Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)mode...Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.展开更多
Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which l...Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which leads to intellectual disability and social impairment. γ-aminobutyric acid （GABA） is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms： the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.展开更多
Aim To investigate the mechanisms underlying depressive-like behavior induced by chronic cerebral is- chemia in rats. Methods In the present study, a chronic cerebral hypoperfusion model was established by perma- 2VO...Aim To investigate the mechanisms underlying depressive-like behavior induced by chronic cerebral is- chemia in rats. Methods In the present study, a chronic cerebral hypoperfusion model was established by perma- 2VO） in rats. Two weeks after 2VO, GAB- nent bilateral common carotid arteries occlusion （two-vessel occlusion, AB receptor agonist baclofen （25 mg · kg^-1 . d^-1 i p ） was administrated for 21 days. The FST was performed to evaluate depressive-like behavior in which the immobility time was recorded. In addition, the expression of brain derived neurotrophic factor （BDNF） in hippocampal CA1 was measured by Western blot. Results The immobility time of 2VO group was significantly prolonged and the expression of BDNF was decreased by 28.95% compared with sham group. After activation of GABAB receptors by baclofen, the immobility time was significantly reduced and the expression of BDNF was increased by 47.91% compared with 2VO group. Conclusion 2VO induced ob- vious depressive-like behavior in rats. Activation of GABAB receptors alleviates the depressive-like behavior in- duced by chronic cerebral ischemia via upredulation of BDNF in hippocampal CA1 in rats.展开更多
γ-amidobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and mediates fast synaptic inhibition through GABAA and GABAC
基金supported by the National Natural Science Foundation of China(No.82471229)Science and Technology Collaborative Innovation Fund of Fujian Province(No.2021Y9172)the Natural Science Foundation of Fujian Province,China(No.2023J01169)。
文摘Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.
文摘Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which leads to intellectual disability and social impairment. γ-aminobutyric acid （GABA） is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms： the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.
文摘Aim To investigate the mechanisms underlying depressive-like behavior induced by chronic cerebral is- chemia in rats. Methods In the present study, a chronic cerebral hypoperfusion model was established by perma- 2VO） in rats. Two weeks after 2VO, GAB- nent bilateral common carotid arteries occlusion （two-vessel occlusion, AB receptor agonist baclofen （25 mg · kg^-1 . d^-1 i p ） was administrated for 21 days. The FST was performed to evaluate depressive-like behavior in which the immobility time was recorded. In addition, the expression of brain derived neurotrophic factor （BDNF） in hippocampal CA1 was measured by Western blot. Results The immobility time of 2VO group was significantly prolonged and the expression of BDNF was decreased by 28.95% compared with sham group. After activation of GABAB receptors by baclofen, the immobility time was significantly reduced and the expression of BDNF was increased by 47.91% compared with 2VO group. Conclusion 2VO induced ob- vious depressive-like behavior in rats. Activation of GABAB receptors alleviates the depressive-like behavior in- duced by chronic cerebral ischemia via upredulation of BDNF in hippocampal CA1 in rats.
文摘γ-amidobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and mediates fast synaptic inhibition through GABAA and GABAC
