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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

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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.

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Acknowledgments

We thank the editor and anonymous reviewers for their critical comments on improvement of the manuscript. KER is thankful to Lumen Marketing Company (Chennai, India) for providing the standardised B. monniera extract (CDRI-08).

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Authors and Affiliations

  1. Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, 620024, India

    Jayakumar Preethi & Koilmani Emmanuvel Rajan

  2. Laboratories for CNS Disorder, Learning & Memory, Division of Pharmacology, Central Drug Research Institute, Lucknow, 226001, India

    Hemant K. Singh

  3. Department of Animal Physiology/Neurobiology, Zoological Institute, University of Cologne, 50674, Colonge, Germany

    Jois Shreyas Venkataraman

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  1. Jayakumar Preethi
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Preethi, J., Singh, H.K., Venkataraman, J.S. et al. 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. Cell Mol Neurobiol 34, 577–589 (2014). https://doi.org/10.1007/s10571-014-0042-0

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