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

Szu‑Nian Yang ； Yu‑Yin Yang ； Fang‑Jung Wan ； Chuen‑Lin Huang ； Yia‑Ping Liu

《Journal of Medical Sciences》 37卷4期 (2017/08) Pp. 155-162

https://doi.org/10.4103/jmedsci.jmedsci_113_16

摘要

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.

關鍵字

Brain‑derived neurotrophic factor ； early antipsychotic intervention ； isolation rearing ； oxidative stress ； schizophrenia