Ameliorative effect of curcumin on altered expression of CACNA1A and GABRD in the pathogenesis of FeCl 3 -induced epilep
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ORIGINAL ARTICLE
Ameliorative effect of curcumin on altered expression of CACNA1A and GABRD in the pathogenesis of FeCl3‑induced epilepsy Prince Kumar1 · Deepak Sharma1 Received: 27 January 2020 / Accepted: 17 May 2020 © Springer Nature B.V. 2020
Abstract The pivotal role played by ion-channel dysregulations in the pathogenesis of epilepsy has always garnered much attention. Since mutation of ion–channel proteins CACNA1A and GABRD have been associated with epilepsy, it is important to determine the post-traumatic epilepsy-associated changes in expression levels of these ion channel proteins. Additionally, curcumin is already known for its antiepileptic and neuroprotective potential in FeCl3-induced model of post-traumatic epilepsy. Thus, we investigated FeCl3-induced epilepsy mediated differential expression of CACNA1A and GABRD in the cortical region of the rat brain. Furthermore, we investigated the effect of curcumin on the expression of both proteins. For this, epilepsy was induced by intracortical F eCl3 injection (5 μl of 100 mM). Additionally, curcumin (conc. 1000 ppm; 75 mg/kg of b.wt.; for 14 and 28 days) was administered, mixed with normal food pellets. Results obtained from EEG-MUA and Morris water maze assay demonstrate the progression of epilepsy after FeCl3 injection. Additionally, western blotting and histological studies show the downregulation of CACNA1A and GABRD during epileptogenesis. It was observed that epilepsy-associated decline in learning and memory of animals might be linked with the dysregulation of both proteins. Results also demonstrated that curcumin administration ameliorated epilepsy-associated change in expression of both CACNA1A and GABRD proteins. In conclusion, the neuroprotective effect of curcumin against iron-induced epilepsy might be accompanied by the alleviated upregulation of these channel proteins. Keywords Post-traumatic epilepsy · Curcumin · Ion channels · CACNA1A · GABRD
Introduction Epilepsy is majorly mediated by imbalances of ions concentration inside neurons as well as across their membranes. Notably, ion channels are integral membrane proteins that play a crucial role in neuron excitation and neuron survival. For the excitation of a neuron or conduction of an electrical signal, movement of ions across the membrane is facilitated by various channel proteins. Most of the channels are gated and their opening is controlled either by alterations in membrane potential or binding of a neurotransmitter ligand to the receptor. Hence, any kind of dysregulation in these ion channels can lead to various neurological disorders. For example, mutations in Na+ and Ca2+ channels are shown to be involved in numerous disorder including ataxia and * Deepak Sharma [email protected] 1
Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
epilepsy [1]. Similarly, mutation in C l− channel is also reported to be involved in various neurological disorders including epilepsy [2]. Glutamate-mediated cellular damage
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