Nature Communications
·
2024
·Vol. 15
·期 1
·1-18
·
IF 14.7
Zhang Yan,Shen Jiayi,Xie Famin,Liu Zhiwei,Yin Fangfang,Cheng Mingxiu,Wang Liang,Cai Meiting,Herzog Herbert,Wu Ping,Zhang Zhi,Zhan Cheng,Liu Tiemin
Resistance to stress is a key determinant for mammalian functioning. While many studies have revealed neural circuits and substrates responsible for initiating and mediating stress responses, little is known about how the brain resists to stress and prevents overreactions. Here, we identified a previously uncharacterized neuropeptide Y (NPY) neuronal population in the dorsal raphe nucleus and ventrolateral periaqueductal gray region (DRN/vlPAG) with anxiolytic effects in male mice. NPY DRN/vlPAG neurons are rapidly activated by various stressful stimuli. Inhibiting these neurons exacerbated hypophagic and anxiety responses during stress, while activation significantly ameliorates acute stress-induced hypophagia and anxiety levels and transmits positive valence. Furthermore, NPY DRN/vlPAG neurons exert differential but synergic anxiolytic effects via inhibitory projections to the paraventricular thalamic nucleus (PVT) and the lateral hypothalamic area (LH). Together, our findings reveal a feedforward inhibition neural mechanism underlying stress resistance and suggest NPY DRN/vlPAG neurons as a potential therapeutic target for stress-related disorders.
研究领域:
神经科学
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应激生物学
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行为神经科学
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DOI
PubMed
高影响因子
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2025
·
IF 8.4
Zhang Jia-qi,Li Shu-yi,Yin Cui,Ji Ying,Zhang Xiang,Liu Dan-yang,Yang Hang,Niu Yong,Cui Gui-yun,Zhou Chun-yi,Xiao Cheng
Anxiety and depression are common non-motor symptoms severely affecting the quality of life in patients with Parkinson’s disease, but the underlying pathophysiological mechanisms remain elusive. As dopaminergic (DA) system and the subthalamic nucleus (STN) are involved in motor control and emotional processing, we herein investigated the role of DA circuitry in the STN in regulating depression in parkinsonian mice. A hemi-parkinsonian mouse model was established by injection of 6-OHDA into the right medial forebrain bundle (MFB), desipramine (20 mg/kg, i.p.) was injected 30 min before the intracranial injection. Motor function was monitored in open field test and apomorphine-induced contra-lesional rotation and rotarod tests; anxiety- and depression-like behaviors were assessed with the open field test, elevated plus maze, tail suspension test and forced swim test. We found that the hemi-parkinsonian mice displayed motor dysfunction and depression-like behaviors at different time points. Fiber photometry recording revealed that STN neurons were hypersensitive to anxiety- and depression-like stimulation; chemogenetic inhibition of STN neurons mitigated anxiety- and depression-like behaviors. While dopamine release was significantly reduced in the STN of the parkinsonian mice in response to anxiety- and depression-like stimulation, the expression of D1- and D2-like dopamine receptors was time-dependently changed. Intracranial injection of either D1- or D2-like dopamine receptor agonist into the STN mitigated anxiety- and depression-like behaviors in the parkinsonian mice. We conclude that STN DA circuitry may be promising targets to treat anxiety and depression in PD.
研究领域:
神经科学
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药理学
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行为学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Neuroscience
·
2023
·
IF 4.3
Xue Tao,Wang Shu,Chen Shujun,Wang Huizhi,Liu Chong,Shi Lin,Bai Yutong,Zhang Chunkui,Han Chunlei,Zhang Jianguo
Background: Focal motor seizures that originate in the motor region are a considerable challenge because of the high risk of permanent motor deficits after resection. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a potential treatment for motor epilepsy that may enhance the antiepileptic actions of the substantia nigra pars reticulata (SNr). Orexin and its receptors have a relationship with both STN-DBS and epilepsy. We aimed to investigate whether and how STN inputs to the SNr regulate seizures and the role of the orexin pathway in this process.Methods: A penicillin-induced motor epileptic model in adult male C57BL/6 J mice was established to evaluate the efficacy of STN-DBS in modulating seizure activities. Optogenetic and chemogenetic approaches were employed to regulate STN-SNr circuits. Selective orexin receptor type 1 and 2 antagonists were used to inhibit the orexin pathway.Results: First, we found that high-frequency ipsilateral or bilateral STN-DBS was effective in reducing seizure activity in the penicillin-induced motor epilepsy model. Second, inhibition of STN excitatory neurons and STN-SNr projections alleviates seizure activities, whereas their activation amplifies seizure activities. In addition, activation of the STN-SNr circuits also reversed the protective effect of STN-DBS on motor epilepsy. Finally, we observed that STN-DBS reduced the elevated expression of orexin and its receptors in the SNr during seizures and that using a combination of selective orexin receptor antagonists also reduced seizure activity.Conclusion: STN-DBS helps reduce motor seizure activity by inhibiting the STN-SNr circuit. Additionally, orexin receptor antagonists show potential in suppressing motor seizure activity and may be a promising therapeutic option in the future.
