TALANTA
·
2025
·
IF 6.1
Jiameng Pei,Lina Tang,Chenyang Kang,Fan Shi,Fengxia Liang,Yutao Li,Guo-Jun Zhang
Acupuncture therapy reduces blood pressure in hypertensive patients by stimulating acupoints located at specific anatomical positions with needles. Hydrogen sulfide (H 2 S) release and accumulation in the paraventricular nucleus (PVN) might be a pivotal step for triggering blood pressure reduction. But to date, the dynamics of H 2 S in the PVN during acupuncture treatment remain unclear. In this work, a multiple-nanomaterial-functionalized microneedle sensor is prepared for real-time monitoring of H 2 S in the PVN of rat while stimulated by electroacupuncture. Gold nanoparticles (AuNPs), molybdenum disulfide (MoS 2 ) and Ag 2 S were sequentially layered on the needle surface. The excellent electrical conductivity of AuNPs, the high carrier mobility of MoS 2 and the high catalytic performance of Ag 2 S ensure sensitive and specific detection of H 2 S in the range of 1 μM–100 μM with detection limit down to 95 nM. The microneedle sensor also demonstrates exceptional stability, remaining effective at room temperature for up to two weeks. Based on this, the microneedle sensor is used to monitor H 2 S release in vivo before and after acupuncture treatment. Our research indicates that acupuncture effectively increases H 2 S levels in the PVN of hypertensive rats, contributing to blood pressure reduction. This microneedle sensor provides a reliable method for monitoring H 2 S release in vivo, offering valuable insights into the role of H 2 S in the neurophysiology of hypertension and the mechanism of acupuncture in its treatment.
研究领域:
神经生理学
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生物传感技术
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中医药学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2017
·Vol. 8
·期 1
·1-15
·
IF 12.124
Wu Liufeng,Meng Jia,Shen Qing,Zhang Yi,Pan Susu,Chen Zhuo,Zhu Ling-Qiang,Lu Youming,Huang Yuan,Zhang Guo
Caffeine, an antagonist of the adenosine receptor A 1 R, is used as a dietary supplement to reduce body weight, although the underlying mechanism is unclear. Here, we report that adenosine level in the cerebrospinal fluid, and hypothalamic expression of A 1 R, are increased in the diet-induced obesity (DIO) mouse. We find that mice with overexpression of A 1 R in the neurons of paraventricular nucleus (PVN) of the hypothalamus are hyperphagic, have glucose intolerance and high body weight. Central or peripheral administration of caffeine reduces the body weight of DIO mice by the suppression of appetite and increasing of energy expenditure. We also show that caffeine excites oxytocin expressing neurons, and blockade of the action of oxytocin significantly attenuates the effect of caffeine on energy balance. These data suggest that caffeine inhibits A 1 Rs expressed on PVN oxytocin neurons to negatively regulate energy balance in DIO mice.
研究领域:
药理学
·
神经科学
·
肥胖研究
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2022
·Vol. 59
·期 11
·7006-7024
·
IF 5.682
Han Chengzhi,Qian Xinyi,Ren Xiaorong,Zhang Shutian,Hu Li,Li Jingyao,Huang Yijun,Huang Renhui,Ooi Kokwin,Lin Hong,Xia Chunmei
Neuroinflammation in the cardiovascular center plays a critical role in the progression of hypertensive heart disease. And microglial autophagy is involved in the regulation of neuroinflammation. Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, senses mitochondrial DNA (mtDNA) and regulates autophagy. The detailed mechanisms of central cGAS affects neuroinflammatory response in hypertensive heart disease via regulating autophagy remain unknown. Angiotensin II (Ang II, 1.5 mg·kg −1 ·12 h −1 , 2 weeks) was intraperitoneally injected to induce hypertension in mice. The cGAS-STING pathway was activated in the paraventricular nucleus (PVN) of Ang II-induced hypertensive mice. The contractile dysfunction of heart was alleviated in Ang II-induced hypertensive cGAS −/− mice. To observe the central effects of cGAS on regulating hypertensive heart disease, the RU.521 (a cGAS inhibitor) was intracisternally infused in hypertensive mice. Intracisternal infusion of the RU.521-alleviated myocardial interstitial fibrosis, cardiomyocyte hypertrophy, and the contractile dysfunction in Ang II-induced hypertensive mice. Intracisternal infusion of RU.521 attenuated the microglial activation, neuroinflammation, sympathetic/parasympathetic activity ratio, and lowered blood pressure. The autophagic flux in the PVN cells was blocked, while intracisternal infusion of RU.521 alleviated this effect in the Ang II-induced hypertensive mice. In vitro, it was found that cGAS-STING activation-induced autophagic flux blockage, while when the impaired autophagic flux was facilitated by rapamycin, an autophagy inducer, the microglial M1 polarization was decreased correspondingly. In conclusion, cGAS induces the inflammatory phenotype of microglia via impairing autophagic flux, thereby participating in neuroinflammation, which leads to sympathetic overactivation in hypertension and further caused hypertensive myocardial injury.
研究领域:
心血管疾病
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神经科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Research
·
2022
·
IF 0
Mo-qiu Jia,Yong-jin Wang,Kang Fu,Han Jiao,Jia Sun,Yuanqing Gao
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.
