M1 muscarinic receptor is a key target of neuroprotection, neuroregeneration and memory recovery by i-Extract from Withania somnifera

Arpita Konar, Richa Gupta, Rajendra K. Shukla, Bryan Maloney, Vinay K. Khanna, Renu Wadhwa, Debomoy K. Lahiri, Mahendra K. Thakur

Research output: Contribution to journalArticle

Abstract

Memory loss is one of the most tragic symptoms of Alzheimer’s disease. Our laboratory has recently demonstrated that ‘i-Extract’ of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate memory processes. The present study elucidates key target(s) of i-Extract via cellular, biochemical, and molecular techniques in a relevant amnesia mouse model and primary hippocampal neuronal cultures. Wild type Swiss albino mice were fed i-Extract, and hippocampal cells from naïve mice were treated with i-Extract, followed by muscarinic antagonist (dicyclomine) and agonist (pilocarpine) treatments. We measured dendritic formation and growth by immunocytochemistry, kallikrein 8 (KLK8) mRNA by reverse transcription polymerase chain reaction (RT-PCR), and levels of KLK8 and microtubule-associated protein 2, c isoform (MAP2c) proteins by western blotting. We performed muscarinic receptor radioligand binding. i-Extract stimulated an increase in dendrite growth markers, KLK8 and MAP2. Scopolamine-mediated reduction was significantly reversed by i-Extract in mouse cerebral cortex and hippocampus. Our study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.

Original languageEnglish (US)
Article number13990
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Withania
Muscarinic M1 Receptors
Kallikreins
Muscarinic Receptors
Scopolamine Hydrobromide
Memory Disorders
Dicyclomine
Muscarinic Agonists
Pilocarpine
Muscarinic Antagonists
Microtubule-Associated Proteins
Amnesia
Growth
Dendrites
Cell Extracts
Neurodegenerative Diseases
Cerebral Cortex
Reverse Transcription
Hippocampus
Alzheimer Disease

ASJC Scopus subject areas

  • General

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M1 muscarinic receptor is a key target of neuroprotection, neuroregeneration and memory recovery by i-Extract from Withania somnifera. / Konar, Arpita; Gupta, Richa; Shukla, Rajendra K.; Maloney, Bryan; Khanna, Vinay K.; Wadhwa, Renu; Lahiri, Debomoy K.; Thakur, Mahendra K.

In: Scientific reports, Vol. 9, No. 1, 13990, 01.12.2019.

Research output: Contribution to journalArticle

Konar, Arpita ; Gupta, Richa ; Shukla, Rajendra K. ; Maloney, Bryan ; Khanna, Vinay K. ; Wadhwa, Renu ; Lahiri, Debomoy K. ; Thakur, Mahendra K. / M1 muscarinic receptor is a key target of neuroprotection, neuroregeneration and memory recovery by i-Extract from Withania somnifera. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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