研究领域:
神经科学
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医学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
IN VIVO
·
2024
·Vol. 38
·期 3
·1133-1142
·
IF 1.8
LONGJIE XU,LILI HOU,CHUN CAO,XIAOHUA LI
Background/Aim: Cancer-induced bone pain (CIBP) is one of the most common symptoms of bone metastasis of tumor cells. The hypothalamus may play a pivotal role in the regulation of CIBP. However, little is known about the exact mechanisms. Materials and Methods: First, we established a CIBP model to explore the relationship among hypothalamic ghrelin, NPY and CIBP. Then, we exogenously administered NPY and NPY receptor antagonists to investigate whether hypothalamic NPY exerted an antinociceptive effect through binding to NPY receptors. Finally, we exogenously administered ghrelin to investigate whether ghrelin alleviated CIBP by inducing the production of hypothalamic NPY through the AMPK-mTOR pathway. Body weight, food intake and behavioral indicators of CIBP were measured every 3 days. Hypothalamic ghrelin, NPY and the AMPK-mTOR pathway were also measured. Results: The expression of hypothalamic ghrelin and NPY was simultaneously decreased in cancer-bearing rats, which was accompanied by CIBP. Intracerebroventricular (i.c.v.) administration of NPY significantly alleviated CIBP in the short term. The antinociceptive effect of NPY was reversed with the i.c.v. administration of the Y1R and Y2R antagonists. The administration of ghrelin activated the AMPK-mTOR pathway and induced hypothalamic NPY production to alleviate CIBP. This effect of ghrelin on NPY and antinociception was reversed with the administration of a GHS-R1α antagonist. Conclusion: Ghrelin could induce the production of hypothalamic NPY through the AMPK-mTOR pathway to alleviate CIBP, which can provide a novel therapeutic mechanism for CIBP.
研究领域:
神经科学
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疼痛研究
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肿瘤学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
PLOS BIOLOGY
·
2025
·Vol. 23
·期 5
·e3003170
·
IF 7.2
Shu-Ting Bao,Fang Rao,Cui Yin,Yong Niu,Jun-Li Cao,Cheng Xiao,Chunyi Zhou
The medial prefrontal cortex (mPFC) is implicated in emotional processing, cognition, and pain sensation, moreover, its circuitry undergoes neuroplastic changes in chronic pain. Although the nucleus reuniens (RE) of the thalamus provides significant glutamatergic inputs to the mPFC, it remains unclear whether this projection contributes to plasticity changes in the mPFC and pain-related behaviors in chronic pain. Using fiber photometry, we demonstrated that RE neurons responded to pain stimulation and emotional changes. Optogenetic activation of RE neurons and their projections to the mPFC (RE-mPFC projection) elicits hyperalgesia and depression-like behaviors in naïve mice. In a neuropathic pain mouse model, RE neurons were hyperactive, and the RE-mPFC projection was enhanced with a marked preference for the part innervating GABAergic circuits in the mPFC to that controlling mPFC neurons projecting to the ventrolateral periaqueductal gray (vlPAG). Expectedly, optogenetic inhibition of RE neurons and the RE-mPFC projection ameliorated pain-like and depression-like behaviors in neuropathic pain mice. Additionally, chemogenetic inhibition of RE-mPFC neurons conferred analgesia in neuropathic pain mice exposed to both acute and chronic morphine. Our findings highlight the significant role of the RE-mPFC pathway in neuropathic pain comorbid with depression, suggesting its potential as a target for treatment of neuropathic pain.
