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https://link.springer.com/article/10.1007/s12035-022-02940-1

Published: 04 July 2022
Muscarinic Acetylcholine Receptors-Mediated Activation of PKC Restores the Hippocampal Immediate Early Gene Expression and CREB Phosphorylation in Scopolamine-Induced Amnesic Mice
Bhabotosh Barman, Akanksha Kushwaha & Mahendra Kumar Thakur
Molecular Neurobiology (2022)Cite this article

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Abstract
Amnesia is the inability to store new information and recall old memories. After the postulation of cholinergic hypothesis of geriatric memory dysfunction, the cholinergic signaling became a popular target to understand the underlying molecular mechanism of amnesia and its recovery. Scopolamine is a non-selective cholinergic receptor antagonist and induces amnesia through downregulation of synaptic plasticity genes including immediate early genes (IEGs). Scopolamine-induced amnesic mouse model is widely used to study the memory impairment that mimics the pathophysiology of aging, neurodegenerative, and neuropsychiatric disorders. However, a detailed understanding of cholinergic signaling-mediated regulation of plasticity-related gene expression remains elusive. Therefore, we have investigated the role of muscarinic acetylcholine receptors (mAChRs) and their downstream mediator protein kinase C (PKC) in the regulation of IEGs expression in amnesic mice hippocampus. Pilocarpine, a mAChRs agonist, was used to activate the cholinergic signaling in scopolamine-induced amnesia. Further, a PKC activator bryostatin 1 was used to understand the sole involvement of PKC as a downstream mediator of mAChRs-mediated signaling. Pilocarpine treatment significantly restored the scopolamine-induced impaired recognition memory and downregulated hippocampal IEGs expression and phosphorylation of ERK1/2 (extracellular signal-regulated kinase 1/2) and CREB (cAMP response element-binding protein). On the other hand, the bryostatin 1-mediated activation of PKC in scopolamine-induced amnesia selectively restored the hippocampal IEGs expression, recognition memory, and phosphorylation of ERK1/2 and CREB. Taken together, our findings suggest that mAChRs and their downstream mediator PKC regulate the hippocampal IEGs expression and ERK1/2-mediated CREB phosphorylation in scopolamine-induced amnesic mice.