Phasic and Tonic Type A γ-Aminobutryic Acid Receptor Mediated Effect of Withania Somnifera on Mice Hippocampal CA1 Pyramidal Neurons

Overview

Journal J Ayurveda Integr Med

Publisher Elsevier

Date 2015 Jan 28

PMID 25624695

Citations 3

Authors

Janardhan Prasad Bhattarai

Seong Kyu Han

Affiliations

Soon will be listed here.

Abstract

Background: In Nepali and Indian system of traditional medicine, Withania somnifera (WS) is considered as a rejuvenative medicine to maintain physical and mental health and has also been shown to improve memory consolidation.

Objective: In this study, a methanolic extract of WS (mWS) was applied on mice hippocampal CA1 neurons to identify the receptors activated by the WS.

Materials And Methods: The whole cell patch clamp recordings were performed on CA1 pyramidal neurons from immature mice (7-20 postnatal days). The cells were voltage clamped at -60 mV. Extract of WS root were applied to identify the effect of mWS.

Results: The application of mWS (400 ng/μl) induced remarkable inward currents (-158.1 ± 28.08 pA, n = 26) on the CA1 pyramidal neurons. These inward currents were not only reproducible but also concentration dependent. mWS-induced inward currents remained persistent in the presence of amino acid receptor blocking cocktail (AARBC) containing blockers for the ionotropic glutamate receptors, glycine receptors and voltage-gated Na(+) channel (

Control: -200.3 ± 55.42 pA, AARBC: -151.5 ± 40.58 pA, P > 0.05) suggesting that most of the responses by mWS are postsynaptic events. Interestingly, these inward currents were almost completely blocked by broad GABAA receptor antagonist, bicuculline- 20 μM (BIC) (BIC: -1.46 ± 1.4 pA, P < 0.001), but only partially by synaptic GABAA receptor blocker gabazine (1 μM) (GBZ: -18.26 ± 4.70 pA, P < 0.01).

Conclusion: These results suggest that WS acts on synaptic/extrasynaptic GABAA receptors and may play an important role in the process of memory and neuroprotection via activation of synaptic and extrasynaptic GABAA receptors.

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