Journal of physiological investigation最新文献

{"title":"Structural and Functional Changes of the Heart in Young Adult Tennis Players.","authors":"Hsu-Chun Huang, Wei-Ting Lin, Ruei-Shyang Liu, I-Wei Lu, Chia-Chin Chiang, Hsiang-Chun Lee","doi":"10.4103/ejpi.EJPI-D-24-00106","DOIUrl":"10.4103/ejpi.EJPI-D-24-00106","url":null,"abstract":"<p><strong>Abstract: </strong>This cross-sectional observational study investigated undetermined cardiac remodeling and functional adaptation in young tennis players. Fourteen males with regular tennis training (at least three times a week, mean playing age 8.3 ± 3.8 years, tennis group, tennis) and 12 males without any racket sports engagement (the control group, [CTL]) underwent comprehensive cardiac measurements using real-time three-dimensional echocardiography, recording of baseline characteristics, blood tests, and estimation of VO 2 max by 12-min running. Data were analyzed to compare the two groups. Two groups were of similar age (mean age, CTL 20.9 ± 2.4 vs. tennis 22.5 ± 4.4 years, P = 0.235) and with similar body size. Compared with the CTL, Tennis group had slower pulse rate (70.9 ± 7.0/min vs. CTL 85.5 ± 9.6/min, P < 0.001), greater VO 2 max (43.4 ± 3.8 mL/Kg/min vs. CTL 33.1 ± 4.8 mL/Kg/min, P < 0.001), but similar blood levels of hematocrit, NT-pro-brain natriuretic peptide, and creatinine phosphokinase. The tennis group had greater left ventricle posterior wall thickness (0.90 ± 0.06 cm vs. CTL 0.81 ± 0.10 cm, P < 0.001), greater right ventricle (RV) volume index (77.8 ± 9.6 mL vs. CTL 64.9 ± 10.1 mL, P = 0.003), and greater left atrial volume index (26.9 ± 5.5 mL/m 2 vs. CTL 21.9 ± 2.7 mL/m 2 , P = 0.006). The tennis group had significantly increased RV strain (free wall strain, -26.5 ± 3.7% vs. CTL -23.3 ±2.8%, P = 0.025). However, the global longitudinal strains in the left atrium and left ventricle were similar between the two groups. Cardiac remodeling in young tennis players includes right ventricular dilatation with enhanced dynamic function, an enlarged left atrium with well-preserved function, and a predominant posterior wall thickening of the left ventricle.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"150-157"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Transchalcone on Neurological Outcomes in Cerebral Ischemia-reperfusion Injury in Rat: Role of AMP-activated Protein Kinase-mitochondrial Signaling Pathways.","authors":"Xiuyun Xue, Jingjing Du, Shaik Althaf Hussain, Narendra Maddu, Jing Xiong","doi":"10.4103/ejpi.EJPI-D-25-00004","DOIUrl":"10.4103/ejpi.EJPI-D-25-00004","url":null,"abstract":"<p><strong>Abstract: </strong>Cerebral ischemia-reperfusion (CIR) injury results in significant secondary brain damage after ischemic stroke due to oxidative stress, mitochondrial dysfunction, and neuroinflammation. Transchalcone (TCH), a polyphenolic compound, exhibits antioxidant and anti-inflammatory properties that may contribute to neuroprotection. The present study investigated the potential protective effects of TCH in a rat model of CIR, focusing on its impact on the activation of AMP-activated protein kinase (AMPK) pathway, mitochondrial function, and inflammatory mediators. Sixty adult Sprague-Dawley rats were randomly divided into five groups of Control, CIR (ischemia-reperfusion only), CIR+TCH (CIR with TCH), CIR+CC (CIR with compound C), and CIR+CC+TCH (CIR with compound C plus TCH). TCH (100 μg/kg b.w per day) was given intraperitoneally over 7 days before CIR injury to animals. Middle cerebral artery occlusion was performed for 60 min to induce cerebral ischemia, and then blood flow was restored (reperfusion) for 24 h. Neuromotor function was assessed using neurological scoring, rotarod, and grid tests. The infarct volumes were determined using 2,3,5-triphenyltetrazolium chloride staining. Mitochondrial function was evaluated using fluorometric and calorimetric methods. Oxidative stress and inflammatory mediators were measured by enzyme-linked immunosorbent assay. Protein expression was analyzed using Western blotting. CIR significantly impaired neuromotor function, increased infarct volume, elevated mitochondrial reactive oxygen species (ROS) levels, and disrupted adenosine triphosphate (ATP) synthesis and manganese superoxide dismutase (Mn-SOD) activity. It also heightened pro-inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-alpha, and