title: Standardised extract of Bacopa monniera (CDRI-08) improves contextual fear memory by differentially regulating the activity of histone acetylation and protein phosphatases (PP1α, PP2A) in hippocampus.
abstract: Contextual fear conditioning is a paradigm for investigating cellular mechanisms involved in hippocampus-dependent memory. Earlier, we showed that standardised extract of Bacopa monniera (CDRI-08) improves hippocampus-dependent learning in postnatal rats by elevating the level of serotonin (5-hydroxytryptamine, 5-HT), activate 5-HT3A receptors, and cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein. In this study, we have further examined the molecular mechanism of CDRI-08 in hippocampus-dependent memory and compared to the histone deacetylase (HDACs) inhibitor sodium butyrate (NaB). To assess the hippocampus-dependent memory, wistar rat pups were subjected to contextual fear conditioning (CFC) following daily (postnatal days 15-29) administration of vehicle solution (0.5 % gum acacia + 0.9 % saline)/CDRI-08 (80 mg/kg, p.o.)/NaB (1.2 g/kg in PBS, i.p.). CDRI-08/NaB treated group showed enhanced freezing behavior compared to control group when re-exposed to the same context. Administration of CDRI-08/NaB resulted in activation of extracellular signal-regulated kinase ERK/CREB signaling cascade and up-regulation of p300, Ac-H3 and Ac-H4 levels, and down-regulation of HDACs (1, 2) and protein phosphatases (PP1α, PP2A) in hippocampus following CFC. This would subsequently result in an increased brain-derived neurotrophic factor (Bdnf) (exon IV) mRNA in hippocampus. Altogether, our results indicate that CDRI-08 enhances hippocampus-dependent contextual memory by differentially regulating histone acetylation and protein phosphatases in hippocampus.
authors.affiliation: Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, 620024, India.
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Preethi
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Singh
authors.forename: Jois Shreyas
authors.initials: JS
authors.lastname: Venkataraman
authors.forename: Koilmani Emmanuvel
authors.initials: KE
authors.lastname: Rajan
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D034681:Bacopa; D005239:Fear / Q000187:drug effects* / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000627:therapeutic use*; D028321:Plant Preparations / Q000494:pharmacology*; D017208:Rats, Wistar
chemical_list: D006657:Histones; D028321:Plant Preparations; D010749:Phosphoprotein Phosphatases