title: Dexmedetomidine protects against learning and memory impairments caused by electroconvulsive shock in depressed rats: Involvement of the NMDA receptor subunit 2B (NR2B)-ERK signaling pathway.
abstract: Cognitive impairment is a common adverse effect of electroconvulsive therapy (ECT) during treatment for severe depression. Dexmedetomidine (DEX), a sedative-anesthetic drug, is used to treat post-ECT agitation. However, it is not known if DEX can protect against ECT-induced cognitive impairments. To address this, we used chronic unpredictable mild stress (CUMS) to establish a model of depression for ECT treatment. Our Morris water maze and sucrose preference test results suggest that DEX alleviates ECT-induced learning and memory impairments without altering the antidepressant efficacy of ECT. To further investigate the underlying mechanisms of DEX, hippocampal expression of NR2B, p-ERK/ERK, p-CREB/CREB, and BDNF were quantified by western blotting. These results show that DEX suppresses over-activation of NR2B and enhances phosphorylation of ERK1/2 in the hippocampus of ECT-treated depressed rats. Furthermore, DEX had no significant effect on ECT-induced increases in p-CREB and BDNF. Overall, our findings suggest that DEX ameliorates ECT-induced learning and memory impairments in depressed rats via the NR2B-ERK signaling cascade. Moreover, CREB/BDNF seems not appear to participate in the cognitive protective mechanisms of DEX during ECT treatment.
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Fu-Zhi
authors.initials: FZ
authors.lastname: Zhuang
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Shou-Jun
authors.initials: SJ
authors.lastname: Qin
authors.affiliation: Department of Anaesthesiology, The Affiliated Hospital of Xuzhou Medical University, Key Laboratory for Anesthesiology of Jiangsu Province, Xuzhou 221004, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Geriatric Psychiatry, The East People's Hospital of Xuzhou, Xuzhou 221004, Jiangsu, China.
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Texas A&M University'16, College Station 77841, TX, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Villarreal
authors.affiliation: Texas A&M University'16, College Station 77841, TX, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: Benefield
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Gu
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. Electronic address: tengfeimtf@gmail.com.
authors.forename: Teng-Fei
authors.initials: TF
authors.lastname: Ma
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000628:therapy*; D020927:Dexmedetomidine / Q000494:pharmacology*; D004597:Electroshock / Q000009:adverse effects*; D006624:Hippocampus / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D006993:Hypnotics and Sedatives; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D020927:Dexmedetomidine
keywords: Dexmedetomidine; ECT; Neuroprotection; cognition; depression