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ACS Sensors · 2025 · IF 9.1

PtNPs/Prussian Blue-Modified Microelectrode Arrays for Detection of Key Neurons Regulating Hibernation State

Yiding Wang,Chao Yang,Yilin Song,Guihua Xiao,Jiangbei Cao,Weidong Mi,Gucheng Yang,Wei Xu,Yuchuan Dai,Juntao Liu,Zhongquan Dai,Lina Qu,Jinping Luo,Yinghui Li,Xinxia Cai

Studying neuronal activity during hibernation’s extremely low metabolic state may offer novel solutions for metabolic disorders, stroke treatment, and space travel challenges. To explore hibernation’s neural mechanisms, we developed a natural hibernation model using Siberian chipmunks(Tamias sibiricus). However, their characteristic weak neuronal discharge and prolonged hibernation periods necessitate electrodes with both enhanced detection sensitivity and exceptional long-term stability. We developed a new nanocomposite platinum nanoparticles/Prussian blue-modified microelectrode arrays (MEAs) aimed at solving the above difficulties. Prussian blue can react with reactive oxygen species to reduce inflammation during the detection process; therefore, MEAs achieved a high signal-to-noise ratio (15.53 ± 6.73) in the detection of individual neurons, even against weak neural activity in dormant states. We discovered that three types of neurons exhibited distinct responses to hibernation and established three-dimensional characteristics to differentiate them through algorithmic processing of the signal. Type 3 neurons discharged in the extremely low metabolic state, indicating that Type 3 neurons are critical for chipmunks to enter and maintain deep hibernation without damaging the brain. The theta frequency band of local field potentials (LFPs) rapidly increased during arousal, representing consciousness arousal, and can be used as a key signal to predict arousal. These results fill part of the research gaps in the characteristics of critical neurons during hibernation and provide a solid foundation for regulating neurons to control the body into a state of low temperature and low metabolism.

CAS / MDL: 126213-50-1 31175-20-9
研究领域: 神经科学 · 生物医学工程 · 材料科学 · 动物生理学 · 生物电化学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2024 ·Vol. 25 ·期 23 ·12888 · IF 4.9

Involvement of Melatonin, Oxidative Stress, and Inflammation in the Protective Mechanism of the Carotid Artery over the Torpor–Arousal Cycle of Ground Squirrels

Ziwei Hao,Yuting Han,Qi Zhao,Minghui Zhu,Xiaoxuan Liu,Yingyu Yang,Ning An,Dinglin He,Etienne Lefai,Kenneth B. Storey,Hui Chang,Manjiang Xie

Hibernating mammals experience severe hemodynamic changes over the torpor–arousal cycle, with oxygen consumption reaching peaks during the early stage of torpor to re-enter arousal. Melatonin (MT) can improve mitochondrial function and reduce oxidative stress and inflammation. However, the regulatory mechanisms of MT action on the vascular protective function of hibernators are still unclear. Morphology, hemodynamic, mitochondrial oxidative stress, and inflammatory factors of the carotid artery were assessed in ground squirrels who were sampled during summer active (SA), late torpor (LT), and interbout arousal (IBA) conditions. Changes were assessed by methods including hematoxylin and eosin staining, color Doppler ultrasound, ELISA, Western blots, and qPCR. Changes in arterial blood and serum melatonin were also measured by blood gas analyzer and ELISA, whereas mitochondrial oxidative stress and inflammation factors of primary vascular smooth muscle cells (VSMCs) were assessed by qPCR. (1) Intima-media carotid thickness, peak systolic velocity (PSV), end diastolic blood flow velocity (EDV), maximal blood flow rate (Vmax) and pulsatility index (PI) were significantly decreased in the LT group as compared with the SA group, whereas there were no difference between the SA and IBA groups. (2) PO2, oxygen saturation, hematocrit and PCO2in the arterial blood were significantly increased, and pH was significantly decreased in the LT group as compared with the SA and IBA groups. (3) The serum melatonin concentration was significantly increased in the LT group as compared with the SA and IBA groups. (4) MT treatment significantly reduced the elevated levels of LONP1, NF-κB, NLRP3 and IL-6 mRNA expression of VSMCs under hypoxic conditions. (5) Protein expression of HSP60 and LONP1 in the carotid artery were significantly reduced in the LT and IBA groups as compared with the SA group. (6) The proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the carotid artery of the LT group as compared with the SA and IBA groups. The carotid artery experiences no oxidative stress or inflammatory response during the torpor–arousal cycle. In addition, melatonin accumulates during torpor and alleviates oxidative stress and inflammatory responses caused by hypoxia in vitro in VSMCs from ground squirrels.

