Cognitive enhancement effects of Bacopa monnieri (Brahmi) on novel object recognition and VGLUT1 density in the prefrontal cortex, striatum, and hippocampus of sub-chronic phencyclidine rat model of schizophrenia

Abstract

Background: Decreased vesicular glutamate transporter type 1 (VGLUT1) in schizophrenic brain indicates the deficit of glutamatergic function, which may produce cognitive impairment in the patients. Brahmi might be a novel therapeutic agent for the cognitive deficit treatment in schizophrenia by changing cerebral VGLUT1 density.

Objective: To study effects of Brahmi on attenuation at cognitive deficit and cerebral VGLUT1 density in sub-chronic phencyclidine (PCP) rat model of schizophrenia.

Material and method: Rats were administered PCP or vehicle. Half of the PCP-group was treated with Brahmi. Discrimination ratio (DR) representing cognitive ability was obtained from novel object recognition test. VGLUT1 density was measured in prefrontal cortex, striatum, cornu ammonis fields 1 (CA1) and 2/3 (CA2/3) of hippocampus and dentate gyrus (DG) using western blot and immunohistochemistry.

Results: DR in PCP-group was significantly decreased compared with control. This occurred alongside reduced VGLUT1 in prefrontal cortex, striatum, CA1 and CA2/3. PCP with Brahmi showed a significant increase in DR score compared with PCP alone. This occurred alongside significant increase in VGLUT1 in CA1 and CA2/3.

Conclusion: Cognitive deficit observed in PCP-administered rats was mediated by VGLUT1 reduction in prefrontal cortex, striatum, CA1 and CA2/3. Interestingly, Brahmi could recover this cognitive deficit by increasing VGLUT1 in CA1 and CA2/3 to normal.