研究领域:
神经科学
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疼痛研究
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行为学
✓ 已验证
DOI
PubMed
高影响因子
NEURON
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2022
·
IF 18.688
Yu-Ting Tseng,Binghao Zhao,Shanping Chen,Jialin Ye,Jingjing Liu,Lisha Liang,Hui Ding,Bernhard Schaefke,Qin Yang,Lina Wang,Feng Wang,Liping Wang
Summary When an animal faces a threatening situation while asleep, rapid arousal is the essential prerequisite for an adequate response. Here, we find that predator stimuli induce immediate arousal from REM sleep compared with NREM sleep. Using in vivo neural activity recording and cell-type-specific manipulations, we identify neurons in the medial subthalamic nucleus (mSTN) expressing corticotropin-releasing hormone (CRH) that mediate arousal and defensive responses to acute predator threats received through multiple sensory modalities across REM sleep and wakefulness. We observe involvement of the same neurons in the normal regulation of REM sleep and the adaptive increase in REM sleep induced by sustained predator stress. Projections to the lateral globus pallidus (LGP) are the effector pathway for the threat-coping responses and REM-sleep expression. Together, our findings suggest adaptive REM-sleep responses could be protective against threats and uncover a critical component of the neural circuitry at their basis.
研究领域:
神经科学
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睡眠研究
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行为神经科学
✓ 已验证
DOI
PubMed
高影响因子
CELL RESEARCH
·
2025
·
IF 25.9
Xie Ling-Qi,Hu Biao,Lu Ren-Bin,Cheng Ya-Lun,Chen Xin,Wen Jie,Xiao Yao,An Yu-Ze,Peng Ning,Dai Yu,Xie Genqing,Guo Qi,Peng Hui,Luo Xiang-Hang
Sleep deficiency is associated with obesity, but the mechanisms underlying this connection remain unclear. Here, we identify a sleep-inducible hypothalamic protein hormone in humans and mice that suppresses obesity. This hormone is cleaved from reticulocalbin-2 (RCN2), and we name it Raptin. Raptin release is timed by the circuit from vasopressin-expressing neurons in the suprachiasmatic nucleus to RCN2-positive neurons in the paraventricular nucleus. Raptin levels peak during sleep, which is blunted by sleep deficiency. Raptin binds to glutamate metabotropic receptor 3 (GRM3) in neurons of the hypothalamus and stomach to inhibit appetite and gastric emptying, respectively. Raptin-GRM3 signaling mediates anorexigenic effects via PI3K-AKT signaling. Of note, we verify the connections between deficiencies in the sleeping state, impaired Raptin release, and obesity in patients with sleep deficiency. Moreover, humans carrying an RCN2 nonsense variant present with night eating syndrome and obesity. These data define a unique hormone that suppresses food intake and prevents obesity.
研究领域:
神经科学
·
内分泌学
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代谢研究
·
睡眠医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Integrative Neuroscience
·
2024
·Vol. 23
·期 11
·208
·
IF 2.5
Xiaoli Dai,Yuanyuan He,Xinghui Han,Wen Sun,Jian Yu,Yating Lin,Yonghong Wang
Background: The insulin-like growth factor (IGF) system plays a vital role in regulating gonadotropin-releasing hormone (GnRH), whether the IGF2 can act on the GnRH neurons during the pubertal period is unclear.
Methods: Central precocious puberty (CPP) rats were induced by danazol, and when the rats met the first diestrus, they were euthanized and tissues were collected. GT1-7 cells were cultured and treated with 0, 1, 10 ng/mL IGF2 for 4 hours and the changes in GnRH were measured. Mice were injected intracerebroventricularly with IGF2 (15 ng/g, 5 μL) or with the same dose of phosphate buffered saline (PBS), after eight hours, they were euthanized and tissues collected.
Results: CPP rats had increased expression of IGF2 and GnRH mRNA and their respective proteins in the preoptic area (POA) of the hypothalamus. Treatment of GT1-7 cells with 10 ng/mL of IGF2 increased GnRH mRNA and protein expression, and GnRH concentration in the culture medium. Injection of IGF2 protein into the lateral ventricle of mice increased the expression of GnRH mRNA and protein in the POA. Conclusions: IGF2 may upregulate the synthesis of GnRH during the pubertal period, and may also take part in the pathology of CPP.