CAS / MDL: 9002-89-5
研究领域: 生理学 · 分子生物学 · 神经科学 · 心血管研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EXPERIMENTAL PHYSIOLOGY · 2021 ·Vol. 106 ·期 4 ·958-971 · IF 2.969

Differential protein metabolism and regeneration in hypertrophic diaphragm and atrophic gastrocnemius muscles in hibernating Daurian ground squirrels

Xia Yan,Xuli Gao,Qiaohua Niu,Xin Peng,Jie Zhang,Xiufeng Ma,Yanhong Wei,Huiping Wang,Yunfang Gao,Hui Chang

New Findings What is the central question of this study? The aim was to investigate whether diaphragm hypertrophy and gastrocnemius atrophy during hibernation of Daurian ground squirrels involve differential regulation of protein metabolism and regeneration. What is the main finding and its importance? We clarified the differences in protein metabolism and muscle regenerative potential in the diaphragm and gastrocnemius of hibernating ground squirrels, reflecting the different adaptability of muscles. Are differences in the regulation of protein metabolism and regeneration involved in the different phenotypic adaptation mechanisms of muscle hypertrophy and atrophy in hibernators? Two fast-type muscles (diaphragm and gastrocnemius) in summer active and hibernating Daurian ground squirrels were selected to detect changes in cross-sectional area (CSA) and protein expression indicative of protein synthesis metabolism (protein expression of P-Akt, P-mTORC1, P-S6K1 and P-4E-BP1), protein degradation metabolism (MuRF1, atrogin-1, calpain-1, calpain-2, calpastatin, desmin, troponin T, Beclin1 and LC3-II) and muscle regeneration (MyoD, myogenin and myostatin). In the hibernation group compared with the summer active group, the CSA of the diaphragm muscle increased significantly by 26.1%, whereas the CSA of the gastrocnemius muscle decreased significantly by 20.4%. Our study also indicated that increased protein synthesis, decreased protein degradation and increased muscle regenerative potential contributed to diaphragm muscle hypertrophy, whereas decreased protein synthesis, increased protein degradation and decreased muscle regenerative potential contributed to gastrocnemius muscle atrophy. In conclusion, the differences in muscle regeneration and regulatory pattern of protein metabolism might contribute to the different adaptive changes observed in the diaphragm and gastrocnemius muscles of ground squirrels.

CAS / MDL: 115-20-8
研究领域: 生理学 · 生物化学 · 分子生物学 · 动物学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2022 ·Vol. 23 ·期 18 ·10248 · IF 6.208

The Protective Effects on Ischemia–Reperfusion Injury Mechanisms of the Thoracic Aorta in Daurian Ground Squirrels (Spermophilus dauricus) over the Torpor–Arousal Cycle of Hibernation

Yuting Han,Weilan Miao,Ziwei Hao,Ning An,Yingyu Yang,Ziwen Zhang,Jiayu Chen,Kenneth B. Storey,Etienne Lefai,Hui Chang

Hibernators are a natural model of vascular ischemia–reperfusion injury; however, the protective mechanisms involved in dealing with such an injury over the torpor–arousal cycle are unclear. The present study aimed to clarify the changes in the thoracic aorta and serum in summer-active (SA), late-torpor (LT) and interbout-arousal (IBA) Daurian ground squirrels (Spermophilus dauricus). The results show that total antioxidant capacity (TAC) was unchanged, but malondialdehyde (MDA), hydrogen peroxide (H2O2), interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were significantly increased for the LT group, whereas the levels of superoxide dismutase (SOD) and interleukin-10 (IL-10) were significantly reduced in the LT group as compared with the SA group. Moreover, the levels of MDA and IL-1β were significantly reduced, whereas SOD and IL-10 were significantly increased in the IBA group as compared with the SA group. In addition, the lumen area of the thoracic aorta and the expression of the smooth muscle cells (SMCs) contractile marker protein 22α (SM22α) were significantly reduced, whereas the protein expression of the synthetic marker proteins osteopontin (OPN), vimentin (VIM) and proliferating cell nuclear antigen (PCNA) were significantly increased in the LT group as compared with the SA group. Furthermore, the smooth muscle layer of the thoracic aorta was significantly thickened, and PCNA protein expression was significantly reduced in the IBA group as compared with the SA group. The contractile marker proteins SM22α and synthetic marker protein VIM underwent significant localization changes in both LT and IBA groups, with localization of the contractile marker protein α-smooth muscle actin (αSMA) changing only in the IBA group as compared with the SA group. In tunica intima, the serum levels of heparin sulfate (HS) and syndecan-1 (Sy-1) in the LT group were significantly reduced, but the serum level of HS in the IBA group increased significantly as compared with the SA group. Protein expression and localization of endothelial nitric oxide synthase (eNOS) was unchanged in the three groups. In summary, the decrease in reactive oxygen species (ROS) and pro-inflammatory factors and increase in SOD and anti-inflammatory factors during the IBA period induced controlled phenotypic switching of thoracic aortic SMCs and restoration of endothelial permeability to resist ischemic and hypoxic injury during torpor of Daurian ground squirrels.Keywords:torpor–arousal;ischemia–reperfusion;thoracic aortic;phenotypic switching;permeability

CAS / MDL: 9002-89-5
研究领域: 生理学 · 生物化学 · 分子生物学 · 血管生物学
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