In the face of constantly changing environments,the central nervous system(CNS)rapidly and accurately calculates the body's needs,regulates feeding behavior,and maintains energy homeostasis.The arcuate nucleus of ...In the face of constantly changing environments,the central nervous system(CNS)rapidly and accurately calculates the body's needs,regulates feeding behavior,and maintains energy homeostasis.The arcuate nucleus of the hypothalamus(ARC)plays a key role in this process,serv-ing as a critical brain region for detecting nutrition-related hormones and regulating appetite and energy homeostasis.Agouti-related protein(AgRP)/neuropeptide Y(NPY)neu-rons in the ARC are core elements that interact with other brain regions through a complex appetite-regulating network to comprehensively control energy homeostasis.In this review,we explore the discovery and research progress of AgRP neurons in regulating feeding and energy metabolism.In addition,recent advances in terms of feeding behavior and energy homeostasis,along with the redundant neural mecha-nisms involved in energy metabolism,are discussed.Finally,the challenges and opportunities in the field of neural regula-tion of feeding and energy metabolism are briefly discussed.展开更多
The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C_(42)H_(72)O_(14)),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intrap...Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C_(42)H_(72)O_(14)),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to100 mg/kg.Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles.Further,orexin neurons in the lateral hypothalamus(LH)and corticotropin-releasing hormone(CRH)neurons in the paraventricular hypothalamic nucleus(PVH)were ablated using viral vector surgery and electrode embedding.The excitability of LH^(orexin)and PVH^(CRH)neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog(c-Fos)expression.Results:Rg1(12.5–100 mg/kg)augmented the duration of non-rapid eye movement(NREM)sleep phases,while reducing the duration of wakefulness,in a dose dependent manner.The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time.We found that these sleep-promoting effects were weakened in the LH^(orexin)and PVH^(CRH)neuron ablation groups,and disappeared in the orexin and CRH double-ablation group.Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons.Conclusion:Rg1 increases the duration of NREM sleep,underscoring the essential roles of LH^(orexin)and PVH^(CRH)neurons in facilitating the sleep-promoting effects of Rg1.Please cite this article as:Wang YY,Wu Y,Yu KW,Xie HY,Gui Y,Chen CR,Wang NH.Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus.J Integr Med.2024;22(6):719–728.展开更多
Objective To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin （EM） on the regulation of gastric motility in diabetic rats. Met...Objective To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin （EM） on the regulation of gastric motility in diabetic rats. Methods The motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals. Results Diabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular （PVN） and supraoptic nuclei （SON） of the hypothalamus in the diabetic rats. Intracerebroventricular （i.c.v.） administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM （91.56 nmol, i.c.v.） dose-dependently increased the amplitude by （174.82±48.62）% （P 〈 0.05）, and increased the frequency by （70.43±27.11）% （P 〈 0.05） in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109. Conclusion Motilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.展开更多
Effects of acupuncture on the spontaneous discharge of nerve cells and levels of monoamine neurotransmitters in ventromedial nucleus of hypothalamus (VMH) of the obese rats were investigated. Results indicated that th...Effects of acupuncture on the spontaneous discharge of nerve cells and levels of monoamine neurotransmitters in ventromedial nucleus of hypothalamus (VMH) of the obese rats were investigated. Results indicated that the levels of tyrosine (Tyr) and dopamine (DA) were lowered, the levels of 5-hydroxytryptamine (5-HT) and 5-hydoxyindole acetic acid (5-HIAA) increased, and the frequency of the spontaneous discharge of nerve cells in VMH lowered in the obese rat group as compared with the normal group. When acupuncture obtained the effect of weight reduction, the frequency of spontaneous discharges of nerve cells in VMH were markedly increased, and the levels of Tyr, DA and tryptamine (Typ) and 5-HT/5-HIAA ratio elevated, and the 5-HT level lowered. It is suggested that the virtuous regulative action of acupuncture on VMH might be one of the key factors in acupuncture for weight reduction.展开更多
Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regul...Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regulated sleep homeostasis. Orexin A induces a robust increase in the firing activity of orexin neurons, while adenosine has an inhibitory effect. Whether the excitatory action of orexins in the lateral hypothalamus actually promotes wakefulness and reverses the sleep-producing effect of adenosine in vivo is less clear. In this study, electroencephalographic and electromyographic recordings were used to investigate the effects of orexin A and adenosine on sleep and wakefulness in rats. We found that microinjection of orexin A into the lateral hypothalamus increased wakefulness with a concomitant reduction of sleep during the first 3 h of post-injection recording, and this was completely blocked by a selective antagonist for orexin receptor 1, SB 334867. The enhancement of wakefulness also occurred after application of the excitatory neurotransmitter glutamate in the first 3 h post-injection. However, in the presence of the NMDA receptor antagonist APV, orexin A did not induce any change of sleep and wakefulness in the first 3 h. Further, exogenous application of adenosine into the lateral hypothalamus induced a marked increase of sleep in the first 3-h post-injection. No significant change in sleep and wakefulness was detected after adenosine application followed by orexin A administration into the same brain area. Thesefindings suggest that the sleep-promoting action of adenosine can be reversed by orexin A applied to the lateral hypothalamus, perhaps by exciting glutamatergic input to orexin neurons via the action of orexin receptor 1.展开更多
In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobili...In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.展开更多