nuclear factor kappa B levels while reducing the anti-inflammatory IL-10 level. TCH treatment significantly attenuated CIR outcomes by promoting AMPK phosphorylation, upregulating peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and nuclear factor erythroid 2-related factor 2 (NRF2) expression, reducing mitochondrial ROS, improving ATP production and Mn-SOD activity, and suppressing pro-inflammatory cytokine mediators while increasing IL-10. Co-treatment with compound C (a selective AMPK inhibitor) significantly diminished the protective effects of TCH, confirming the contribution of AMPK signaling in its neuroprotective mechanism. TCH provides significant neuroprotection against CIR injury by activating AMPK/PGC-1α and AMPK/NRF2 signaling, preserving mitochondrial function, and modulating inflammation. These findings highlight the therapeutic potential of TCH for ischemic stroke management.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"168-175"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-367-3p Alleviates Oxidative Stress Injury in the Ischemia/Reperfusion Injury Cell Model by Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4-mediated Keap1/Nrf2/ARE Pathway.","authors":"Qian He, Xingwen Tian, Yujie Zhang, Qiong Mu","doi":"10.4103/ejpi.EJPI-D-24-00103","DOIUrl":"10.4103/ejpi.EJPI-D-24-00103","url":null,"abstract":"<p><strong>Abstract: </strong>Ischemic stroke is a debilitating central nervous disease linked to oxidative stress. Although miR-367-3p has been reported to be related to ischemic stroke, the direct evidence concerning oxidative stress remains elusive. Our study aimed to elucidate the mechanisms associated with oxidative stress in ischemic stroke. Initially, we discovered that miR-367-3p was notably downregulated in SH-SY5Y cells induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Employing the in vitro ischemia/reperfusion injury model, we further demonstrated that overexpression of miR-367-3p alleviated OGD/R-induced apoptosis, inflammation, and oxidative stress, accompanied by the activation of the Keap1/Nrf2/ARE pathway. Mechanistically, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) was confirmed to be the target of miR-367-3p by dual-luciferase reporter assay. Moreover, the knockdown of NOX4 mimicked, while overexpression reversed the effects of miR-367-3p overexpression on OGD/R-induced oxidative stress injury and the impaired Keap1/Nrf2/ARE pathway. In conclusion, our findings indicate that miR-367-3p mitigates OGD/R-induced oxidative stress injury by activating the Keap1/Nrf2/ARE pathway through targeting NOX4.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"140-149"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Action of Exercise in Regulating Spontaneous Hypertension through the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling Pathway.","authors":"Yu Li, Xiaoju Song, Lianjing Dai, Yangyi Wang, Qiong Luo, Lei Lei, Yunfei Pu","doi":"10.4103/ejpi.EJPI-D-24-00085","DOIUrl":"10.4103/ejpi.EJPI-D-24-00085","url":null,"abstract":"<p><strong>Abstract: </strong>Although blood pressure can be regulated to normal levels through drug intervention, the prognosis for patients remains bleak, and there is an urgent need to find a new way to prevent or reverse hypertension and its adverse consequences. Some studies have shown that hypertension can be effectively improved by exercise training, but the exact manner in which it works is not completely comprehended. Using spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats as models, an 8-week exercise intervention was adopted to detect the blood pressure, heart rate (HR), glucose tolerance, and insulin sensitivity. Histopathological changes in rat myocardium were observed using H and E staining and Masson staining. Different kits were used to detect the inflammation and oxidative stress in rats. Finally, the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway-related proteins were examined by Western blot. After exercise, SHR rats showed a decrease in blood pressure and HR level, and an increase in glucose tolerance and myocardial insulin sensitivity. Exercise reduced SHR cardiomyocyte cross-sectional area and collagen deposition index, improved cardiac function, and decreased inflammation and oxidative stress. In addition, exercise can modulate the JAK2/STAT3 pathway, and when combined with JAK2 kinase inhibitor, it has an even greater effect on SHR. In conclusion, exercise could reduce blood pressure, inflammation, and oxidative stress, improve glucose tolerance and insulin sensitivity in SHR rats through modulating the JAK2/STAT3 pathway.