Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus ner...Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.展开更多
Orexin signaling has been associated with energy expenditure and brown adipose tissue(BAT)function.However,conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis.In this study,we sh...Orexin signaling has been associated with energy expenditure and brown adipose tissue(BAT)function.However,conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis.In this study,we show that a specific orexin receptor type 2(OX2R)agonist[Ala11,D-Leu15]-OxB(OB-Ala)inhibited intrascapular brown adipose tissue(iBAT)thermogenesis by reducing sympathetic output to iBAT.This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself.Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus.Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop.Our study uncovers a novel primary action site of orexin in the regulation of energy balance.展开更多
OBJECTIVE:To investigate the protective effects of Zuogui Wan(左归丸,ZGW)on bone loss induced by ovariectomy(OVX)and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model.METHODS:Fifty Sprague-...OBJECTIVE:To investigate the protective effects of Zuogui Wan(左归丸,ZGW)on bone loss induced by ovariectomy(OVX)and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model.METHODS:Fifty Sprague-Dawley female rats were randomly divided into sham-operated(sham)group and four OVX subgroups.Rats subjected to sham and OVX were treated with the vehicle(OVX,1 mL/100 g weight,n=10),17β-estradiol(E2,50μg·kg-1·d-1),and ZGW at the doses of 2.3(ZGW-L)and 4.6(ZGW-H)g/kg/day lyophilized powder daily for 3 months,respectively.The serum biochemical parameters of 17β-estrogen(17β-E2),tartrate-resistant acid phosphatase(TRACP-5 b)and bone alkaline phosphatase(BALP)were measured by enzyme-linked immunosorbent assay.Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones.Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur.The gene or protein expression of orexin-A,orexin receptor 1(OX1R),orexin receptor 2(OX2R),osteoprotegerin(OPG)and receptor activator of nuclear factor-κB ligand(RANKL)were assayed by either quantitative polymerase chain reaction or Western blot analysis.RESULTS:Compared with the OVX group,ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and 17β-E2(P<0.01).Meanwhile,ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number,and arranging the trabeculae structure properly.Compared with the OVX group,it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae,and OPG in the tibiae of ZGW groups(P<0.01,<0.05),while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae(P<0.01).CONCLUSION:ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.展开更多
选取苏钟种母猪16头,在第2个发情期后,按发情前期、发情期、发情后期和间情期随机分成4组。用RT-PCR检测苏钟猪发情周期不同时期preproorexin和orexin 1受体(OX1R) m RNA在下丘脑-垂体-卵巢轴中的表达。结果显示:发情周期不同时期prepro...选取苏钟种母猪16头,在第2个发情期后,按发情前期、发情期、发情后期和间情期随机分成4组。用RT-PCR检测苏钟猪发情周期不同时期preproorexin和orexin 1受体(OX1R) m RNA在下丘脑-垂体-卵巢轴中的表达。结果显示:发情周期不同时期preproorexin m RNA在下丘脑、垂体和卵巢中变化趋势一致,preproorexin m RNA在猪的发情前期表达最高,随后其表达量开始下降,在发情后期其表达最少,在间情期时又开始上升。下丘脑中OX1R m RNA在发情前期开始上升,在发情后期达到最高,随后在间情期又开始下降。垂体和卵巢中OX1 R m RNA的变化与下丘脑中OX1R m RNA的变化趋势一致。上述结果表明:orexin可能参与调控动物生殖过程。展开更多
基金supported by the Natural Science Foundation of China,No.81260295the Graduate Student Innovation Fund of Jiangxi Province of China,No.YC2015-S090
文摘Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.
基金supported by grants from the National Natural Science Foundation of China (Grants No. 31800971 and 81873654)
文摘Orexin signaling has been associated with energy expenditure and brown adipose tissue(BAT)function.However,conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis.In this study,we show that a specific orexin receptor type 2(OX2R)agonist[Ala11,D-Leu15]-OxB(OB-Ala)inhibited intrascapular brown adipose tissue(iBAT)thermogenesis by reducing sympathetic output to iBAT.This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself.Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus.Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop.Our study uncovers a novel primary action site of orexin in the regulation of energy balance.
基金Supported by Traditional Chinese and Western Medicine Clinical Medicine Brand Construction Project of Jiangsu Higher Education Institutions(PhaseⅡ)National Natural Science Foundation of China(No.81573874 and81873229)。
文摘OBJECTIVE:To investigate the protective effects of Zuogui Wan(左归丸,ZGW)on bone loss induced by ovariectomy(OVX)and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model.METHODS:Fifty Sprague-Dawley female rats were randomly divided into sham-operated(sham)group and four OVX subgroups.Rats subjected to sham and OVX were treated with the vehicle(OVX,1 mL/100 g weight,n=10),17β-estradiol(E2,50μg·kg-1·d-1),and ZGW at the doses of 2.3(ZGW-L)and 4.6(ZGW-H)g/kg/day lyophilized powder daily for 3 months,respectively.The serum biochemical parameters of 17β-estrogen(17β-E2),tartrate-resistant acid phosphatase(TRACP-5 b)and bone alkaline phosphatase(BALP)were measured by enzyme-linked immunosorbent assay.Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones.Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur.The gene or protein expression of orexin-A,orexin receptor 1(OX1R),orexin receptor 2(OX2R),osteoprotegerin(OPG)and receptor activator of nuclear factor-κB ligand(RANKL)were assayed by either quantitative polymerase chain reaction or Western blot analysis.RESULTS:Compared with the OVX group,ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and 17β-E2(P<0.01).Meanwhile,ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number,and arranging the trabeculae structure properly.Compared with the OVX group,it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae,and OPG in the tibiae of ZGW groups(P<0.01,<0.05),while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae(P<0.01).CONCLUSION:ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.
文摘选取苏钟种母猪16头,在第2个发情期后,按发情前期、发情期、发情后期和间情期随机分成4组。用RT-PCR检测苏钟猪发情周期不同时期preproorexin和orexin 1受体(OX1R) m RNA在下丘脑-垂体-卵巢轴中的表达。结果显示:发情周期不同时期preproorexin m RNA在下丘脑、垂体和卵巢中变化趋势一致,preproorexin m RNA在猪的发情前期表达最高,随后其表达量开始下降,在发情后期其表达最少,在间情期时又开始上升。下丘脑中OX1R m RNA在发情前期开始上升,在发情后期达到最高,随后在间情期又开始下降。垂体和卵巢中OX1 R m RNA的变化与下丘脑中OX1R m RNA的变化趋势一致。上述结果表明:orexin可能参与调控动物生殖过程。
