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      Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

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          Abstract

          Abstact
          Background

          Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue.

          Methods

          In the present study, alterations of the general GABA, GABA A and GABA B receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated.

          Results

          Scatchard analysis of [ 3H]GABA, [ 3H]bicuculline and [ 3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in B max (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABA Aά1, GABA , GABA , GABA B and GAD where down regulated (P < 0.001) in epileptic rats. GABA Aά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance.

          Conclusions

          Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

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          Most cited references44

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          Epilepsy.

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            Epilepsy, E/I Balance and GABAA Receptor Plasticity

            GABAA receptors mediate most of the fast inhibitory transmission in the CNS. They form heteromeric complexes assembled from a large family of subunit genes. The existence of multiple GABAA receptor subtypes differing in subunit composition, localization and functional properties underlies their role for fine-tuning of neuronal circuits and genesis of network oscillations. The differential regulation of GABAA receptor subtypes represents a major facet of homeostatic synaptic plasticity and contributes to the excitation/inhibition (E/I) balance under physiological conditions and upon pathological challenges. The purpose of this review is to discuss recent findings highlighting the significance of GABAA receptor heterogeneity for the concept of E/I balance and its relevance for epilepsy. Specifically, we address the following issues: (1) role for tonic inhibition, mediated by extrasynaptic GABAA receptors, for controlling neuronal excitability; (2) significance of chloride ion transport for maintenance of the E/I balance in adult brain; and (3) molecular mechanisms underlying GABAA receptor regulation (trafficking, posttranslational modification, gene transcription) that are important for homoeostatic plasticity. Finally, the relevance of these findings is discussed in light of the involvement of GABAA receptors in epileptic disorders, based on recent experimental studies of temporal lobe epilepsy (TLE) and absence seizures and on the identification of mutations in GABAA receptor subunit genes underlying familial forms of epilepsy.
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              Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments.

              Glutamate and gamma-amino butyric acid (GABA) systems are emerging as targets for development of medications for mood disorders. There is increasing preclinical and clinical evidence that antidepressant drugs directly or indirectly reduce N-methyl-D-aspartate glutamate receptor function. Drugs that reduce glutamatergic activity or glutamate receptor-related signal transduction may also have antimanic effects. Recent studies employing magnetic resonance spectroscopy also suggest that unipolar, but not bipolar, depression is associated with reductions in cortical GABA levels. Antidepressant and mood-stabilizing treatments also appear to raise cortical GABA levels and to ameliorate GABA deficits in patients with mood disorders. The preponderance of available evidence suggests that glutamatergic and GABAergic modulation may be an important property of available antidepressant and mood-stabilizing agents. Future research will be needed to develop and evaluate new agents with specific glutamate and GABA receptor targets in the treatment of mood disorders.
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                Author and article information

                Journal
                J Biomed Sci
                Journal of Biomedical Science
                BioMed Central
                1021-7770
                1423-0127
                2012
                24 February 2012
                : 19
                : 1
                : 25
                Affiliations
                [1 ]Department of Zoology, CMS College Kottayam, Kerala-686 001, India
                [2 ]Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India
                Article
                1423-0127-19-25
                10.1186/1423-0127-19-25
                3306740
                22364254
                3084dd67-b29e-4805-aece-a71503d1f5f8
                Copyright ©2012 Mathew et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 August 2011
                : 24 February 2012
                Categories
                Research

                Molecular medicine
                carbamazepine,pilocarpine,bacoside-a,epilepsy,bacopa monnieri
                Molecular medicine
                carbamazepine, pilocarpine, bacoside-a, epilepsy, bacopa monnieri

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