Background： Heat stress has resulted in great losses in poultry production. To address this issue, we systematically analyzed chicken hypothalamus transcriptome responses to thermal stress using a 44 k chicken Agilen...Background： Heat stress has resulted in great losses in poultry production. To address this issue, we systematically analyzed chicken hypothalamus transcriptome responses to thermal stress using a 44 k chicken Agilent microarray, Methods： Hypothalamus samples were collected from a control group reared at 25℃, a heat-stress group treated at 34℃ for 24 h, and a temperature-recovery group reared at 25℃ for 24 h following a heat-stress treatment. We compared the expression profiles between each pair of the three groups using microarray data. Results： A total of 1,967 probe sets were found to be differentially expressed in the three comparisons with P 〈 0.05 and a fold change （FC） higher than 1.5, and the genes were mainly involved in self-regulation and compensation required to maintain homeostasis. Consistent expression results were found for 11 selected genes by quantitative real-time PCR. Thirty-eight interesting differential expression genes were found from GO term annotation and those genes were related to meat quality, growth, and crucial enzymes. Using these genes for genetic network analysis, we obtained three genetic networks. Moreover, the transcripts of heat-shock protein, including Hsp 40 and Hsp 90, were significantly altered in response to thermal stress. Conclusions： This study provides a broader understanding of molecular mechanisms underlying stress response in chickens and discovery of novel genes that are regulated in a specific thermal-stress manner.展开更多
OBJECTIVE: To investigate changes in gene expression profiles in the hypothalamus related to the effects of acupuncture at the Renying(ST 9) acupoint in spontaneously hypertensive(SH) rats.METHODS: We randomly divided...OBJECTIVE: To investigate changes in gene expression profiles in the hypothalamus related to the effects of acupuncture at the Renying(ST 9) acupoint in spontaneously hypertensive(SH) rats.METHODS: We randomly divided 18 SH rats into Renying(ST 9) group and model control group, 9 body weight-matched Wistar-Kyoto rats were used as blank controls. Acupuncture was performed manually for 20-min daily over 28 d in the Renying(ST 9) group. Rat Gene 2.0 array technology was used for the determination of gene expression profiles and the screened key genes were verified by real-time quantitative polymerase chain reaction(RT-PCR) analyses.RESULTS: The different groups exhibited differential gene expression: compared with the blank control group, 48 genes were up-regulated and 91 genes were down-regulated in the model group;compared with the model group, 79 genes were up-regulated and 80 genes were down-regulated in Renying(ST 9) group. The RT-PCR results of the key genes including Chi3 l1, Ephx2, Klk1, 5-HT1 A and Cbs were consistent with that of gene chip analysis.CONCLUTION: Acupuncture at Renying(ST 9)could significantly lower the blood pressure of SH rats and affect their hypothalamic gene expression profile. Genes associated with the contraction of vascular smooth muscle and the regulation of inflammation, neurotransmitters may be involved in acupuncture's antihypertensive mechanism.展开更多
AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabe...AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabetes Sprague-Dawley(SD) rats, 6 wk of age, fed with high-sugar and highfat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group(S0 group, n = 10), sham operation group(Sh group, n = 10) and sleeve gastrectomy group(SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test(OGTT), acylated ghrelin(AG) and total ghrelin(TG) were collected and measured at the first day(when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The m RNA expression of preproghrelin, GOAT and neuropeptide Y(NPY), and protein expression of ghrelin, GOAT, GHSR and the m TOR pathway(p-Akt, p-m TOR and p-S6) were measured in the hypothalamus.RESULTS SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG(1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG(153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group(0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed m RNA and protein levels of preproghrelin(0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT(0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY m RNA expression(0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-m TOR and p-S6 were higher in the SG group, which indicated that the hypothalamic m TOR pathway was activated after SG at the postoperative week 8. CONCLUSION The reduction of ghrelin expression and activation of the m TOR pathway might have opposite effects on food intake, as SG improves obesity and T2 DM.展开更多
Neuropeptide Y （NPY） is one of the most important orexigenic agents in central regulation of feeding behavior, body weight and energy homeostasis in domestic chickens. To examine differences in the hypothalamic NPY ...Neuropeptide Y （NPY） is one of the most important orexigenic agents in central regulation of feeding behavior, body weight and energy homeostasis in domestic chickens. To examine differences in the hypothalamic NPY between layer-type and meat-type of chickens, which are two divergent kinds of the domestic chickens in feeding behavior and body weight, we detected mRNA levels of NPY in hypothalamic infundibular nucleus （IN）, paraventricular nucleus （PVN） and lateral hypothalamic area （LHA） of these two types of chickens using one-step real time RT-PCR. The meat-type chicken had more food daily （about 1.7 folds） and greater body weights （about 1.5 folds） and brain weights than the layer-type chicken at the age of 14 d. In the meat-type of chicken, NPY mRNA levels of the IN and PVN were significantly greater than those of the LHA, and were not significantly different between the lN and PVN. However, in the layer-type of chicken, NPY mRNA levels were significantly greater in the IN than those in the LHA and PVN, and were not significantly different between the PVN and LHA. In all these hypothalamic regions the layer-type of chicken had significantly higher NPY mRNA levels than the meat-type chicken did. These results suggest the expression of NPY in the hypothalamus has a type-dependent pattern in domestic chickens.展开更多
Objective To explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation. Methods Fifty-four female rats were randomly assigned to 6 groups： one sham-operate...Objective To explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation. Methods Fifty-four female rats were randomly assigned to 6 groups： one sham-operated group （SHAM）, one ovariectomized （OVX） control group, three OVX groups fed with 400 ppm （L-SI）, 1 200 ppm （M-SI） and 3 600 ppm （H-SI） isoflavone respectively, and one OVX group receiving 0.45 ppm diethylstilbestrol （EC）. All rats were allowed to take high-fat diet for 4 weeks. Some neuropeptides were measured by RT-PCR. These neuropeptides included NPY, pro-opiomelanocortin （POMC）, cocaine and amphetamine regulated transcript （CART）, orexin, melanin-concentrating hormone （MCH）, ting hormone precursor （P-MCH）, ghrelin, and leptin. Results Compared with the OVX control group, the body weight and food intake in the H-S1 group were reduced significantly and there was a significant dose-dependent manner in the 3 isoflavone groups. The results of RT-PCR showed that the NPY level in the 3 isoflavone groups was significantly increased and the POMC/CART gene expression decreased significantly in rats＇ hypothalamus compared with that in the OVX control group. However, the expression of orexin, MCH and P-MCH had no change. The peripheral grelin mRNA expression was higher in the 3 isoflavone groups, while leptin gene expression in the fat was not consistent. Conclusions This research showed that isoflavone could prevent obesity induced by high-fat diet and ovariectomy through regulating hypothalamus and peripheral orexigenic gene expressions associated with food intake.展开更多
Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere- broventricular dose of ...Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere- broventricular dose of metformin and compound C, in a broader attempt to investigate the regula- tory effects of metformin on food intake and to explore the possible mechanism. Results showed that central administration of metformin significantly reduced food intake and body weight gain, par- ticularly after 4 hours. A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase. Furthermore, metformin also improved lipid metabolism by reducing plasma low-density lipoprotein. Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres- sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.展开更多
Objective:To probe into the most effective site,extra-ordinary point,acupoint and channel for regulating reproductive endocrine function by means of the study on acupuncture activating the gonadotropin-releasing hormo...Objective:To probe into the most effective site,extra-ordinary point,acupoint and channel for regulating reproductive endocrine function by means of the study on acupuncture activating the gonadotropin-releasing hormone neurons(GnRH) in hypothalamus.Methods:Female SD rats of reproductive age were used,and the in vivo study on GnRH neurons in hypothalamus was made with mimic sexual stimulation and feedback regulation.The neuron-activating effects of the acupoints on the channels pertaining to the zang-and fu-organs related with reproductive endocrine and the extra-ordinary points in different regions were studied using the discharge of the neuron as index,and then the neurons were labeled with horseradish peroxidase(HRP) .Results:Acupuncture was given at two acupoints each on the three yin channels of foot,the three yang channels of foot,the Conception Vessel and the Governor Vessel.The order of the mean increasing percentage in the hypothalamic GnRH neuron electric activity was:the Gallbladder Channel>the Spleen Channel>the Stomach Channel/the Bladder Channel/the Conception Vessel>the Liver Channel>the Kidney Channel>the Governor Vessel;for different acupoints,it was:Guanyuan(CV 4) >Sanyinjiao(SP 6) >Zusanli(ST 36) >Daimai(GB 26) /Yanglingquan(GB 34) >Shenshu(BL 23) >Weizhong(BL 40) >Yaoyangguan(GV 3) /Liangmen(ST 21) /Fujie(SP 14) >Qimen(LR 14) /Yingu(KI 10) >Tangzhong(CV 17) /Zhiyang(GV 9) ;for different positions,it was:the lower abdominal part/the lower limb part>the thoracodorsal part;for the extra-ordinary points,it was:Zigong(EX-CA1) >Dannang(EX-LE6) /Yaoyan(EX-B7) >Baichongwo(EX-LE3) /Qianzheng>Jingbi/Bizhong/Taiyang(EX-HN5) >Erbai(EX-UE2) /Dingchun;and for the distribution sites of the extra-ordinary points:lower abdominal region>the lower limb region>the craniofacial region>the upper limb region/the thoracodorsal region.Conclusion:For regulating the reproductive endocrine function,the acupoints located at the same neural segment with the reproductive organ should be selected as the main points,and it is necessary to combine with syndrome differentiation of the viscera and channels.展开更多
Background： In mammals, leptin is an attractive candidate for mediating the metabolic signal and the reproductive function via the specific receptor in hypothalamus. However, till now, the role of leptin on reproduct...Background： In mammals, leptin is an attractive candidate for mediating the metabolic signal and the reproductive function via the specific receptor in hypothalamus. However, till now, the role of leptin on reproduction in birds is less well established. This experiment was conducted to elucidate the role of leptin on the onset of reproduction in bird, as a first step, to detect the changes of peripheral leptin and leptin receptor mRNA expression in hypothalamus between mature and immature hens at the same age. 120 ISA brown pullets at D60 were allocated randomly into two groups, long light （LL） group being raised under artificial light regimes with incrementally increased light phase （from 8 L：]6D to 14 L：]2D） and short light （SL） group raised on consistent light （8 L：16D） for 12 wk. Results： The results showed that pullets in LL group reached sexual maturation 15 d earlier than those in SL group. Serum E2 showed a significant increase with age, but no difference was observed between two groups. Serum leptin concentration decreased significantly from D112 to D136 in LL, and was markedly higher in LL group than that in SL at D112, while there was no significant difference between two groups at D136. Leptin receptor and GnRH-I mRNA expression in hypothalamus were significantly increased with age, yet there was no significant difference between SL and LL chickens at the same age. The expression of FSH-13 and LH-13 mRNA in pituitary was increased with age but did not show significant difference between LL and gland, and decreased from D112 to D136 in LL but not groups at the same age. SL group. GnfiH-I mRNA expression was very rich in pinea n SL group, and there was no difference between two Conclusions： These results indicate that the earlier sexual maturation in hens induced by long-light regime is not accompanied with an increase in serum leptin or leptin receptor gene expression in hypothalamus, or genes expression in HPG axis.展开更多
