Modulation of GSK-3β/β-Catenin Signaling Contributes to Learning and Memory Impairment in a Rat Model of Depression
| Autor: | Jian-Ping Zhang, Jiaojie Hui, Jing-Jing Wu, Xingliang Zhou, Jian Zou, Mengjia Pu, Guo-Feng Shi, Guangjun Xi, Xuqiang Mao, Dongmei Jiang, Liang Dong |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Indoles Morris water navigation task Hippocampus Hippocampal formation Regular Research Articles Maleimides Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Corticosterone Medicine glycogen synthase kinase-3 beta Pharmacology (medical) Nootropic Agents beta Catenin Learning Disabilities Gene Transfer Techniques Uncertainty Psychiatry and Mental health depression Intercellular Signaling Peptides and Proteins learning and memory Signal transduction Glucocorticoid Signal Transduction medicine.drug 03 medical and health sciences Animals Memory impairment Cognitive Dysfunction Effects of sleep deprivation on cognitive performance Maze Learning Pharmacology Depressive Disorder Memory Disorders Glycogen Synthase Kinase 3 beta business.industry β-catenin Disease Models Animal 030104 developmental biology chemistry chronic unpredictable mild stress business Neuroscience Stress Psychological 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Neuropsychopharmacology |
| ISSN: | 1469-5111 1461-1457 |
| DOI: | 10.1093/ijnp/pyy040 |
| Popis: | Background It is widely accepted that cognitive processes, such as learning and memory, are affected in depression, but the molecular mechanisms underlying the interactions of these 2 disorders are not clearly understood. Recently, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling was shown to play an important role in the regulation of learning and memory. Methods The present study used a rat model of depression, chronic unpredictable stress, to determine whether hippocampal GSK-3β/β-catenin signaling was involved in learning and memory alterations. Results Our results demonstrated that chronic unpredictable stress had a dramatic influence on spatial cognitive performance in the Morris water maze task and reduced the phosphorylation of Ser9 of GSK-3β as well as the total and nuclear levels of β-catenin in the hippocampus. Inhibition of GSK3β by SB216763 significantly ameliorated the cognitive deficits induced by chronic unpredictable stress, while overexpression of GSK3β by AAV-mediated gene transfer significantly decreased cognitive performance in adult rats. In addition, chronic unpredictable stress exposure increased the expression of the canonical Wnt antagonist Dkk-1. Furthermore, chronic administration of corticosterone significantly increased Dkk-1 expression, decreased the phosphorylation of Ser9 of GSK-3β, and resulted in the impairment of hippocampal learning and memory. Conclusions Our results indicate that impairment of learning and memory in response to chronic unpredictable stress may be attributed to the dysfunction of GSK-3β/β-catenin signaling mediated by increased glucocorticoid signaling via Dkk-1. |
| Databáze: | OpenAIRE |
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