IBRO Neuroscience Reports最新文献

{"title":"Long COVID is associated with female sex; Anti-NCAM1 autoantibodies are absent in patients with long COVID","authors":"Yukiko Motokawa ,&nbsp;Jun Sugihara ,&nbsp;Tomoya Tateishi ,&nbsp;Tadashi Hosoya ,&nbsp;Shinsuke Yasuda ,&nbsp;Yasunari Miyazaki ,&nbsp;Hidehiko Takahashi ,&nbsp;Hiroki Shiwaku","doi":"10.1016/j.ibneur.2025.07.002","DOIUrl":"10.1016/j.ibneur.2025.07.002","url":null,"abstract":"<div><h3>Background</h3><div>Long COVID is a condition that may arise following SARS-CoV-2 infection and is associated with a range of systemic complications. Autoantibodies are implicated in the pathogenesis of long COVID. However, the details of the pathogenic mechanisms undergone by these autoantibodies remain unclear. Neural cell adhesion molecule 1 (NCAM1) is the human protein with the highest sequence homology to the SARS-CoV-2 proteins. Previous in silico studies indicate that SARS-CoV-2 infection may induce the production of anti-NCAM1 autoantibodies. Thus, this study investigated the presence of anti-NCAM1 autoantibodies in individuals affected by COVID-19, including those with long COVID.</div></div><div><h3>Methods</h3><div>Serum samples were obtained from 173 individuals 3 months after SARS-CoV-2 infection. Among them, 63 were diagnosed with long COVID. A cell-based assay was used to assess all 173 serum samples for the presence of anti-NCAM1 autoantibodies. We also analyzed the clinical profiles of patients with and without long COVID to identify potential risk factors associated with long COVID.</div></div><div><h3>Results</h3><div>Anti-NCAM1 autoantibodies were not detected in any serum sample. The proportion of female patients in the long COVID group was significantly higher than that in the non-long COVID group.</div></div><div><h3>Conclusion</h3><div>The results indicate that the production of anti-NCAM1 autoantibodies following COVID-19 is unlikely. Female sex is associated with higher risk of long COVID.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 252-256"},"PeriodicalIF":2.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596433","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":"Olfactory training in specific anosmia to androstenone and its association with genetic variations of OR7D4","authors":"Antonia Gillmeister ,&nbsp;Maira Harume Nagai ,&nbsp;Christian Margot ,&nbsp;Priyanka Meesa ,&nbsp;Hiroaki Matsunami ,&nbsp;Thomas Hummel","doi":"10.1016/j.ibneur.2025.06.017","DOIUrl":"10.1016/j.ibneur.2025.06.017","url":null,"abstract":"<div><div>Short-term, repeated exposure to odors, “olfactory training” (OT), improves olfactory function. Clinically, this works not only for trauma- or disease-related olfactory impairment but also in people with specific anosmia. Androstenone is an odorant for which the frequent occurrence of specific anosmia is already known. It is an odorous steroid derived from testosterone. Besides some people who cannot perceive the odor, it is perceived differently by different individuals in terms of odor quality. These differences in the ability to perceive androstenone as well as in the perception of its quality were previously related to single nucleotide polymorphisms of the human olfactory receptor OR7D4. The current study addressed the question of whether changes in the perception of androstenone in relation to a change in sensitivity following specific OT with that odorant are associated with genetic variations of OR7D4. A total of 335 healthy volunteers participated (206 females, 129 males). All participants underwent tests for normal olfactory function; 103 showed specific anosmia for androstenone. Seventy-seven participants initially unable to perceive androstenone performed OT for an average duration of 8 weeks. Detection thresholds as well as subjective evaluation of odor intensity and pleasantness were measured both before and after OT. Buccal swabs were taken to examine the OR7D4 genotype. The study provided the following major results: (1) Detection thresholds were significantly lower after OT. (2) There was no statistically significant impact of the OR7D4 genotype on the ability to perceive androstenone after OT. In conclusion, it appears that the ability to perceive androstenone can be trained in people with specific anosmia, although OR7D4 polymorphisms were not related to a major change in the sensitivity towards androstenone.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 245-251"},"PeriodicalIF":2.