This study tested the effects of the gastrointestinal pulse train electrical stimulation with different parameters and at different locations on the neuronal activities of the lateral hypothalamus area（LHA） in obese...This study tested the effects of the gastrointestinal pulse train electrical stimulation with different parameters and at different locations on the neuronal activities of the lateral hypothalamus area（LHA） in obese rats in order to find the optimal stimulation parameter and location. Eight gastric electrical stimulations（GES） with different parameters were performed and the neuronal activities of gastric-distension responsive（GD-R） neurons in LHA were observed. The effects of stimulations with 8 parameters were compared to find the optimal parameter. Then the optimal parameter was used to perform electrical stimulation at duodenum and ileum, and the effects of the duodenal and ileac stimulation on the GD-R neurons in LHA were compared with the gastric stimulation of optimal parameter. The results showed that GES with the lowest energy parameter（0.3 ms, 3 mA, 20 Hz, 2 s on, 3 s off） activated the least neurons. The effects of GES with other parameters whose pulse width was 0.3 ms were not significantly different from those of the lowest energy parameter. Most gastric stimulations whose pulse width was 3 ms activated more LHA neurons than the smallest energy parameter stimulation, and the effects of those 3 ms gastric stimulations were similar. Accordingly, the lowest energy parameter was recognized as the optimal parameter. The effects of stimulations with the optimal parameter at stomach, duodenum and ileum on the LHA neuronal activities were not different. Collectively, gastrointestinal electrical stimulation（GIES） with relatively large pulse width might have stronger effects to the neuronal activities of GD-R neurons in LHA of obese rats. The effects of the GIES at different locations（stomach, duodenum and ileum） on those neurons are similar, and GES is preferential because of its easy clinical performance and safety.展开更多
There have been fairly good effects ofDecoction Rehmannia(地黄饮子)in treat-ing stroke syndromes.The model of theexperimental cerebral embolism has been es-tablished and the morphological andcytochemical changes of th...There have been fairly good effects ofDecoction Rehmannia(地黄饮子)in treat-ing stroke syndromes.The model of theexperimental cerebral embolism has been es-tablished and the morphological andcytochemical changes of the effect of展开更多
Background:Corticotropin-releasing hormone(CRH),the major secretagogue of the hypothalamic-pituitary-adrenal(HPA)axis,is intricately intertwined with the clock genes to regulate the circadian rhythm of various body fu...Background:Corticotropin-releasing hormone(CRH),the major secretagogue of the hypothalamic-pituitary-adrenal(HPA)axis,is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions.N6-methyladenosine(m^(6)A)RNA methylation is involved in the regulation of circadian rhythm,yet it remains unknown whether CRH expression and m^(6)A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress.Results:Chronic exposure to corticosterone(CORT)eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken.The circadian rhythms of clock genes in hippocampus,hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens.The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened,together with mRNA of other feeding-related neuropeptides.Interestingly,hypothalamic m^(6)A level oscillates in an opposite pattern to CRH mRNA,with lowestm^(6)A level after midnight(ZT18)corresponding to the peak of CRH mRNA before dawn(ZT22).CORT diminished the circadian rhythm of m^(6)A methylation with significantly increased level at night.Further site-specific m^(6)A analysis on 3’UTR of CRH mRNA indicates that higher m^(6)A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night(ZT18 and ZT22).Conclusions:Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus,leading to dysfunction of HPA axis in the chicken.RNA m^(6)A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions.展开更多
In the present study, we reported distribution of ERα and ER β mRNAs in the hypothalamus of young and old ovariectomized （OVX） rhesus macaques. The ERα were detected in all six major vestiblular nuclei which incl...In the present study, we reported distribution of ERα and ER β mRNAs in the hypothalamus of young and old ovariectomized （OVX） rhesus macaques. The ERα were detected in all six major vestiblular nuclei which included arcuate nucleus （ARC） , paraventricularis nucleus （PVN） , periventricular nucleus （PeriV） , supraoptic nucleus （SON）, medial prioptic nucleus （MPN） and lateral hypotbalamus area （LHA）. However, the ERβ mRNA can also detected in those nuclei excerpt SON, but the signals of ERβ mRNA were weaker than those of ERα mRNA. We observed that the degree of expression of ERs mRNA were different in most nucleus of old and young monkeys. The ERα mRNAs were highly expressed in ARC and SON in young monkeys compared with old monkeys. Moderate amount of ERα mRNAs hybridization signals and weak signals were observed in LHA, and MPN both in young and old monkeys. In contrast, only lower level of ERα hybridization signal were observed in PVN and PeriV in young monkeys, and the signals of ERα were very low in those nucleus of old monkeys. In general, the expression of ERβ mRNA were weaker than that of ERα mRNA in above nucleus excerpt LHA. The relatively higher density of ERβ hybridization signals have been observed in the LHA in young monkey compared with old monkeys. Low amount of. ERβ mRNA hybridization signals were observed in the ARC, PVN and MPN, and no age differences were seen in PVN and MPN of those monkeys. In PeriV, we observed some signals in young monkey and a few signals in old monkeys. It was different from the rodent in which we did not found ERβ hybridization signal in SON. This study showed that both of the two estrogen receptors not only had the same pattern of expression but also had many different patterns of expression. The different expression of ERα and ERβ mRNAs in the young and old monkey brain may imply diverse functions in different regions of the monkey brain.展开更多
Leptin deficiency is principally linked to metabolic disorders. Leptin knockout（Lep△I14/△I14 Sprague Dawley rats created by CRISPR/Cas9 is a new model to study metabolic disorders. We used a whole rat genome oligon...Leptin deficiency is principally linked to metabolic disorders. Leptin knockout（Lep△I14/△I14 Sprague Dawley rats created by CRISPR/Cas9 is a new model to study metabolic disorders. We used a whole rat genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of the white adipose tissue, liver and hypothalamus in Lep△I14/△I14）and wild-type（WT） rats. We found 1,651 differentially expressed（enriched） genes in white adipose tissue,916 in the liver, and 306 in the hypothalamus in the Lep△I14/△I14 rats compared to WT. Gene ontology category and KEGG pathway analysis of the relationships among differentially expressed genes showed that these genes were represented in a variety of functional categories, including fatty acid metabolism, molecular transducers and cellular processes. The reliability of the data obtained from microarray was verified by quantitative real-time PCR on 14 representative genes. These data will contribute to a greater understanding of different metabolic disorders, such as obesity and diabetes.展开更多
基金supported by Grants from the Research Funds of the Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20220018)the National Natural Science Foundation of China(31822026,32271063,31500860,and 32100821)the National Science and Technology Innovation 2030 Major Project of China(2021ZD0203900).
