rats. (iv) Plasma NO was not altered. Conclusion: The study results support the utility of the IR paradigm in exploring mental disorders with neurodevelopmental origin in which early pharmacological intervention may provide a therapeutic benefit in the overloaded oxidative stress and the dysfunction of BDNF.


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