Chronic Pain Impairs Memory Formation via Disruption of Neurogenesis Mediated by Mesohippocampal Brain-Derived Neurotrophic Factor Signaling
| Autor: | Ming-Hu Han, Jun-Li Cao, Ling Yuan, Sun-Hui Xia, Song Zhang, Jun-Xia Yang, Di Liu, Peng Wu, Di Wang, Hongxing Zhang, Qi Zhang, Yan-Qiang Li, Hai-Lei Ding, Su-Wan Hu, De-Gao Ge |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Neurogenesis Hippocampal formation Hippocampus Article Mice 03 medical and health sciences 0302 clinical medicine Neurotrophic factors medicine Animals Humans Memory impairment Biological Psychiatry Brain-derived neurotrophic factor Memory Disorders business.industry Brain-Derived Neurotrophic Factor Dentate gyrus Chronic pain medicine.disease 030104 developmental biology Dentate Gyrus Neuropathic pain Chronic Pain business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Biol Psychiatry |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2020.02.013 |
| Popis: | Background Chronic pain patients often complain of their poor memory. The mechanisms underlying chronic pain–related memory impairment remain elusive, and there are few clinical therapeutic strategies available for this condition. Methods In a neuropathic pain model induced by chronic constrictive injury of the sciatic nerve in male mice, we used circuit-specific electrophysiological recording, combined with chemogenetic, molecular, and pharmacologic methods, to examine the circuit and molecular mechanisms underlying chronic pain–related memory impairment. Results Our current results show that chronic neuropathic pain impaired the acquisition of spatial memory and, meanwhile, reduced adult neurogenesis in the dentate gyrus. Experimentally reducing dentate gyrus neurogenesis mimicked this pain-induced effect on spatial memory formation in naive mice. Furthermore, pain-associated impairments of both hippocampal neurogenesis and memory formation were rescued or mimicked by chemogenetic activation or deactivation, respectively, of the ventral tegmental area dopaminergic projection, through which ventral tegmental area–released brain-derived neurotrophic factor was required. Importantly, we found that chronic, but not acute, systematic administration of subanesthetic doses of ketamine, while without relieving pain, ameliorated chronic pain–related impairment of spatial memory formation, potentially by rescuing brain-derived neurotrophic factor–mediated dentate gyrus neurogenesis. Conclusions These findings provide a novel, circuit-based mechanistic link between chronic pain and memory formation deficit, and potential new therapeutic options for chronic pain–related learning deficit and memory impairment. |
| Databáze: | OpenAIRE |
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