Hippocampal Proteomic Analysis in Male Mice Following Aggressive Behavior Induced by Long-Term Administration of Perampanel.

Autor:	Yang W; Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China.; Department of Emergency, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, PR China., Ma L; Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China., Hai DM; Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China., Liu N; Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China., Yang JM; Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China., Lan XB; Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China., Du J; Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China., Yang LS; Department of Emergency, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, PR China., Sun T; Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China.; Ningxia Key Laboratory of Cerebrocranial Disease, The Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China., Yu JQ; Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China.; Ningxia Hui Medicine Modern Engineering Research Center and Collaborative Innovation Center, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China.
Jazyk:	angličtina
Zdroj:	ACS omega [ACS Omega] 2022 Jun 01; Vol. 7 (23), pp. 19388-19400. Date of Electronic Publication: 2022 Jun 01 (Print Publication: 2022).
DOI:	10.1021/acsomega.2c01008
Abstrakt:	Antiepileptic drugs have been shown to be associated with inducing or exacerbating adverse psychotropic reaction, including aggressive behavior. Perampanel, the first pharmacological compound approved by the FDA in 2012, is an effective antiepileptic drug for intractable epilepsy but induces severe aggression. So far, the underlying molecular mechanisms of aggression induced by perampanel remain incompletely understood. In the present study, a model of aggressive behavior based on the clinical use of perampanel was established and resident-intruder test and open field test were performed. Changes in hippocampal protein profiles were detected by tandem mass tag (TMT) proteomics. The behavioral results indicated that long-term use of perampanel increased the aggressive behavior of C57BL/6J mice. Proteomic analysis revealed that 93 proteins were significantly altered in the hippocampus of the perampanel-treated group (corrected p < 0.05), which were divided into multiple functional groups, mainly related to synaptic function, synaptogenesis, postsynaptic density protein, neurite outgrowth, AMPA-type glutamate receptor immobilization, and others. Bioinformatic analysis showed that differentially expressed proteins were involved in synaptic plasticity and the Ras signaling pathway. Furthermore, validation results by western blot demonstrated that glutamate receptor 1 (GluA1) and phosphorylation of mitogen-activated protein kinase (ERK1/2) were notably up-regulated, and synaptophysin ( Syn ) and postsynaptic density 95 (PSD95) were down-regulated in perampanel-treated mice. Therefore, our results provide valuable insight into the molecular mechanisms of aggressive behavior induced by perampanel, as well as potential options for safety treatment of perampanel in the future. Competing Interests: The authors declare no competing financial interest. (© 2022 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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