文摘In the face of constantly changing environments,the central nervous system(CNS)rapidly and accurately calculates the body's needs,regulates feeding behavior,and maintains energy homeostasis.The arcuate nucleus of the hypothalamus(ARC)plays a key role in this process,serv-ing as a critical brain region for detecting nutrition-related hormones and regulating appetite and energy homeostasis.Agouti-related protein(AgRP)/neuropeptide Y(NPY)neu-rons in the ARC are core elements that interact with other brain regions through a complex appetite-regulating network to comprehensively control energy homeostasis.In this review,we explore the discovery and research progress of AgRP neurons in regulating feeding and energy metabolism.In addition,recent advances in terms of feeding behavior and energy homeostasis,along with the redundant neural mecha-nisms involved in energy metabolism,are discussed.Finally,the challenges and opportunities in the field of neural regula-tion of feeding and energy metabolism are briefly discussed.
文摘The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
基金supported by grants from the National Natural Science Foundation of China(No.82174496,No.82374574)Shanghai Key Discipline of Traditional Chinese Medicine Construction Project(No.shzyyzdxk–2024113)。
文摘Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C_(42)H_(72)O_(14)),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to100 mg/kg.Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles.Further,orexin neurons in the lateral hypothalamus(LH)and corticotropin-releasing hormone(CRH)neurons in the paraventricular hypothalamic nucleus(PVH)were ablated using viral vector surgery and electrode embedding.The excitability of LH^(orexin)and PVH^(CRH)neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog(c-Fos)expression.Results:Rg1(12.5–100 mg/kg)augmented the duration of non-rapid eye movement(NREM)sleep phases,while reducing the duration of wakefulness,in a dose dependent manner.The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time.We found that these sleep-promoting effects were weakened in the LH^(orexin)and PVH^(CRH)neuron ablation groups,and disappeared in the orexin and CRH double-ablation group.Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons.Conclusion:Rg1 increases the duration of NREM sleep,underscoring the essential roles of LH^(orexin)and PVH^(CRH)neurons in facilitating the sleep-promoting effects of Rg1.Please cite this article as:Wang YY,Wu Y,Yu KW,Xie HY,Gui Y,Chen CR,Wang NH.Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus.J Integr Med.2024;22(6):719–728.
基金This work was supported by the National Natural Science Foundation of China(No.30370467)the Bilateral Scientific and Technological Cooperation between Flanders and China(Contract BIL01/13).
文摘Objective To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin （EM） on the regulation of gastric motility in diabetic rats. Methods The motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals. Results Diabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular （PVN） and supraoptic nuclei （SON） of the hypothalamus in the diabetic rats. Intracerebroventricular （i.c.v.） administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM （91.56 nmol, i.c.v.） dose-dependently increased the amplitude by （174.82±48.62）% （P 〈 0.05）, and increased the frequency by （70.43±27.11）% （P 〈 0.05） in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109. Conclusion Motilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.
文摘Effects of acupuncture on the spontaneous discharge of nerve cells and levels of monoamine neurotransmitters in ventromedial nucleus of hypothalamus (VMH) of the obese rats were investigated. Results indicated that the levels of tyrosine (Tyr) and dopamine (DA) were lowered, the levels of 5-hydroxytryptamine (5-HT) and 5-hydoxyindole acetic acid (5-HIAA) increased, and the frequency of the spontaneous discharge of nerve cells in VMH lowered in the obese rat group as compared with the normal group. When acupuncture obtained the effect of weight reduction, the frequency of spontaneous discharges of nerve cells in VMH were markedly increased, and the levels of Tyr, DA and tryptamine (Typ) and 5-HT/5-HIAA ratio elevated, and the 5-HT level lowered. It is suggested that the virtuous regulative action of acupuncture on VMH might be one of the key factors in acupuncture for weight reduction.
基金supported by the National Natural Science Foundation of China(81071074)
文摘Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regulated sleep homeostasis. Orexin A induces a robust increase in the firing activity of orexin neurons, while adenosine has an inhibitory effect. Whether the excitatory action of orexins in the lateral hypothalamus actually promotes wakefulness and reverses the sleep-producing effect of adenosine in vivo is less clear. In this study, electroencephalographic and electromyographic recordings were used to investigate the effects of orexin A and adenosine on sleep and wakefulness in rats. We found that microinjection of orexin A into the lateral hypothalamus increased wakefulness with a concomitant reduction of sleep during the first 3 h of post-injection recording, and this was completely blocked by a selective antagonist for orexin receptor 1, SB 334867. The enhancement of wakefulness also occurred after application of the excitatory neurotransmitter glutamate in the first 3 h post-injection. However, in the presence of the NMDA receptor antagonist APV, orexin A did not induce any change of sleep and wakefulness in the first 3 h. Further, exogenous application of adenosine into the lateral hypothalamus induced a marked increase of sleep in the first 3-h post-injection. No significant change in sleep and wakefulness was detected after adenosine application followed by orexin A administration into the same brain area. Thesefindings suggest that the sleep-promoting action of adenosine can be reversed by orexin A applied to the lateral hypothalamus, perhaps by exciting glutamatergic input to orexin neurons via the action of orexin receptor 1.
基金supported by the National Natural Science Foundation of China,No.30672578,81072756and81202644China National Funds for Distinguished Young Scientists,No.30825046+2 种基金Program for Innovative Research Team in Beijing University of Chinese Medicine,No.2011CXTD-07Program for University Key Teacher of Hebei Medical UniversitySpecialized Research Fund for the Doctoral Program of Higher Education,No.20121323120016
文摘In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.
