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水飞蓟宾(Brahmi)通过增加亚慢性苯环利定诱导的精神分裂症大鼠模型前额叶皮质中VGLUT2免疫密度来增强认知功能并预防认知障碍。

Bacopa monnieri (Brahmi) Enhanced Cognitive Function and Prevented Cognitive Impairment by Increasing VGLUT2 Immunodensity in Prefrontal Cortex of Sub-Chronic Phencyclidine Rat Model of Schizophrenia.

作者信息

Piyabhan Pritsana, Wetchateng Thanitsara

出版信息

J Med Assoc Thai. 2015 Apr;98 Suppl 3:S7-15.

Abstract

BACKGROUND

Glutamatergic hypofunction is affected in schizophrenia. The decrement ofpresynaptic glutamatergic marker remarkably vesicular glutamate transporter type 1 (VGLUT1) indicates the deficit ofglutamatergic and cognitive function in schizophrenic brain. However there have been afew studies in VGLUT2. Brahmi, a traditional herbal medicine, might be a new frontier of cognitive deficit treatment and prevention in schizophrenia by changing cerebral VGLUT2 density.

OBJECTIVE

To study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition task and cerebral VGLUT2 immunodensity in sub-chronic phencyclidine (PCP) rat model of schizophrenia.

MATERIAL AND METHOD

Cognitive enhancement effect study; rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: PCP + Brahmi. Neuroprotective effect study; rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: Brahmi + PCP Discrimination ratio (DR) representing cognitive ability was obtained from novel object recognition task. VGLUT2 immunodensity was measured in prefrontal cortex, striatum, cornu ammonis fields 1 (CA1) and 2/3 (CA2/3) of hippocampus using immunohistochemistry.

RESULTS

DR was significantly reduced in PCP group compared with control. This occurred alongside VGLUT2 reduction in prefrontal cortex, but not in striatum, CA1 or CA2/3. Both PCP + Brahmi and Brahmi + PCP groups showed an increased DR score up to normal, which occurred alongside a significantly increased VGLUT2 immunodensity in the prefrontal cortex, compared with PCP group.

CONCLUSION

The decrement of VGLUT2 density in prefrontal cortex resulted in cognitive deficit in rats receiving PCP. Interestingly, receiving Brahmi after PCP administration can restore this cognitive deficit by increasing VGLUT2 density in prefrontal cortex. This investigation is defined as Brahmi's cognitive enhancement effect. Additionally, receiving Brahmi before PCP administration can also prevent cognitive impairment by elevating VGLUT2 density in prefrontal cortex. This observation indicates neuroprotective effect of Brahmi. Therefore, Brahmi could be a new frontier of restoration and prevention of cognitive deficit in schizophrenia.

摘要

背景

精神分裂症患者存在谷氨酸能功能减退。突触前谷氨酸能标志物尤其是囊泡谷氨酸转运体1(VGLUT1)的减少表明精神分裂症患者大脑中谷氨酸能和认知功能存在缺陷。然而,关于VGLUT2的研究较少。传统草药婆罗米可能通过改变大脑VGLUT2密度成为精神分裂症认知缺陷治疗和预防的新前沿。

目的

研究婆罗米对精神分裂症亚慢性苯环己哌啶(PCP)大鼠模型新颖物体识别任务和大脑VGLUT2免疫密度的认知增强和神经保护作用。

材料与方法

认知增强作用研究;将大鼠分为三组;第1组:对照组,第2组:给予PCP组,第3组:PCP + 婆罗米组。神经保护作用研究;将大鼠分为三组;第1组:对照组,第2组:给予PCP组,第3组:婆罗米 + PCP组。从新颖物体识别任务中获得代表认知能力的辨别率(DR)。使用免疫组织化学法测量前额叶皮质、纹状体、海马的1区(CA1)和2/3区(CA2/3)的VGLUT2免疫密度。

结果

与对照组相比,PCP组的DR显著降低。这与前额叶皮质中VGLUT2的减少同时发生,但在纹状体、CA1或CA2/3中未出现。PCP + 婆罗米组和婆罗米 + PCP组的DR评分均升高至正常水平,与PCP组相比,这与前额叶皮质中VGLUT2免疫密度显著增加同时发生。

结论

前额叶皮质中VGLUT2密度的降低导致接受PCP的大鼠出现认知缺陷。有趣的是,在给予PCP后给予婆罗米可以通过增加前额叶皮质中VGLUT2的密度来恢复这种认知缺陷。这一研究被定义为婆罗米的认知增强作用。此外,在给予PCP前给予婆罗米也可以通过提高前额叶皮质中VGLUT2的密度来预防认知障碍。这一观察结果表明婆罗米具有神经保护作用。因此,婆罗米可能成为精神分裂症认知缺陷恢复和预防的新前沿。

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