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572718","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":"Downregulation of AKT-mediated p27Kip1 phosphorylation with shift to sphingomyelin synthesis in CLN3 disease","authors":"Fatima Bilal ,&nbsp;Jihane Soueid ,&nbsp;Sara Saab ,&nbsp;Nadine Makhoul ,&nbsp;Zeinab Hamze ,&nbsp;Lara El-Bazzal ,&nbsp;Joelle Makoukji ,&nbsp;Rose-Mary Boustany","doi":"10.1016/j.ibneur.2025.06.005","DOIUrl":"10.1016/j.ibneur.2025.06.005","url":null,"abstract":"<div><div>CLN3 disease is a fatal childhood neurodegenerative disorder without drug-modifying therapies. Wild-type <em>CLN3</em> gene is anti-apoptotic. Previous work proves that CLN3 disease pathogenesis is associated with reduced cell viability/apoptotic cell death and increase in ceramide, in cells and brains of patients and in <em>Cln3</em>^{<em>Δex7/8</em>} mouse brain. AKT, a serine/threonine protein kinase, is at the core of a complex signaling pathway regulating apoptosis and cell proliferation and is neuroprotective. AKT fulfils this function via cyclin-dependent kinase inhibitor p27^Kip1 phosphorylation at residue T198 resulting in its cytoplasmic localization and promotion of cell survival. Transcriptomic analysis of gene expression using microarrays, validation by Western blot and real-time PCR, demonstrate that AKT is downregulated in CLN3-deficient cells and <em>Cln3</em>^{<em>Δex7/8</em>} mouse brain. Conversely, CLN3 overexpression causes upregulation of AKT proteins. Novel data shows that CLN3 deficiency reduces AKT-mediated p27^Kip1 T198 phosphorylation, possibly leading to reduced cell viability. Dysregulation in AKT/p27^Kip1 signaling alters sphingolipid metabolism. Results confirm an increase in sphingomyelin synthesis in CLN3-deficient cells.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 223-234"},"PeriodicalIF":2.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535205","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 combined effects of motor imagery and motor practice are influenced by differences in working memory function: Examination of brain, spinal cord, and muscle performance data","authors":"Yuki Fukumoto ,&nbsp;Hiroki Bizen ,&nbsp;Marina Todo ,&nbsp;Naoki Yoshida ,&nbsp;Toshiaki Suzuki","doi":"10.1016/j.ibneur.2025.06.016","DOIUrl":"10.1016/j.ibneur.2025.06.016","url":null,"abstract":"<div><div>The ability to perform motor imagery is affected by differences in short-term memory storage capacity in terms of the activation of working memory. Therefore, from the viewpoint of the simultaneous measurement of brain activation and spinal motor neuron excitability, we examined differences in the combined effects of motor practice and motor imagery due to differences in working memory function. 20 healthy individuals were classified into Normal (score of ≤5–6 digits) and Good (score of ≥7 digits) groups based on working memory in a digit span test. Following this, participants performed six sets of repetitive exercises combining motor practice and motor imagery, and changes in neural activity patterns in the brain and spinal cord, as well as changes in finger dexterity, were tracked. In brain network analysis, the first execution of the imagery showed high Betweenness Centrality in the frontal pole cortex, which shifted to the dorsolateral prefrontal cortex with repeated imagery. The involvement of the frontal pole may reflect introspection of motor behavior in the initial stage, while the dorsolateral prefrontal cortex consistently participated in imagery generation throughout the entire motor imagery process. In addition, both groups showed improvement in finger dexterity after intervention, but during repetitive motor imagery, a decrease in amplitude F/M ratio was observed in the Good Working Memory group, and a decrease in activation of the right primary motor cortex was observed in the Normal Working Memory group. In terms of working memory, especially in aspects of the phonological loop, those with higher function may execute motor imagery more distinctly.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 210-222"},"PeriodicalIF":2.