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"109-119"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-455-5p Mitigates Interleukin-1 β-induced Chondrocyte Damage Linked to Osteoarthritis by Targeting TNFAIP8.","authors":"Tao Zhang, Wei Wang, Jinlei Sun, Long Luo, Yuan Li, Zhixiong Xu, Wensheng Xu","doi":"10.4103/ejpi.EJPI-D-24-00102","DOIUrl":"10.4103/ejpi.EJPI-D-24-00102","url":null,"abstract":"<p><strong>Abstract: </strong>MicroRNAs have been extensively implicated in osteoarthritis (OA) progression. Our study aims to investigate the impact of miR-455-5p on OA progression and related molecular mechanisms. Cartilage tissues were collected from patients with OA and femoral neck fractures. An in vitro OA model was established by inducing injury in human chondrocytes (CHON-001) with interleukin (IL)-1 β. Cell viability and apoptosis were measured by cell counting kit-8 and flow cytometry assays, respectively. An enzyme-linked immunosorbent assay was performed to measure the concentrations of inflammation factors, and oxidative stress was evaluated by detecting superoxide dismutase activity and malondialdehyde levels. TargetScan was used to predict the binding sites between miR-455-5p and tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8), which were then confirmed by dual-luciferase reporter assays. Quantitative real-time polymerase chain reaction and western blot analysis were employed to measure the related molecular markers. Our initial observations showed that the expression of miR-455-5p was downregulated in OA cartilage and IL-1 β-treated CHON-001 cells compared to normal cartilage tissues and untreated cells. Overexpression of miR-455-5p significantly protected CHON-001 cells from IL-1 β-induced injury by recovering cell viability, and inhibiting inflammation, apoptosis, and oxidative stress. TNFAIP8 was targeted by miR-455-5p and negatively regulated by miR-455-5p. TNFAIP8 knockdown imitated, while overexpression reversed the effects mediated by miR-455-5p in IL-1 β-induced chondrocyte injury, as further confirmed by the protein levels of iNOS, cleaved caspase-3, NQO1, Col2a1, and MMP13. Collectively, these results suggest that miR-455-5p may serve as a new therapeutic target for OA by targeting TNFAIP8 to alleviate IL-1 β-induced chondrocyte injury.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"100-108"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen Sulfide Inhibits Ferritinophagy-Mediated Ferroptosis in the Hippocampus of Rotenone-Exposed Rats.","authors":"Xi Chen, Li Liu, Wu Jiang, Yu Hu, Wei Zou, Ping Zhang, Bo Wang","doi":"10.4103/ejpi.EJPI-D-24-00099","DOIUrl":"10.4103/ejpi.EJPI-D-24-00099","url":null,"abstract":"<p><strong>Abstract: </strong>Our previous research has established that hydrogen sulfide (H 2 S) exerts an antagonistic effect against the hippocampal neurotoxicity induced by Rotenone (ROT). However, the underlying mechanisms are so far poorly understood. Substantial evidence corroborates the involvement of ferroptosis in ROT-induced neurotoxicity. To elucidate the protective mechanism of H 2 S against ROT-induced hippocampal neurotoxicity, this study explores its regulatory role in ferroptosis and its underlying mechanisms. We used Fluoro-Jade B staining to detect dead neurons. The levels of ferrous ions and glutathione (GSH) were measured by a kit. The ferroptosis-related proteins, including light-chain subunit (xCT), GSH peroxidase 4(GPX4), ferroptosis marker acyl-CoA synthetase long-chain family member 4(ACSL4), and ferritinophagy-related protein, including ferritin heavy chain 1 (FTH1), sequestosome 1 (p62), ferritinophagy markers autophagosome marker light-chain I/II (LC3I/II), and nuclear receptor coactivator 4 (NCOA4), were measured by Western blot. Our findings indicate that H 2 S reduces hippocampal neuron deaths in ROT-exposed rats. Meanwhile, H 2 S reverses the downregulations of xCT and GPX4, and the upregulations of ferrous ion and ACSL4 in the hippocampus induced by ROT. Furthermore, H 2 S reverses the upregulations of LC3I/II and NCOA4, and the downregulations of P62 and FTH1. Based on these findings, we concluded that the protective role of H 2 S against ROT-induced hippocampal neuronal death involves inhibiting ferroptosis triggered by ferritinophagy.