Piyabhan P, Tingpej P, Duansak N
Division of Physiology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, KlongLuang, Pathumthani, Thailand.
Division of Microbiology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, KlongLuang, Pathumthani, Thailand.
Neuropsychiatr Dis Treat. 2019 May 1;15:1103-1117. doi: 10.2147/NDT.S193222. eCollection 2019.
Decreased gamma-aminobutyric acid (GABA)-ergic neurons in the brain of both schizophrenic patients and animal models indicates that impairment of GABAergic function is implicated in pathophysiology of the disorder. Decreased GABAergic neurotransmission might be also involved in cognitive impairment, which is developed in schizophrenia. Brahmi () could be a new treatment and prevention for this cognitive deficit in schizophrenia by increasing GABAergic neurons to a normal level. The authors aimed to study cognitive-enhancement- and neuroprotective-effects of Brahmi on novel object recognition memory and GABAergic neuronal density, defined by the presence of calcium binding proteins (CBPs; calbindin (CB), parvalbumin (PV), and calretinin (CR)) in a sub-chronic (2 mg/kg, Bid, ip) phencyclidine (PCP) rat model of schizophrenia. In the cognitive-enhancement-effect study rats were assigned to three groups; Group-1: Control, Group-2: PCP-administration, and Group-3: PCP+Brahmi. In the neuroprotective-effect study rats were assigned to three groups; Group-1: Control, Group-2: PCP-administration, and Group-3: Brahmi+PCP. A discrimination ratio (DR) representing cognitive ability was obtained from the novel object recognition task. CB, PV, and CR immunodensity were measured in the prefrontal cortex, striatum, and cornuammonis fields 1-3 (CA1-3) using immunohistochemistry. Reduced DR was found in the PCP group, which occurred alongside reduced CB, PV, and CR in all brain regions except for CR in the striatum and CA1-3 in the cognitive-enhancement-effect study. PCP+Brahmi showed a higher DR score with increased CB in the prefrontal cortex and striatum, increased PV in the prefrontal cortex and CA1-3, and increased CR in the prefrontal cortex. The Brahmi+PCP group showed higher DR score with increased CB in all areas, increased PV in the striatum, and increased CR in the prefrontal cortex and striatum. The present study demonstrated the effects, both partial restoration of cognitive deficit and neuroprotection, of Brahmi, and elucidated its underlying mechanism of actions via increasing GABAergic neurons in a PCP-induced schizophrenic-like model.
精神分裂症患者及动物模型大脑中γ-氨基丁酸（GABA）能神经元数量减少，这表明GABA能功能受损与该疾病的病理生理学有关。GABA能神经传递减少可能也与精神分裂症中出现的认知障碍有关。婆罗门参（Brahmi）可能是一种新的治疗和预防精神分裂症认知缺陷的方法，它可将GABA能神经元数量增加到正常水平。作者旨在研究婆罗门参对新型物体识别记忆和GABA能神经元密度的认知增强和神经保护作用，GABA能神经元密度通过钙结合蛋白（CBPs；钙结合蛋白（CB）、小白蛋白（PV）和钙视网膜蛋白（CR））的存在来定义，研究采用亚慢性（2 mg/kg，每日两次，腹腔注射）苯环己哌啶（PCP）诱导的精神分裂症大鼠模型。在认知增强作用研究中，大鼠被分为三组：第1组：对照组；第2组：给予PCP组；第3组：PCP+婆罗门参组。在神经保护作用研究中，大鼠也被分为三组：第1组：对照组；第2组：给予PCP组；第3组：婆罗门参+PCP组。通过新型物体识别任务获得代表认知能力的辨别率（DR）。使用免疫组织化学方法测量前额叶皮质、纹状体和海马1-3区（CA1-3）的CB、PV和CR免疫密度。在认知增强作用研究中，PCP组的DR降低，同时除纹状体中的CR和CA1-3外，所有脑区的CB、PV和CR均减少。PCP+婆罗门参组的DR得分更高，前额叶皮质和纹状体中的CB增加，前额叶皮质和CA1-3中的PV增加，前额叶皮质中的CR增加。婆罗门参+PCP组的DR得分更高，所有区域的CB增加，纹状体中的PV增加，前额叶皮质和纹状体中的CR增加。本研究证明了婆罗门参具有部分恢复认知缺陷和神经保护的作用，并通过在PCP诱导的精神分裂症样模型中增加GABA能神经元阐明了其潜在作用机制。
