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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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Decreased GABA Receptor in the Cerebral Cortex of Epileptic Rats: Effect of Bacopa Monnieri and Bacoside-A

Jobin Mathew et al. J Biomed Sci.

Abstract

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, GABAA and GABAB 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 Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 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.

Figures

Figure 1
Figure 1
Representative graph showing Real-Time amplification of GABA Aα1 receptor subunit mRNA from the Control and experimental rats. The ΔΔCT method of relative quantification was used to determine the fold change in expression. Values are mean ± S.D of 4-6 separate experiments. C- Control, E- Epileptic, E+B- Epileptic + Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats. ***p < 0.001 when compared to control, @@@p < 0.001 when compared to epileptic group.
Figure 2
Figure 2
Representative graph showing Real-Time amplification of GABAAα5 receptor subunit mRNA from the Control and experimental rats. The ΔΔCT method of relative quantification was used to determine the fold change in expression. Values are mean ± S.D of 4-6 separate experiments. C- Control, E- Epileptic, E+B- Epileptic + Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats. ***p < 0.001 when compared to control, @@@p < 0.001 when compared to epileptic group.
Figure 3
Figure 3
Representative graph showing Real-Time amplification of GABA Aγ5 receptor subunit mRNA from the Control and experimental rats. The ΔΔCT method of relative quantification was used to determine the fold change in expression. Values are mean ± S.D of 4-6 separate experiments. C- Control, E- Epileptic, E+B- Epileptic + Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats. ***p < 0.001 when compared to control, @@@p < 0.001 when compared to epileptic group.
Figure 4
Figure 4
Representative graph showing Real-Time amplification of GABA Aδ5 receptor subunit mRNA from the Control and experimental rats. The ΔΔCT method of relative quantification was used to determine the fold change in expression. Values are mean ± S.D of 4-6 separate experiments. C- Control, E- Epileptic, E+B- Epileptic + Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats. ***p < 0.001 when compared to control, @@@p < 0.001 when compared to epileptic group.
Figure 5
Figure 5
Representative graph showing Real-Time amplification of GABAB receptor mRNA from the Control and experimental rats. The ΔΔCT method of relative quantification was used to determine the fold change in expression. Values are mean ± S.D of 4-6 separate experiments. C- Control, E- Epileptic, E+B- Epileptic + Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats. ***p < 0.001 when compared to control, @@@p < 0.001 when compared to epileptic group.
Figure 6
Figure 6
Representative graph showing Real-Time amplification of GAD mRNA from the Control and experimental rats. The ΔΔCT method of relative quantification was used to determine the fold change in expression. Values are mean ± S.D of 4-6 separate experiments. C- Control, E- Epileptic, E+B- Epileptic+ Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats. ***p < 0.001 when compared to control, @@@p < 0.001 when compared to epileptic group.
Figure 7
Figure 7
Representative graph showing Real-Time amplification of CREB mRNA from the Control and experimental rats. The ΔΔCT method of relative quantification was used to determine the fold change in expression. Values are mean ± S.D of 4-6 separate experiments. C- Control, E- Epileptic, E+B- Epileptic+ Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats. ***p < 0.001 when compared to control, @@p < 0.01, @p < 0.05 when compared to epileptic group.
Figure 8
Figure 8
Representative graph showing radial arm maze performance of control and experimental rats epileptic rats required more daily trials to achieve three, four, and five consecutive criterion performances. Criterion performance was defined as consumption of the bait in the four baited arms of the radial maze during no more than five entries. There was no significant difference in the average number of trials required by kindled and control rats to achieve the initial criterion performance. C- Control, E- Epileptic, E+B- Epileptic + Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats.
Figure 9
Figure 9
Representative graph showing Y maze performance of control and experimental rats. Epileptic rats showed less exploratory behavior compared to control. C- Control, E- Epileptic, E+B- Epileptic + Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats. **p < 0.01 when compared to control, @@p < 0.01 and @p < 0.05 when compared to epileptic group.
Figure 10
Figure 10
GABAAα1 receptor subunit antibody staining in the cerebral cortex of Control. and experimental rats. C- Control, E- Epileptic, E+B- Epileptic + Bacopa monnieri, E+D- Epileptic + Bacoside-A, E+C- Epileptic + carbamazepine treated rats. Pixel intensity of experimental rats were C-103465 ± 3043, E- 76456 ± 1593**, E+B-95835@@ ± 2935, E+D-90564 ± 2553@@, E+C-87593 ± 1093@@. () Indicating the GABAAα1 receptor subunit. **p < 0.01 when compared to control, @@p < 0.01 when compared to epileptic group.

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