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"91-99"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Posttraining Dry Cupping Treatment Elevates Heart Rate Variability in Taekwondo Athletes.","authors":"Chi-Cheng Lu, Bao-Lien Hung, Ai-Chi Zheng, Yi-Ying Chen, Shih-Hua Fang","doi":"10.4103/ejpi.EJPI-D-24-00087","DOIUrl":"10.4103/ejpi.EJPI-D-24-00087","url":null,"abstract":"<p><strong>Abstract: </strong>Elite taekwondo (TKD) athletes require physical strength and mastery of complex techniques to excel in a highly competitive environment. This study aimed to investigate the effects of dry cupping posttraining on heart rate variability (HRV) and recovery in TKD athletes. Fourteen male TKD athletes participated in a crossover study and were randomly assigned to either a dry cupping (Group CUP) or a placebo group without cupping (Group PLA) after completing a standardized TKD-specific training program. A 28-day washout period was implemented between the two treatments to minimize potential carryover effects. HRV and rated perceived exertion (RPE) were evaluated at three-time points: before training (Pre), immediately after training (Post), and 30 min after rest or dry cupping (Post30) in both groups. The results indicated that heart rate (HR) at Post and Post30 was significantly higher than at Pre in both groups. Low frequency (LF) and the LF/high frequency (HF) ratio at Post were significantly elevated compared to Pre in both groups. However, at Post30, these values remained significantly higher in Group PLA but not in Group CUP. HF at Post was significantly reduced compared to Pre in both groups, but at Post30, this reduction persisted only in Group PLA and not in Group CUP. Significant differences in the levels of LF, HF, and the LF/HF ratio were observed between Group PLA and Group CUP at Post30. The CUP group also showed significantly lower RPE compared to the PLA group at Post30. In conclusion, dry cupping treatment after TKD training significantly improved HRV parameters and reduced perceived fatigue, suggesting its potential as an effective method for enhancing recovery in TKD athletes.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"84-90"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Acupuncture of 13 Ghost Points Combined with Cognitive Therapy in Alleviating Liver-qi Stagnation Depression: A Clinical Study.","authors":"Xiaojian Yin, Xianyong Wang","doi":"10.4103/ejpi.EJPI-D-24-00064","DOIUrl":"10.4103/ejpi.EJPI-D-24-00064","url":null,"abstract":"<p><strong>Abstract: </strong>Liver-qi stagnation-type depression, marked by irritability and emotional imbalance, often responds inadequately to medication alone. This study explored the efficacy of combining acupuncture at the 13 ghost points with cognitive therapy for this condition. Conducted at our hospital from January 2022 to January 2023, the study involved 76 patients with liver-qi stagnation-type depression, divided into an observation group (acupuncture + cognitive therapy) and a control group (fluoxetine tablets), with 38 patients in each group. We assessed clinical efficacy, Hamilton Depression Scale (HAMD) scores, Self-Rating Depression Scale (SDS) scores, Traditional Chinese Medicine (TCM) syndrome scores, liver-qi stagnation syndrome main symptom scores, and serum levels of 5-hydroxytryptamine (HT), vasoactive intestinal peptide (VIP), and cAMP response element-binding protein (CREB) before and after treatment. The observation group achieved a total effective rate of 81.58%, significantly higher than the control group ( P < 0.05). Both groups showed significant reductions in HAMD and SDS scores, TCM syndrome scores, and liver-qi stagnation syndrome principal symptom scores posttreatment, with the observation group demonstrating superior improvements ( P < 0.05). Serum levels of 5-HT, VIP, and CREB also increased significantly in both groups, with greater changes in the observation group ( P < 0.05). The results suggest that the combination of acupuncture and cognitive therapy is more effective than fluoxetine alone in treating liver-qi stagnation-type depression, improving both clinical symptoms and physiological indicators.