基金financially supported by Beijing innovation team attached to poultry industry technology system(CARS-PSTP)
文摘Background： Heat stress has resulted in great losses in poultry production. To address this issue, we systematically analyzed chicken hypothalamus transcriptome responses to thermal stress using a 44 k chicken Agilent microarray, Methods： Hypothalamus samples were collected from a control group reared at 25℃, a heat-stress group treated at 34℃ for 24 h, and a temperature-recovery group reared at 25℃ for 24 h following a heat-stress treatment. We compared the expression profiles between each pair of the three groups using microarray data. Results： A total of 1,967 probe sets were found to be differentially expressed in the three comparisons with P 〈 0.05 and a fold change （FC） higher than 1.5, and the genes were mainly involved in self-regulation and compensation required to maintain homeostasis. Consistent expression results were found for 11 selected genes by quantitative real-time PCR. Thirty-eight interesting differential expression genes were found from GO term annotation and those genes were related to meat quality, growth, and crucial enzymes. Using these genes for genetic network analysis, we obtained three genetic networks. Moreover, the transcripts of heat-shock protein, including Hsp 40 and Hsp 90, were significantly altered in response to thermal stress. Conclusions： This study provides a broader understanding of molecular mechanisms underlying stress response in chickens and discovery of novel genes that are regulated in a specific thermal-stress manner.
基金Supported by a Grant from the State Administration of Traditional Chinese Medicine Industry Subject:the Study and Application of Acupuncture in the Prevention and Treatment of Stroke of the Primary Hypertension(No.201507001-08)
文摘OBJECTIVE: To investigate changes in gene expression profiles in the hypothalamus related to the effects of acupuncture at the Renying(ST 9) acupoint in spontaneously hypertensive(SH) rats.METHODS: We randomly divided 18 SH rats into Renying(ST 9) group and model control group, 9 body weight-matched Wistar-Kyoto rats were used as blank controls. Acupuncture was performed manually for 20-min daily over 28 d in the Renying(ST 9) group. Rat Gene 2.0 array technology was used for the determination of gene expression profiles and the screened key genes were verified by real-time quantitative polymerase chain reaction(RT-PCR) analyses.RESULTS: The different groups exhibited differential gene expression: compared with the blank control group, 48 genes were up-regulated and 91 genes were down-regulated in the model group;compared with the model group, 79 genes were up-regulated and 80 genes were down-regulated in Renying(ST 9) group. The RT-PCR results of the key genes including Chi3 l1, Ephx2, Klk1, 5-HT1 A and Cbs were consistent with that of gene chip analysis.CONCLUTION: Acupuncture at Renying(ST 9)could significantly lower the blood pressure of SH rats and affect their hypothalamic gene expression profile. Genes associated with the contraction of vascular smooth muscle and the regulation of inflammation, neurotransmitters may be involved in acupuncture's antihypertensive mechanism.
基金Supported by the National Natural Science Foundation of China,No.81270969(to Wei Zhang)and No.81300723(to Cheng-Xiang Shan)Shanghai Science and Technology Commission,No.12ZR1439100(to Wei Zhang)
文摘AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabetes Sprague-Dawley(SD) rats, 6 wk of age, fed with high-sugar and highfat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group(S0 group, n = 10), sham operation group(Sh group, n = 10) and sleeve gastrectomy group(SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test(OGTT), acylated ghrelin(AG) and total ghrelin(TG) were collected and measured at the first day(when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The m RNA expression of preproghrelin, GOAT and neuropeptide Y(NPY), and protein expression of ghrelin, GOAT, GHSR and the m TOR pathway(p-Akt, p-m TOR and p-S6) were measured in the hypothalamus.RESULTS SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG(1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG(153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group(0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed m RNA and protein levels of preproghrelin(0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT(0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY m RNA expression(0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-m TOR and p-S6 were higher in the SG group, which indicated that the hypothalamic m TOR pathway was activated after SG at the postoperative week 8. CONCLUSION The reduction of ghrelin expression and activation of the m TOR pathway might have opposite effects on food intake, as SG improves obesity and T2 DM.
基金Project supported by the Natural Science Foundation of ZhejiangProvince (No. Y306220)the Scientific Research Startup Fund ofZhejiang Academy of Agricultural Sciences, China
文摘Neuropeptide Y （NPY） is one of the most important orexigenic agents in central regulation of feeding behavior, body weight and energy homeostasis in domestic chickens. To examine differences in the hypothalamic NPY between layer-type and meat-type of chickens, which are two divergent kinds of the domestic chickens in feeding behavior and body weight, we detected mRNA levels of NPY in hypothalamic infundibular nucleus （IN）, paraventricular nucleus （PVN） and lateral hypothalamic area （LHA） of these two types of chickens using one-step real time RT-PCR. The meat-type chicken had more food daily （about 1.7 folds） and greater body weights （about 1.5 folds） and brain weights than the layer-type chicken at the age of 14 d. In the meat-type of chicken, NPY mRNA levels of the IN and PVN were significantly greater than those of the LHA, and were not significantly different between the lN and PVN. However, in the layer-type of chicken, NPY mRNA levels were significantly greater in the IN than those in the LHA and PVN, and were not significantly different between the PVN and LHA. In all these hypothalamic regions the layer-type of chicken had significantly higher NPY mRNA levels than the meat-type chicken did. These results suggest the expression of NPY in the hypothalamus has a type-dependent pattern in domestic chickens.
