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Upregulation of miR-19b-3p exacerbates chronic stress-induced changes in synaptic plasticity and cognition by targeting Drebrin.
Chen, Jingli; Liu, Chang; Xu, Mu; Zhu, Jiaxi; Xia, Zhongyuan.
Affiliation
  • Chen J; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China; Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China.
  • Liu C; Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China; Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Sci
  • Xu M; Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China; Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Sci
  • Zhu J; Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China; Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Sci
  • Xia Z; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China. Electronic address: xiazhongyuan2005@aliyun.com.
Neuropharmacology ; 207: 108951, 2022 04 01.
Article in En | MEDLINE | ID: mdl-35041806
Chronic stress is associated with impairment of synapse plasticity in hippocampus and cognitive dysfunction in rodent and human. Notably, corticosterone (CORT) is believed to take responsibility for dendritic atrophy and reduction of spine number induced by chronic stress in hippocampus. But little is known about the molecular mechanisms underlying CORT induced abnormal synapse plasticity and cognitive dysfunction. Drebrin is an F-actin binding protein that modulates memory formation and maintenance by controlling the genesis and morphology of dendritic spines. In addition, miRNAs have been reported to participate in the negative regulation of protein-coding genes. In this study, five miRNAs capable of targeting Drebrin were selected by searching miRNA databases. One of these miRNAs, miR-19b-3p, was found to be upregulated in the hippocampal neurons of mice with chronic restraint stress (CRS). Luciferase reporter assay and Fluorescence in situ hybridization (FISH) were employed to identify the interaction between miR-19b-3p and Drebrin. In addition, silencing miR-19b-3p expression in vivo using an antagomir or in vitro using an inhibitor increased Drebrin expression, ameliorated the abnormal dendritic structure and upregulated the spine density in hippocampal CA1 pyramidal neurons of CRS mice and primary hippocampal neurons cultured under CORT stimulation, respectively. Electrophysiological analysis revealed that inhibition of miR-19b-3p rescued the limited synaptic transmission and synaptic plasticity in hippocampal neurons. Moreover, blocking miR-19b-3p drastically protected against cognitive deficits in CRS mice. These in vivo and in vitro findings indicate that the upregulation of miR-19b-3p exacerbates CRS-induced abnormal synaptic plasticity and cognitive impairment by targeting Drebrin.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neuropeptides / MicroRNAs / Cognitive Dysfunction / Neuronal Plasticity Type of study: Etiology_studies / Prognostic_studies Limits: Animals Language: En Journal: Neuropharmacology Year: 2022 Document type: Article Affiliation country: China Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neuropeptides / MicroRNAs / Cognitive Dysfunction / Neuronal Plasticity Type of study: Etiology_studies / Prognostic_studies Limits: Animals Language: En Journal: Neuropharmacology Year: 2022 Document type: Article Affiliation country: China Country of publication: Reino Unido