Behavioral Deficit and Decreased GABA Receptor Functional Regulation in the Hippocampus of Epileptic Rats: Effect of Bacopa monnieri

Abstract

In the present study, alterations of the General GABA and GABA(A) receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B(max) (P < 0.001) compared to control. Real Time PCR amplification of GABA(A) receptor sub-units such as GABA(Aά₁), GABA(Aά₅) GABA(Aδ), and GAD were down regulated (P < 0.001) in the hippocampus of the epileptic rats compared to control. GABA(Aγ) subunit was up regulated. Epileptic rats have deficit in the radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.

A bacosides containing Bacopa monnieri extract alleviates allodynia and hyperalgesia in the chronic constriction injury model of neuropathic pain in rats

“…Although, the mechanism through which Bacopa monnieri ameliorates allodynia and hyperalgesia is still unknown; nonetheless, in view of its myriad pharmacological profile it can be speculated that multiple mechanisms might be involved as Bacopa monnieri possesses anti-nociceptive activity [30] mediated through opioidergic mechanisms [88], enhances the morphine anti-nociceptive effects [66], increases synaptic plasticity [97], up-regulates vesicular glutamate transporter type 2 (VGLUT2) [98] and decreases the immunodensity of glutamate/ N -methyl-D- aspartate receptor subtype 1 (NMDAR1) [99]. What is more, Bacopa monnieri increases GABA, GABA A receptor subunit, GABA A receptor binding and up-regulation of GAD gene [11]. Additionally, Bacopa monnieri decreases the release of TNF-α and IL-6 [22] and inhibits the activities of COX-2, LOX-5 and LOX-15 [21].…”

Attenuation of 1-(m-Chlorophenyl)-Biguanide Induced Hippocampus-Dependent Memory Impairment by a Standardised Extract of Bacopa monniera (BESEB CDRI-08)

“…A subsequent study has found that bacopa provides protection from phenytoin-induced cognitive impairments [8]. It has been postulated that its anti-epileptic effect could be mediated through glutamate, NMDA R1 [9] and GABA receptor [10], yet another study suggested that BESEB CDRI-08 reduced hypobaric hypoxia induced spatial memory impairment [11]. Furthermore, the efficacy of a bacopa extract in learning and memory have been further established by showing the reversal of diazepam [12] and scopolamine-induced amnesia [13,14] and neuroprotective effect against cholinergic degeneration [5].…”

STE20/SPS1-Related Proline/Alanine-Rich Kinase Is Involved in Plasticity of GABA Signaling Function in a Mouse Model of Acquired Epilepsy

“…This, in turn, reduces the threshold of seizure generation and thus contributes to the onset of seizures. Furthermore, the PISE model used in this study also exhibited inverse function of GABA signaling [32]. There is evidence that seizures beget seizures and that GABA signaling plays a central role in this phenomenon [2].…”