Phasic and tonic type A γ-Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal Neurons

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...

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Main Authors: Janardhan Prasad Bhattarai, Seong Kyu Han
Format: Article
Language:English
Published: Elsevier 2014-01-01
Series:Journal of Ayurveda and Integrative Medicine
Subjects:
Online Access:http://www.jaim.in/article.asp?issn=0975-9476;year=2014;volume=5;issue=4;spage=216;epage=222;aulast=
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author Janardhan Prasad Bhattarai
Seong Kyu Han
author_facet Janardhan Prasad Bhattarai
Seong Kyu Han
author_sort Janardhan Prasad Bhattarai
collection DOAJ
description 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 GABA A receptor antagonist, bicuculline- 20 μM (BIC) (BIC: -1.46 ± 1.4 pA, P < 0.001), but only partially by synaptic GABA A receptor blocker gabazine (1 μM) (GBZ: -18.26 ± 4.70 pA, P < 0.01). Conclusion: These results suggest that WS acts on synaptic/extrasynaptic GABA A receptors and may play an important role in the process of memory and neuroprotection via activation of synaptic and extrasynaptic GABA A receptors.
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spelling doaj.art-5e82d52538564fb4abf46e502cd4b13a2022-12-21T18:12:18ZengElsevierJournal of Ayurveda and Integrative Medicine0975-94762014-01-015421622210.4103/0975-9476.146541Phasic and tonic type A γ-Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal NeuronsJanardhan Prasad BhattaraiSeong Kyu HanBackground: 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 GABA A receptor antagonist, bicuculline- 20 μM (BIC) (BIC: -1.46 ± 1.4 pA, P < 0.001), but only partially by synaptic GABA A receptor blocker gabazine (1 μM) (GBZ: -18.26 ± 4.70 pA, P < 0.01). Conclusion: These results suggest that WS acts on synaptic/extrasynaptic GABA A receptors and may play an important role in the process of memory and neuroprotection via activation of synaptic and extrasynaptic GABA A receptors.http://www.jaim.in/article.asp?issn=0975-9476;year=2014;volume=5;issue=4;spage=216;epage=222;aulast=GABA A receptorshippocampal CA1 neuronspatch clamp techniqueWithania somnifera
spellingShingle Janardhan Prasad Bhattarai
Seong Kyu Han
Phasic and tonic type A γ-Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal Neurons
Journal of Ayurveda and Integrative Medicine
GABA A receptors
hippocampal CA1 neurons
patch clamp technique
Withania somnifera
title Phasic and tonic type A γ-Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal Neurons
title_full Phasic and tonic type A γ-Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal Neurons
title_fullStr Phasic and tonic type A γ-Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal Neurons
title_full_unstemmed Phasic and tonic type A γ-Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal Neurons
title_short Phasic and tonic type A γ-Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal Neurons
title_sort phasic and tonic type a γ aminobutryic acid receptor mediated effect of withania somnifera on mice hippocampal ca1 pyramidal neurons
topic GABA A receptors
hippocampal CA1 neurons
patch clamp technique
Withania somnifera
url http://www.jaim.in/article.asp?issn=0975-9476;year=2014;volume=5;issue=4;spage=216;epage=222;aulast=
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AT seongkyuhan phasicandtonictypeagaminobutryicacidreceptormediatedeffectofwithaniasomniferaonmicehippocampalca1pyramidalneurons