Differential regulation of GSK-3β in spinal dorsal horn and in hippocampus mediated by interleukin-1beta contributes to pain hypersensitivity and memory deficits following peripheral nerve injury
| Autor: | Li-Jun Zhou, Xiao Wei, Ying-Tong Meng, Zhen-Jia Lin, Ya-Nan Xu, Chun-Lin Mai, Yong-Yong Li, Zhi Tan, Xian-Guo Liu, Wen-Shan Gui, Jun Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Indoles Time Factors Hippocampus spared nerve injury Maleimides Rats Sprague-Dawley 0302 clinical medicine Peripheral Nerve Injuries Medicine Urea Enzyme Inhibitors beta Catenin Pain Measurement interleukin-1beta integumentary system biology Interleukin-1beta brain-derived neurotrophic factor Hyperalgesia Peripheral nerve injury Neuropathic pain Molecular Medicine Corrigendum Research Article Dorsum Glycogen synthase kinase-3beta Spinal Cord Dorsal Horn Nerve Tissue Proteins 03 medical and health sciences Cellular and Molecular Neuroscience Animals Glycogen synthase Brain-derived neurotrophic factor neuropathic pain Memory Disorders Glycogen Synthase Kinase 3 beta business.industry memory deficits Differential regulation Rats Disease Models Animal Thiazoles 030104 developmental biology Anesthesiology and Pain Medicine Gene Expression Regulation nervous system biology.protein business human activities Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Molecular Pain |
| ISSN: | 1744-8069 |
| Popis: | Accumulating evidence shows that inhibition of glycogen synthase kinase-3beta (GSK-3β) ameliorates cognitive impairments caused by a diverse array of diseases. Our previous work showed that spared nerve injury (SNI) that induces neuropathic pain causes short-term memory deficits. Here, we reported that GSK-3β activity was enhanced in hippocampus and reduced in spinal dorsal horn following SNI, and the changes persisted for at least 45 days. Repetitive applications of selective GSK-3β inhibitors (SB216763, 5 mg/kg, intraperitoneally, three times or AR-A014418, 400 ng/kg, intrathecally, seven times) prevented short-term memory deficits but did not affect neuropathic pain induced by SNI. Surprisingly, we found that the repetitive SB216763 or AR-A014418 induced a persistent pain hypersensitivity in sham animals. Mechanistically, both β-catenin and brain-derived neurotrophic factor (BDNF) were upregulated in spinal dorsal horn but downregulated in hippocampus following SNI. Injections of SB216763 prevented the BDNF downregulation in hippocampus but enhanced its upregulation in spinal dorsal horn in SNI rats. In sham rats, SB216763 upregulated both β-catenin and BDNF in spinal dorsal horn but affect neither of them in hippocampus. Finally, intravenous injection of interleukin-1beta that induces pain hypersensitivity and memory deficits mimicked the SNI-induced the differential regulation of GSK-3β/β-catenin/BDNF in spinal dorsal horn and in hippocampus. Accordingly, the prolonged opposite changes of GSK-3β activity in hippocampus and in spinal dorsal horn induced by SNI may contribute to memory deficits and neuropathic pain by differential regulation of BDNF in the two regions. GSK-3β inhibitors that treat cognitive disorders may result in a long-lasting pain hypersensitivity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|