Effect of chronic olanzapine treatment on nerve growth factor and brain-derived neurotrophic factor in the rat brain
Effect of chronic olanzapine treatment on nerve growth factor and brain-derived neurotrophic factor in the rat brain
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DOI：
10.1016/j.euroneuro.2004.11.005
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发表时间：
2005-05-01
影响因子：
5.6
通讯作者：
Mathé, AA
中科院分区：
文献类型：
--
作者：
Angelucci, F;Aloe, L;Mathé, AA
神经生长因子（NGF）和脑源性神经营养因子（BDNF）是参与神经元存活、轴突生长和突触形成的蛋白质。最近的观察表明，典型和非典型抗精神病药物治疗影响大鼠脑中的NGF和BDNF水平。非典型抗精神病药奥氮平的副作用发生率较低，如锥体外系和抗胆碱能症状。由于NGF和BDNF参与中枢神经系统（CNS）中胆碱能、多巴胺能和多巴胺能神经元的调节，我们假设长期奥氮平治疗将影响大鼠脑中NGF和BDNF的分布。为了验证这一假设，我们以3和15 mg/kg体重的剂量在饮用水中给予奥氮平29天，并测量Wistar大鼠脑中NGF和BDNF的水平。奥氮平可增加海马、枕叶皮质和下丘脑中的NGF。相反，奥氮平降低海马和额叶皮质中的BDNF。虽然这些发现的意义尚不清楚，但一个启发性的假设是奥氮平的临床效果和有利的副作用特征部分是由神经营养因子介导的。(c)2004年Elsevier B. V.和ECNP。All rights reserved.
Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are proteins involved in neuronal survival, neurite outgrowth and synapse formation. Recent observations suggest that treatment with typical and atypical antipsychotic drugs affect NGF and BDNF levels in the rat brain. The atypical antipsychotic olanzapine has a low incidence of side effects, such as extrapyramidal and anticholinergic symptoms. Since NGF and BDNF are involved in the regulation of cholinergic, dopaminergic and serotonergic neurons in the central nervous system (CNS) we hypothesized that chronic olanzapine treatment will influence the distribution of NGF and BDNF in the rat brain. To test this hypothesis we administered olanzapine for 29 days in the drinking water at the doses of 3 and 15 mg/kg body weight and measured the levels of NGF and BDNF in the brain of Wistar rats. Olanzapine increased NGF in the hippocampus, occipital cortex and hypothalamus. In contrast, olanzapine decreased BDNF in the hippocampus and frontal cortex. Although the significance of these findings is not clear, a heuristic hypothesis is that olanzapine's clinical effects and a favorable side effect profile are in part mediated by neurotrophins. (c) 2004 Elsevier B.V. and ECNP. All rights reserved.