Purinergic receptors have been reported to be involved in brain disorders.In this study,we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus(T2 DM).T2 DM rats e...Purinergic receptors have been reported to be involved in brain disorders.In this study,we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus(T2 DM).T2 DM rats exhibited a worse performance in the T-maze and Morris water maze(MWM) than controls.Microglia positive for P2 X purinoceptor 4(P2 X4 R) in the hippocampus were reduced and activated microglia were increased in T2 DM rats.Long Amplicon PCR(LA-PCR) showed that DNA amplification of the p2 x4 r gene in the hippocampus was lower in T2 DM rats.Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2 DM rats in the MWM.Most importantly,P2 X4 R overexpression suppressed the activated microglia and rescued the memory impairment of T2 DM rats.Overall,T2 DM led to excessive activation of microglia in the hippocampus,partly through the DNA damagemediated downregulation of P2 X4 Rs,thus contributing to memory impairment.展开更多
Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) was reported to improve visceral hypersensitivity in rats, Colorectal distension was utilized to generate a rat model of chronic visceral hypersensitivity ...Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) was reported to improve visceral hypersensitivity in rats, Colorectal distension was utilized to generate a rat model of chronic visceral hypersensitivity in irritable bowel syndrome, Results showed that abdominal withdrawal reflex scores noticeably increased after model establishment. Simultaneously, P2X4 receptor immunore- activity significantly increased in the colon and spinal cord. Electroacupuncture and pinaverium bromide therapy both markedly decreased abdominal withdrawal reflex scores in rats with visceral hypersensitivity, and significantly decreased P2X4 receptor immunoreactivity in the colon and spinal cord. These data suggest that electroacupuncture treatment can improve visceral hypersensitivity in rats with irritable bowel syndrome by diminishing P2X4 receptor immunoreactivity in the colon and spinal cord,展开更多
Interleukin-1α and interleukin-1β aggravate neuronal injury by mediating the inf1αmmatory reaction following ischemic/hypoxic brain injury. It remains unclear whether interleukin-1α and interleukin-1β are release...Interleukin-1α and interleukin-1β aggravate neuronal injury by mediating the inf1αmmatory reaction following ischemic/hypoxic brain injury. It remains unclear whether interleukin-1α and interleukin-1β are released by microglia or astrocytes. This study prepared hippocampal slices that were subsequently subjected to oxygen and glucose deprivation. Hematoxylin-eosin staining verified that neurons exhibited hypoxic changes. Results of enzyme-linked immunosorbent assay found that interleukin-1α and interleukin-1β participated in this hypoxic process. Moreover, when hypoxic injury occurred in the hippocampus, the release of interleukin-1α and interleukin-1β was mediated by the P2X4 receptor and P2X7 receptor. Immunofluorescence staining revealed that during ischemia/hypoxia, the P2X4 receptor, P2X7 receptor, interleukin-1α and interleukin-1β expression was detectable in rat hippocampal microglia, but only P2X4 receptor and P2X7 receptor expression was detected in astrocytes. Results suggested that the P2X4 receptor and P2X7 receptor, respectively, mediated interleukin-1α and interleukin-1β released by microglia, resulting in hippocampal ischemic/hypoxic injury. Astrocytes were activated, but did not synthesize or release interleukin-1α and interleukin-1β.展开更多
基金supported by grants from the National Natural Science Foundation of China (31730040,81801115, and 81920108016)the China Postdoctoral Science Foundation (2018M642304)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China。
文摘Purinergic receptors have been reported to be involved in brain disorders.In this study,we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus(T2 DM).T2 DM rats exhibited a worse performance in the T-maze and Morris water maze(MWM) than controls.Microglia positive for P2 X purinoceptor 4(P2 X4 R) in the hippocampus were reduced and activated microglia were increased in T2 DM rats.Long Amplicon PCR(LA-PCR) showed that DNA amplification of the p2 x4 r gene in the hippocampus was lower in T2 DM rats.Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2 DM rats in the MWM.Most importantly,P2 X4 R overexpression suppressed the activated microglia and rescued the memory impairment of T2 DM rats.Overall,T2 DM led to excessive activation of microglia in the hippocampus,partly through the DNA damagemediated downregulation of P2 X4 Rs,thus contributing to memory impairment.
基金supported by the National Natural Science Foundation of China,No.30973783the Open Research Fund of Zhejiang First-foremost Key Subject--Acupuncture & Moxibustion,No.ZTK2010A01the scientific research grants of Shanghai Health Bureau,No.2009209
文摘Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) was reported to improve visceral hypersensitivity in rats, Colorectal distension was utilized to generate a rat model of chronic visceral hypersensitivity in irritable bowel syndrome, Results showed that abdominal withdrawal reflex scores noticeably increased after model establishment. Simultaneously, P2X4 receptor immunore- activity significantly increased in the colon and spinal cord. Electroacupuncture and pinaverium bromide therapy both markedly decreased abdominal withdrawal reflex scores in rats with visceral hypersensitivity, and significantly decreased P2X4 receptor immunoreactivity in the colon and spinal cord. These data suggest that electroacupuncture treatment can improve visceral hypersensitivity in rats with irritable bowel syndrome by diminishing P2X4 receptor immunoreactivity in the colon and spinal cord,
基金supported by the Natural Science Foundation of Guangdong Province,No.S2011010004096
文摘Interleukin-1α and interleukin-1β aggravate neuronal injury by mediating the inf1αmmatory reaction following ischemic/hypoxic brain injury. It remains unclear whether interleukin-1α and interleukin-1β are released by microglia or astrocytes. This study prepared hippocampal slices that were subsequently subjected to oxygen and glucose deprivation. Hematoxylin-eosin staining verified that neurons exhibited hypoxic changes. Results of enzyme-linked immunosorbent assay found that interleukin-1α and interleukin-1β participated in this hypoxic process. Moreover, when hypoxic injury occurred in the hippocampus, the release of interleukin-1α and interleukin-1β was mediated by the P2X4 receptor and P2X7 receptor. Immunofluorescence staining revealed that during ischemia/hypoxia, the P2X4 receptor, P2X7 receptor, interleukin-1α and interleukin-1β expression was detectable in rat hippocampal microglia, but only P2X4 receptor and P2X7 receptor expression was detected in astrocytes. Results suggested that the P2X4 receptor and P2X7 receptor, respectively, mediated interleukin-1α and interleukin-1β released by microglia, resulting in hippocampal ischemic/hypoxic injury. Astrocytes were activated, but did not synthesize or release interleukin-1α and interleukin-1β.