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"120-126"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tannic Acid Modulates Voltage-gated K + Channels to Promote Neuritogenesis in Neuronal N2A Cells.","authors":"Tien-Yao Tsai, Chin-Min Chuang, King-Chuen Wu, Zih-He Yang, Yuk-Man Leung","doi":"10.4103/ejpi.EJPI-D-24-00098","DOIUrl":"10.4103/ejpi.EJPI-D-24-00098","url":null,"abstract":"<p><strong>Abstract: </strong>In a previous report, we showed that voltage-gated K + (Kv) Kv1 and Kv2 channels are involved in cAMP-induced neuritogenesis of mouse neuronal N2A cells. In this report, we examined the effects of tannic acid (TA) on Kv channels and neuritogenesis in N2A cells. TA (15 μM) mildly enhanced Kv currents at -30 to -20 mV but strongly inhibited Kv currents at higher voltages, causing a preferential activation of currents at low voltages. When enhancement and suppression of Kv currents (at -20 and +70 mV, respectively) by different concentrations of TA were analyzed, TA at 4 μM produced strong enhancement at -20 mV with relatively mild suppression at + 70 mV. TA (4 μM) also promoted neuritogenesis; such promotion was suppressed by a Kv channel blocker tetraethylammonium ion, or a combination of hongotoxin-1 (blocker of Kv1.1), UK 78282 (blocker of Kv1.4) and guangxitoxin 1E (blocker of Kv2.1). Our results demonstrate, for the first time, TA at low concentrations could modulate Kv channels and thereby promote neuritogenesis.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"77-83"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Advillin Knockout on Diabetic Neuropathy Induced by Multiple Low Doses of Streptozotocin.","authors":"Yu-Chia Chuang, Bo-Yang Jiang, Chih-Cheng Chen","doi":"10.4103/ejpi.EJPI-D-24-00061","DOIUrl":"10.4103/ejpi.EJPI-D-24-00061","url":null,"abstract":"<p><strong>Abstract: </strong>Advillin is an actin-binding protein involved in regulating the organization of actin filaments and the dynamics of axonal growth cones. In mice, advillin is exclusively expressed in somatosensory neurons, ubiquitously expressed in all neuron subtypes during neonatal ages and particularly enriched in isolectin B4-positive (IB4 + ) non-peptidergic neurons in adulthood. We previously showed that advillin plays a key role in axon regeneration of somatosensory neurons during peripheral neuropathy. Mice lacking advillin lost the ability to recover from neuropathic pain induced by oxaliplatin, chronic compression of the sciatic nerve, and experimental autoimmune encephalitis. However, the role of advillin in painful diabetic neuropathy remains unknown. Diabetic neuropathy, a prevalent complication of types 1 and 2 diabetes mellitus, poses significant treatment challenges because of the limited efficacy and adverse side effects of current analgesics. Here we probed the effect of advillin knockout on neuropathic pain in a diabetic mouse model induced by multiple low doses of streptozotocin (STZ). STZ-induced cold allodynia was resolved in 8 weeks in wild-type ( Avil +/+ ) mice but could last more than 30 weeks in advillin-knockout ( Avil -/- ) mice. Additionally, Avi -/- but not Avil +/+ mice showed STZ-induced mechanical hypersensitivity of muscle. Consistent with the prolonged and/or worsened STZ-induced neuropathic pain, second-line coping responses to pain stimuli were greater in Avil -/- than Avil +/+ mice. On analyzing intraepidermal nerve density, STZ induced large axon degeneration in the hind paws but with distinct patterns between Avil +/+ and Avil -/- mice. We next probed whether advillin knockout could disturb capsaicin-induced axon regeneration ex vivo because capsaicin is clinically used to treat painful diabetic neuropathy by promoting axon regeneration. In a primary culture of dorsal root ganglion cells, 10-min capsaicin treatment selectively promoted neurite outgrowth of IB4 + neurons in Avil +/+ but not Avil -/- groups, which suggests that capsaicin could reprogram the intrinsic axonal regeneration by modulating the advillin-mediated actin dynamics. In conclusion, advillin knockout prolonged STZ-induced neuropathic pain in mice, which may be associated with the impaired intrinsic capacity of advillin-dependent IB4 + axon regeneration.</p>","PeriodicalId":519921,"journal":{"name":"Journal of physiological investigation","volume":" ","pages":"11-21"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}