研究领域:
内分泌学
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生殖生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Energy
·
2021
·
IF 17.881
Guangyou Yang,Yong Tang,Tao Lin,Tianyan Zhong,Yaowei Fan,Yan Zhang,Lili Xing,Xinyu Xue,Yang Zhan
The traditional methods of detecting and adjusting blood glucose concentration, such as blood analysis and insulin injection, may delay the treatment of metabolic disease . Here, a new self-powered closed-loop brain-machine-interface system for real-time detecting and rapidly adjusting blood glucose concentration has been fabricated. The system can work without external power supply and be self-powered by the body motion itself, which can meet the requirement of immediate treatment. The system mainly consists of active blood glucose sensor, energy harvester , micro-control unit and brain stimulator . The blood glucose sensor made of enzyme/ZnO nanowire arrays can output piezoelectric voltage under the driving of body motion, and the output can be treated as the glucose-detecting signal through the biosensing-piezoelectric coupling effect. A piezoelectric ceramic device as the energy harvester can convert the body mechanical energy into electricity for powering the whole system. The micro-control unit outputs brain stimulation pulse to the dorsomedial part of the ventromedial hypothalamus (VMHdm) in the brain upon abnormal blood glucose concentration . In mouse samples, the brain stimulator connected to the VMHdm augments the expression of regulatory nerve receptors to achieve rapid increase of blood glucose concentration (39% within 10 min). Thus, a closed loop is formed among the body, brain and system. This self-powered closed-loop approach improves the accessibility of physiological insights and extends brain-machine-interface application in precision medicine for metabolic diseases.
研究领域:
生物医学工程
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代谢病学
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神经工程
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转化医学
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糖尿病研究
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分子传感
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可穿戴设备
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Xiaoqing Shen,Jing Lian,Chao Zhang,Yixiang Miu,Yuan Zhang,Ji Shi,Nan Xu,Tianzhu Jia
Introduction: Kidney Yang Deficiency (KYD) is a metabolic disorder associated with kidney damage. Its slow progression means that causative factors and effective therapeutic agents remain unclear. Extensive evidence links KYD to gut microbiome metabolic diseases and the Hypothalamic-Pituitary-Thyroid (HPT) axis. Cistanche deserticola (CD) is a commonly used traditional Chinese medicine for treating KYD. However, the precise interactions between gut microbiota and KYD, as well as the mechanisms of raw and processed CD total glycosides (CDG) in modulating KYD, require further investigation. This study aims to evaluate the effects and mechanisms of CDG in a KYD rat model using 16S rRNA gene sequencing and fecal metabolomics.Methods: CDG was extracted from both raw and processed CD and analyzed via HPLC. Propylthiouracil-induced KYD rats were used to assess pharmacological effects, including serum levels of T3, T4, TSH, TRH, FFA, LPL, and NO; organ indices of the spleen, kidney, and thymus; blood cAMP/cGMP levels; and liver levels of glycogen, SDH, Ca2+-ATPase, and Na+-K+-ATPase. Immunohistochemistry was also performed.Results: Fecal non-targeted metabolomics identified 98 metabolites associated with KYD, while 16S rRNA sequencing revealed 13 key intestinal microbiotas linked to KYD. CDG therapy effectively alleviated KYD symptoms by modulating the gut microbiota, improving metabolic and microbial imbalances in KYD. RG/WG significantly improves KYD rats mainly through the relationship between the intestinal microbiota and arachidonic acid metabolism. The key bacterial genera lleibacterium and Streptococcus observed in the changes of intestinal flora and fecal metabolite content were significantly negatively correlated with phosphatidylcholine and phosphatidylethanolamine.Discussion: This integrative approach of gut microbiome and fecal metabolomics not only provides a scientific basis for CDG’s preventive effects on KYD via the HPT axis but also elucidates the potential mechanisms underlying CDG’s action against KYD.
研究领域:
中医药学
·
药理学
·
微生物学
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分子生物学
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代谢组学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Xu Xiang-Ying,Xiao Yue,Liu Xu,Huang Yue,Ji Ying,Ji Yawei,Gao Yuan,Liu Su,Yang Jian-Jun,Cao Jun-Li,Zhou Chunyi,Xiao Cheng
Much progress has been made in the understanding of the neural circuits associated with sleep and anesthesia. As an important component among these circuits, the forebrain nuclei have been frequently interrogated. This study demonstrates that glutamatergic (Glu) neurons in the ventral pallidum (VP) enhance activity upon salient stimuli and state-dependently modulate brain arousal and motor activity in freely behaving male mice, and bidirectionally regulate the induction of and emergence from isoflurane general anesthesia. We delineate a neural pathway, consisting of VP Glu neurons→ noradrenergic (NA) neurons in the locus coeruleus (LC)→the lateral hypothalamus (LH) in male mice, controlling the release of noradrenaline in the LH and state-dependently modulated brain arousal, motor activity, and isoflurane general anesthesia through α2a receptors in the LH. Therefore, the VP Glu -LC NA -LH pathway and α2a receptors in the LH may be promising state-dependent regulators of brain arousal in both freely behaving and anesthetized states.
研究领域:
神经科学
·
麻醉学
·
行为学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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