基金Supported by the Natural Science Foundation of China (30671755)the Health Department-funded projects of Heilongjiang province (2006-300)the Innovative Foundation of the Harbin Medical University in China (HCXS2008006)
文摘Objective To explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation. Methods Fifty-four female rats were randomly assigned to 6 groups： one sham-operated group （SHAM）, one ovariectomized （OVX） control group, three OVX groups fed with 400 ppm （L-SI）, 1 200 ppm （M-SI） and 3 600 ppm （H-SI） isoflavone respectively, and one OVX group receiving 0.45 ppm diethylstilbestrol （EC）. All rats were allowed to take high-fat diet for 4 weeks. Some neuropeptides were measured by RT-PCR. These neuropeptides included NPY, pro-opiomelanocortin （POMC）, cocaine and amphetamine regulated transcript （CART）, orexin, melanin-concentrating hormone （MCH）, ting hormone precursor （P-MCH）, ghrelin, and leptin. Results Compared with the OVX control group, the body weight and food intake in the H-S1 group were reduced significantly and there was a significant dose-dependent manner in the 3 isoflavone groups. The results of RT-PCR showed that the NPY level in the 3 isoflavone groups was significantly increased and the POMC/CART gene expression decreased significantly in rats＇ hypothalamus compared with that in the OVX control group. However, the expression of orexin, MCH and P-MCH had no change. The peripheral grelin mRNA expression was higher in the 3 isoflavone groups, while leptin gene expression in the fat was not consistent. Conclusions This research showed that isoflavone could prevent obesity induced by high-fat diet and ovariectomy through regulating hypothalamus and peripheral orexigenic gene expressions associated with food intake.
基金supported by grants from the National Natural Science Foundation of China,No.31171019 and No.31200820the Opening Project of Shanghai Key Laboratory of Brain Functional Genomics and Key Laboratory of Brain Functional Genomics(East China Normal University)of the Ministry of Education
文摘Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere- broventricular dose of metformin and compound C, in a broader attempt to investigate the regula- tory effects of metformin on food intake and to explore the possible mechanism. Results showed that central administration of metformin significantly reduced food intake and body weight gain, par- ticularly after 4 hours. A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase. Furthermore, metformin also improved lipid metabolism by reducing plasma low-density lipoprotein. Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres- sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.
基金supported by a grant from Science and Technical Activities of State Administration of Traditional Chinese Medicine of the People's Republic of China for the Returnees(2005 LHR10)Science and Technical Specialization of State Administration of Traditional Chinese Medicine of the People's Republic of China(06-07 JP54)
文摘Objective:To probe into the most effective site,extra-ordinary point,acupoint and channel for regulating reproductive endocrine function by means of the study on acupuncture activating the gonadotropin-releasing hormone neurons(GnRH) in hypothalamus.Methods:Female SD rats of reproductive age were used,and the in vivo study on GnRH neurons in hypothalamus was made with mimic sexual stimulation and feedback regulation.The neuron-activating effects of the acupoints on the channels pertaining to the zang-and fu-organs related with reproductive endocrine and the extra-ordinary points in different regions were studied using the discharge of the neuron as index,and then the neurons were labeled with horseradish peroxidase(HRP) .Results:Acupuncture was given at two acupoints each on the three yin channels of foot,the three yang channels of foot,the Conception Vessel and the Governor Vessel.The order of the mean increasing percentage in the hypothalamic GnRH neuron electric activity was:the Gallbladder Channel>the Spleen Channel>the Stomach Channel/the Bladder Channel/the Conception Vessel>the Liver Channel>the Kidney Channel>the Governor Vessel;for different acupoints,it was:Guanyuan(CV 4) >Sanyinjiao(SP 6) >Zusanli(ST 36) >Daimai(GB 26) /Yanglingquan(GB 34) >Shenshu(BL 23) >Weizhong(BL 40) >Yaoyangguan(GV 3) /Liangmen(ST 21) /Fujie(SP 14) >Qimen(LR 14) /Yingu(KI 10) >Tangzhong(CV 17) /Zhiyang(GV 9) ;for different positions,it was:the lower abdominal part/the lower limb part>the thoracodorsal part;for the extra-ordinary points,it was:Zigong(EX-CA1) >Dannang(EX-LE6) /Yaoyan(EX-B7) >Baichongwo(EX-LE3) /Qianzheng>Jingbi/Bizhong/Taiyang(EX-HN5) >Erbai(EX-UE2) /Dingchun;and for the distribution sites of the extra-ordinary points:lower abdominal region>the lower limb region>the craniofacial region>the upper limb region/the thoracodorsal region.Conclusion:For regulating the reproductive endocrine function,the acupoints located at the same neural segment with the reproductive organ should be selected as the main points,and it is necessary to combine with syndrome differentiation of the viscera and channels.
基金supported by a grant from National Natural Science Foundation of China(Project No.30800809)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Background： In mammals, leptin is an attractive candidate for mediating the metabolic signal and the reproductive function via the specific receptor in hypothalamus. However, till now, the role of leptin on reproduction in birds is less well established. This experiment was conducted to elucidate the role of leptin on the onset of reproduction in bird, as a first step, to detect the changes of peripheral leptin and leptin receptor mRNA expression in hypothalamus between mature and immature hens at the same age. 120 ISA brown pullets at D60 were allocated randomly into two groups, long light （LL） group being raised under artificial light regimes with incrementally increased light phase （from 8 L：]6D to 14 L：]2D） and short light （SL） group raised on consistent light （8 L：16D） for 12 wk. Results： The results showed that pullets in LL group reached sexual maturation 15 d earlier than those in SL group. Serum E2 showed a significant increase with age, but no difference was observed between two groups. Serum leptin concentration decreased significantly from D112 to D136 in LL, and was markedly higher in LL group than that in SL at D112, while there was no significant difference between two groups at D136. Leptin receptor and GnRH-I mRNA expression in hypothalamus were significantly increased with age, yet there was no significant difference between SL and LL chickens at the same age. The expression of FSH-13 and LH-13 mRNA in pituitary was increased with age but did not show significant difference between LL and gland, and decreased from D112 to D136 in LL but not groups at the same age. SL group. GnfiH-I mRNA expression was very rich in pinea n SL group, and there was no difference between two Conclusions： These results indicate that the earlier sexual maturation in hens induced by long-light regime is not accompanied with an increase in serum leptin or leptin receptor gene expression in hypothalamus, or genes expression in HPG axis.
