The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity, and neuroprotection. In a recent study, we showed that Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat shock factor 1 (HSF1). Following single injection of Oxotremorine-M (0.4 mg/kg) all Hsps examined were significantly increased in at least one of the time points studied (24, 48, and 72 hr). Treatment with Oxotremorine-M significantly increased the level of phosphorylated HSF1 in all time points studied, without change of protein levels. Similar pattern of Hsps changes was obtained following chronic Oxotremorine-M treatment (0.2 mg/kg) for 5 days. Surprisingly, following chronic treatment for 10 days no changes were observed in Hsps. The muscarinic acetylcholine receptor antagonist scopolamine (1 mg/kg) was able to completely block Oxotremorine-M effects on Hsps. In conclusion, considering the function of Hsps in protecting neuronal cells from deleterious proteotoxic stress, for example, protein mis-folding and aggregation, the results obtained indicate that muscarinic acetylcholine receptor activation may have implications in potential treatment of neurodegenerative disorders linked to protein aggregation, such as Alzheimer disease.

Frinchi, M., Scaduto, P., Cappello, F., Belluardo, N., Mudò, G. (2018). Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus. JOURNAL OF CELLULAR PHYSIOLOGY, 233(8), 6107-6116 [10.1002/jcp.26454].

Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Frinchi, Monica;SCADUTO, Pietro;Cappello, Francesco;Belluardo, Natale;Mudò, Giuseppa
2018-01-01

Abstract

The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity, and neuroprotection. In a recent study, we showed that Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat shock factor 1 (HSF1). Following single injection of Oxotremorine-M (0.4 mg/kg) all Hsps examined were significantly increased in at least one of the time points studied (24, 48, and 72 hr). Treatment with Oxotremorine-M significantly increased the level of phosphorylated HSF1 in all time points studied, without change of protein levels. Similar pattern of Hsps changes was obtained following chronic Oxotremorine-M treatment (0.2 mg/kg) for 5 days. Surprisingly, following chronic treatment for 10 days no changes were observed in Hsps. The muscarinic acetylcholine receptor antagonist scopolamine (1 mg/kg) was able to completely block Oxotremorine-M effects on Hsps. In conclusion, considering the function of Hsps in protecting neuronal cells from deleterious proteotoxic stress, for example, protein mis-folding and aggregation, the results obtained indicate that muscarinic acetylcholine receptor activation may have implications in potential treatment of neurodegenerative disorders linked to protein aggregation, such as Alzheimer disease.
2018
Frinchi, M., Scaduto, P., Cappello, F., Belluardo, N., Mudò, G. (2018). Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus. JOURNAL OF CELLULAR PHYSIOLOGY, 233(8), 6107-6116 [10.1002/jcp.26454].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/295439
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