Oxidative stress induced NMDA receptor alteration leads to spatial memory deficits in temporal lobe epilepsy

Ameliorative effects of Withania somnifera and Withanolide A

Smijin Soman, Korah Pushpamangalam Kuruvilla, S. Jayanarayanan, Jobin Mathew, C. S. Paulose

Research output: Contribution to journalArticle

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Abstract

In the present study we investigate the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring spatial memory deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. We demonstrate significant cellular loss in hippocampus of epileptic rats, visualized through decreased TOPRO stained neurons. Impaired spatial memory was observed in epileptic rats after Radial arm maze test. Treatment with WS and WA has resulted in increased number of TOPRO stained neurons. Enhanced performance of epileptic rats treated with WS and WA was observed in Radial arm maze test. The antioxidant activity of WS and WA was studied using superoxide dismutase (SOD) and Catalase (CAT) assays in the hippocampus of experimental rats. The SOD activity and CAT activity decreased significantly in epileptic group, treatment with WS and WA significantly reversed the enzymatic activities to near control. Real time gene expression studies of SOD and GPx showed significant up-regulation in epileptic group compared to control. Treatment with WS and WA showed significant reversal to near control. Lipid peroxidation quantified using TBARS assay, significantly increased in epileptic rats. Treatment withWSandWAshowed significant reversal to near control. NMDA receptor expression decreased in epileptic rats. The treatment with WS and WA resulted in physiological expression of NMDA receptors. This data suggests that oxidative stress effects membrane constitution resulting in decreased NMDA receptor density leading to impaired spatial memory. Treatment with WS and WA has ameliorated spatial memory deficits by enhancing antioxidant system and restoring altered NMDA receptor density.

Original languageEnglish (US)
Pages (from-to)1915-1927
Number of pages13
JournalNeurochemical Research
Volume37
Issue number9
DOIs
StatePublished - Sep 1 2012

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Withania
Oxidative stress
Temporal Lobe Epilepsy
Memory Disorders
N-Methyl-D-Aspartate Receptors
Oxidative Stress
Data storage equipment
Rats
Superoxide Dismutase
Catalase
Neurons
Assays
Hippocampus
Antioxidants
Spatial Memory
3-rhamnopyranosyl(1-4)-glucopyranosyl-12-diacetoxy-20-hydroxywitha-5,24-dienolide
Constitution and Bylaws
Gene expression
Synaptic Transmission
Lipid Peroxidation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Oxidative stress induced NMDA receptor alteration leads to spatial memory deficits in temporal lobe epilepsy : Ameliorative effects of Withania somnifera and Withanolide A. / Soman, Smijin; Pushpamangalam Kuruvilla, Korah; Jayanarayanan, S.; Mathew, Jobin; Paulose, C. S.

In: Neurochemical Research, Vol. 37, No. 9, 01.09.2012, p. 1915-1927.

Research output: Contribution to journalArticle

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