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Neuroprotective Effects of Bacopa monnieri (Brahmi) on Novel Object Recognition and NMDAR1 Immunodensity in the Prefrontal Cortex, Striatum and Hippocampus of Sub-Chronic Phencyclidine Rat Model of Schizophrenia

Pritsana Piyabhan PhD*, Thanitsara Wetchateng PhD*

Affiliation : * Department of Preclinical Science, Faculty of Medicine, Thammasat University, Rangsit Campus, Klong Luang, Pathumthani, Thailand

Background : Cognitive impairment is a major problem, which eventually develops in schizophrenia. It contributes to the patients’ functional disability and cannot be attenuated by antipsychotic drugs. Bacopa monnieri (Brahmi), a neuroprotective herbal medicine in the elderly, might be a novel neuroprotective agent for prevention of cognitive deficit in schizophrenia.
Objective : To study neuroprotective effects of Brahmi on novel object recognition task and cerebral glutamate/N-methyl-D- aspartate receptor subtype 1 (NMDAR1) immunodensity in sub-chronic phencyclidine (PCP) rat model of schizophrenia. Material and Method: Rats were assigned to three groups; Group-A: Control, Group-B: PCP administration and Group- C: Brahmi + PCP. Discrimination ratio (DR) representing cognitive ability was obtained from novel object recognition task. NMDAR1 immunodensity was measured in prefrontal cortex, striatum, cornu ammonis fields 1 (CA1) and 2/3 (CA2/3) and dentate gyrus (DG) using immunohistochemistry.
Results : DR was significantly reduced in PCP group compared with control. This occurred alongside NMDAR1 up-regulation in CA2/3 and DG, but not in prefrontal cortex, striatum or CA1. Brahmi + PCP group showed an increased DR score up to normal which occurred alongside a significantly decreased NMDAR1 immunodensity in CA2/3 and DG compared with PCP group.
Conclusion : Cognitive deficit observed in rats receiving PCP was mediated by NMDAR1 up-regulation in CA2/3 and DG. Interestingly, receiving Brahmi before PCP administration can restore this cognitive deficit by decreasing NMDAR1 in these brain areas. Therefore, Brahmi could be a novel neuroprotective agent for the prevention of cognitive deficit in schizophrenia.

Keywords : Brahmi, Schizophrenia, Animal model, Novel object recognition, NMDAR1


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