研究领域:
神经科学
·
内分泌学
·
代谢
✓ 已验证
产品关联
DOI
PubMed
Cell Metabolism
·
2023
·
IF 29
Sijia Fan,Weiwei Guo,Dan Xiao,Mengyuan Guan,Tiepeng Liao,Sufang Peng,Airong Feng,Ziyi Wang,Hao Yin,Min Li,Jue Chen,Wei Xiong
Overeating disorders (ODs), usually stemming from dieting history and stress, remain a pervasive issue in contemporary society, with the pathological mechanisms largely unresolved. Here, we show that alterations in intestinal microbiota are responsible for the excessive intake of palatable foods in OD mice and patients with bulimia nervosa (BN). Stress combined with a history of dieting causes significant changes in the microbiota and the intestinal metabolism, which disinhibit the vagus nerve terminals in the gut and thereby lead to a subsequent hyperactivation of the gut-brain axis passing through the vagus, the solitary tract nucleus, and the paraventricular nucleus of the thalamus. The transplantation of a probiotic Faecalibacterium prausnitzii or dietary supplement of key metabolites restores the activity of the gut-to-brain pathway and thereby alleviates the OD symptoms. Thus, our study delineates how the microbiota-gut-brain axis mediates energy balance, unveils the underlying pathogenesis of the OD, and provides potential therapeutic strategies.
研究领域:
神经科学
·
微生物学
·
营养学
·
精神病学
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产品关联
DOI
PubMed
高影响因子
NEURON
·
2024
·
IF 14.7
Guangjuan Yin,Kaifang Duan,Dong Dong,Feng Du,Chao Guo,Changyi Zhang,Xi Liu,Yuanjie Sun,Tianwen Huang,Guangfu Cui,Longzhen Cheng
Repetitive use of morphine (MF) and other opioids can trigger two major pain-related side effects: opioid-induced hypersensitivity (OIH) and analgesic tolerance, which can be subclassified as mechanical and thermal. The central mechanisms underlying mechanical OIH/tolerance remain unresolved. Here, we report that a brain-to-spinal opioid pathway, starting from μ-opioid receptor (MOR)-expressing neuron in the lateral parabrachial nucleus (lPBN MOR+ ) via dynorphin (Dyn) neuron in the paraventricular hypothalamic nucleus (PVH Dyn+ ) to κ-opioid receptor (KOR)-expressing GABAergic neuron in the spinal dorsal horn (SDH KOR-GABA ), controls repeated systemic administration of MF-induced mechanical OIH and tolerance in mice. The above effect is likely mediated by disruption of dorsal horn gate control for MF-resistant mechanical pain via silencing of the Dyn-positive GABAergic neurons in the SDH (lPBN MOR+ → PVH Dyn+ → SDH KOR-GABA → SDH Dyn-GABA ). Repetitive binding of MF to MORs during repeated MF administration disrupted the above circuits. Targeting the above brain-to-spinal opioid pathways rescued repetitive MF-induced mechanical OIH and tolerance.
研究领域:
神经科学
·
药理学
·
疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNITY
·
2024
·
IF 25.5
Bo Wei,Guo Cheng,Qianqian Bi,Cheng Lu,Qihang Sun,Li Li,Ningting Chen,Miner Hu,Haoran Lu,Xuancheng Xu,Genxiang Mao,Shu Wan,Zhechun Hu,Yan Gu,Jiaxin Zheng,Li Zhao,Xiao Z. Shen,Xiaoli Liu,Peng Shi
Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y12 receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.
研究领域:
神经科学
·
心血管研究
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL
·
2023
·
IF 64.5
Jian-Jun Meng,Jia-Wei Shen,Guang Li,Chang-Jie Ouyang,Jia-Xi Hu,Zi-Shuo Li,Hang Zhao,Yi-Ming Shi,Mei Zhang,Rong Liu,Ju-Tao Chen,Yu-Qian Ma,Huan Zhao,Tian Xue
Summary Public health studies indicate that artificial light is a high-risk factor for metabolic disorders . However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus , and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism , which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.
研究领域:
神经科学
·
代谢学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2022
·
IF 4.114
Hongzeng Li,Wen Yuan,Yuxin Tian,Feiyue Tian,Yunfei Wang,Xiangrong Sun,Yanling Gong
Eugenol, an active ingredient of many medicinal aromatic plants, has been proved to have the hypolipidemic effect, but its potential mechanism of action is still unknown. This study aimed to investigate whether eugenol regulates liver lipid accumulation in high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD) rats via the gut-brain-liver axis involving glucagon-like peptide-1 (GLP-1). Hepatic vagotomy was performed in NAFLD rats to determine the role of eugenol in regulating hepatic lipid accumulation via vagus nerve. The results showed that after eight weeks of eugenol administration in NAFLD rats, serum total cholesterol (TC), triglyceride (TG) and hepatic TG decreased. However, eugenol showed no significant effect on the increased food intakes and weight gain caused by the HFD. Eugenol promoted the secretion of GLP-1 into the blood, increased GLP-1 receptor (GLP-1R) expression in the duodenum , liver, arcuate nucleus (ARC) and paraventricular nucleus (PVN), increased c-fos expression in the nucleus tractus solitarii (NTS), and promoted ZO-1 and occludin expression in duodenum. Furthermore, steatosis and lipid accumulation were significantly alleviated. Hepatic vagotomy partially attenuated the improvement of eugenol in hepatic lipid accumulation in NAFLD rats. In conclusion, eugenol regulates hepatic lipid metabolism via a gut-brain-liver axis involving in GLP-1, providing a new strategy for the treatment of NAFLD.
研究领域:
药理学
·
肝病学
·
内分泌学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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