基金financially supported by National Natural Science Foundation of China(No.30870927)
文摘This study tested the effects of the gastrointestinal pulse train electrical stimulation with different parameters and at different locations on the neuronal activities of the lateral hypothalamus area（LHA） in obese rats in order to find the optimal stimulation parameter and location. Eight gastric electrical stimulations（GES） with different parameters were performed and the neuronal activities of gastric-distension responsive（GD-R） neurons in LHA were observed. The effects of stimulations with 8 parameters were compared to find the optimal parameter. Then the optimal parameter was used to perform electrical stimulation at duodenum and ileum, and the effects of the duodenal and ileac stimulation on the GD-R neurons in LHA were compared with the gastric stimulation of optimal parameter. The results showed that GES with the lowest energy parameter（0.3 ms, 3 mA, 20 Hz, 2 s on, 3 s off） activated the least neurons. The effects of GES with other parameters whose pulse width was 0.3 ms were not significantly different from those of the lowest energy parameter. Most gastric stimulations whose pulse width was 3 ms activated more LHA neurons than the smallest energy parameter stimulation, and the effects of those 3 ms gastric stimulations were similar. Accordingly, the lowest energy parameter was recognized as the optimal parameter. The effects of stimulations with the optimal parameter at stomach, duodenum and ileum on the LHA neuronal activities were not different. Collectively, gastrointestinal electrical stimulation（GIES） with relatively large pulse width might have stronger effects to the neuronal activities of GD-R neurons in LHA of obese rats. The effects of the GIES at different locations（stomach, duodenum and ileum） on those neurons are similar, and GES is preferential because of its easy clinical performance and safety.
文摘There have been fairly good effects ofDecoction Rehmannia(地黄饮子)in treat-ing stroke syndromes.The model of theexperimental cerebral embolism has been es-tablished and the morphological andcytochemical changes of the effect of
基金supported by the National Natural Science Foundation of China (31972638)the National Key Research and Development Program of China (2016YFD0500502)+2 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)the Postgraduate Research&Practice Innovation Program of Jiangsu Province (KYCX18_0716)Jiangsu Collaborative Innovation Center of Meat Production and Processing,Quality,Safety Control
文摘Background:Corticotropin-releasing hormone(CRH),the major secretagogue of the hypothalamic-pituitary-adrenal(HPA)axis,is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions.N6-methyladenosine(m^(6)A)RNA methylation is involved in the regulation of circadian rhythm,yet it remains unknown whether CRH expression and m^(6)A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress.Results:Chronic exposure to corticosterone(CORT)eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken.The circadian rhythms of clock genes in hippocampus,hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens.The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened,together with mRNA of other feeding-related neuropeptides.Interestingly,hypothalamic m^(6)A level oscillates in an opposite pattern to CRH mRNA,with lowestm^(6)A level after midnight(ZT18)corresponding to the peak of CRH mRNA before dawn(ZT22).CORT diminished the circadian rhythm of m^(6)A methylation with significantly increased level at night.Further site-specific m^(6)A analysis on 3’UTR of CRH mRNA indicates that higher m^(6)A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night(ZT18 and ZT22).Conclusions:Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus,leading to dysfunction of HPA axis in the chicken.RNA m^(6)A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions.
文摘In the present study, we reported distribution of ERα and ER β mRNAs in the hypothalamus of young and old ovariectomized （OVX） rhesus macaques. The ERα were detected in all six major vestiblular nuclei which included arcuate nucleus （ARC） , paraventricularis nucleus （PVN） , periventricular nucleus （PeriV） , supraoptic nucleus （SON）, medial prioptic nucleus （MPN） and lateral hypotbalamus area （LHA）. However, the ERβ mRNA can also detected in those nuclei excerpt SON, but the signals of ERβ mRNA were weaker than those of ERα mRNA. We observed that the degree of expression of ERs mRNA were different in most nucleus of old and young monkeys. The ERα mRNAs were highly expressed in ARC and SON in young monkeys compared with old monkeys. Moderate amount of ERα mRNAs hybridization signals and weak signals were observed in LHA, and MPN both in young and old monkeys. In contrast, only lower level of ERα hybridization signal were observed in PVN and PeriV in young monkeys, and the signals of ERα were very low in those nucleus of old monkeys. In general, the expression of ERβ mRNA were weaker than that of ERα mRNA in above nucleus excerpt LHA. The relatively higher density of ERβ hybridization signals have been observed in the LHA in young monkey compared with old monkeys. Low amount of. ERβ mRNA hybridization signals were observed in the ARC, PVN and MPN, and no age differences were seen in PVN and MPN of those monkeys. In PeriV, we observed some signals in young monkey and a few signals in old monkeys. It was different from the rodent in which we did not found ERβ hybridization signal in SON. This study showed that both of the two estrogen receptors not only had the same pattern of expression but also had many different patterns of expression. The different expression of ERα and ERβ mRNAs in the young and old monkey brain may imply diverse functions in different regions of the monkey brain.
基金supported by grants from the National Natural Science Foundation of China (No. 81470150)
文摘Leptin deficiency is principally linked to metabolic disorders. Leptin knockout（Lep△I14/△I14 Sprague Dawley rats created by CRISPR/Cas9 is a new model to study metabolic disorders. We used a whole rat genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of the white adipose tissue, liver and hypothalamus in Lep△I14/△I14）and wild-type（WT） rats. We found 1,651 differentially expressed（enriched） genes in white adipose tissue,916 in the liver, and 306 in the hypothalamus in the Lep△I14/△I14 rats compared to WT. Gene ontology category and KEGG pathway analysis of the relationships among differentially expressed genes showed that these genes were represented in a variety of functional categories, including fatty acid metabolism, molecular transducers and cellular processes. The reliability of the data obtained from microarray was verified by quantitative real-time PCR on 14 representative genes. These data will contribute to a greater understanding of different metabolic disorders, such as obesity and diabetes.
