A Special Extract ofBacopa monnieri(CDRI-08)-Restored Memory in CoCl2-Hypoxia Mimetic Mice Is Associated with Upregulation ofFmr-1Gene Expression in Hippocampus

Abstract

Fragile X mental retardation protein (FMRP) is a neuronal translational repressor and has been implicated in learning, memory, and cognition. However, the role ofBacopa monnieriextract (CDRI-08) in enhancing cognitive abilities in hypoxia-induced memory impairment viaFmr-1gene expression is not known. Here, we have studied effects of CDRI-08 on the expression ofFmr-1gene in the hippocampus of well validated cobalt chloride (CoCl2)-induced hypoxia mimetic mice and analyzed the data with alterations in spatial memory. Results obtained from Morris water maze test suggest that CoCl2treatment causes severe loss of spatial memory and CDRI-08 is capable of reversing it towards that in the normal control mice. Our semiquantitative RT-PCR, Western blot, and immunofluorescence microscopic data reveal that CoCl2-induced hypoxia significantly upregulates the expression of Hif-1αand downregulates theFmr-1expression in the hippocampus, respectively. Further, CDRI-08 administration reverses the memory loss and this is correlated with significant downregulation of Hif-1αand upregulation ofFmr-1expression. Our data are novel and may provide mechanisms of hypoxia-induced impairments in the spatial memory and action of CDRI-08 in the recovery of hypoxia led memory impairment involvingFmr-1gene encoded protein called FMRP.