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501695","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":"Electrophysiological analysis of distal, proximal, and dual compression of the median nerve","authors":"Qiongfang Zhang ,&nbsp;Yongfeng Liu ,&nbsp;Jinhuan Zhang ,&nbsp;Yirong Chen ,&nbsp;Xingxian Huang ,&nbsp;Haibo Yu","doi":"10.1016/j.ibneur.2025.06.010","DOIUrl":"10.1016/j.ibneur.2025.06.010","url":null,"abstract":"<div><h3>Objective</h3><div>Both distal and proximal compression of the median nerve can lead to hand numbness inpatients.This study aimed to dissect the electrophysiological characteristics of median nerve motor fibers inpatients with carpal tunnel syndrome (CTS) caused by distal median nerve compression, C8 - T1 nerve root - type cervical spondylosis (CRS) resulting from proximal median nerve compression, and double - compression syndrome (DCS) with CTS combined with C8 - T1 CRS, so as to verify the double - nerve compression theory, provide evidence-based basis for clinical treatment.</div></div><div><h3>Methods</h3><div>Retrospective analysis of 30 subjects per group (CTS, CRS, DCS, controls) from a neurophysiological database. Parameters included distal motor latency (DML1-wrist, DML2-elbow), compound muscle action potential (CMAP1, CMAP2), wrist-elbow motor conduction velocity (MCV), and F-wave latency.</div></div><div><h3>Results</h3><div>For each indicator, both the CTS group and the DCS group showed statistically significant differences from the normal group. When comparing between the CTS group and the DCS group, there were no statistically significant differences in all data indicators. When comparing the CRS group with the normal group, there were no statistically significant differences in DML1 and DML2, but there were statistically significant differences in the shortest latency of the F wave and the motor conduction velocity (MCV).</div></div><div><h3>Conclusion</h3><div>Double compression does not cause more severe damage to the nerve compared with simple distal compression. Distal compression of the median nerve causes more severe damage to the peripheral nerve than proximal compression. For patients with double compression syndrome, clinical treatment should prioritize the treatment of the distal compression site.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 205-209"},"PeriodicalIF":2.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470941","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":"Uptakes of boronophenylalanine in the in vitro and in situ glioblastoma and the potential efficacy of boron neutron capture therapy","authors":"Shining Zhang ,&nbsp;Yujie Wei ,&nbsp;Wenjiao Gu ,&nbsp;Shuangyi Li ,&nbsp;Ting Liu ,&nbsp;Limei Shuai ,&nbsp;Yu Tang ,&nbsp;Ying Jiang ,&nbsp;Xiaochun Zhou ,&nbsp;Yucai Wei ,&nbsp;Guan Wang ,&nbsp;Long Gu ,&nbsp;Yumin Li ,&nbsp;Futian Tang ,&nbsp;Daiying Zuo","doi":"10.1016/j.ibneur.2025.06.014","DOIUrl":"10.1016/j.ibneur.2025.06.014","url":null,"abstract":"<div><div>Human glioblastoma (GBM) is the most malignant brain tumor. Boron neutron capture therapy (BNCT) is proved to be a new technology for the effective treatment of GBM. We previously reported that boronophenylalanine (BPA), the boron drug used in BNCT prefers to the tumor of a mouse subcutaneous tumor model injected U87 and GL261, two GBM cell lines. The present study was designed to investigate the distribution of BPA in the tumor of a mouse <em>in situ</em> brain tumor model injected U87 and GL261 in the brain. The tumor model was evaluated by using small animal magnetic resonance imaging (MRI) and confirmed with the morphological observations. The boron concentration indicative of BPA in cells and tumor was measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results revealed that the protein of L-type amino acid transporter (LAT1) was highly expressed in both U87 and GL261 cells. In addition, boron concentration in U87 and GL261 cells was increased 1, 2, 3, 5 and 7 h after addition of BPA in a time-dependently manner. However, the boron concentration in the cells was rapidly decreased when the BPA in the medium was withdrawn for 1 h at each time point, reaching almost the same levels between the time points. In one mouse <em>in situ</em> brain tumor model injected U87 cells, the concentration of boron in the tumor tissue (25.529 μg/g) was higher than that in brain tissue (8.973 μg/g), blood (11.407 μg/g), heart (13.131 μg/g), liver (11.271 μg/g), spleen (15.631 μg/g) and lung (16.226 μg/g) respectively, having ratios of tumor/normal tissue 2.845, 2.238, 1.944, 2.265, 1.633 and 1.537 respectively. Similarly, in another mouse <em>in situ</em> brain tumor model injected GL261 cells, the concentration of boron in the tumor tissue (23.039 μg/g) was higher than that in brain tissue (8.141 μg/g), blood (9.573 μg/g), heart (12.119 μg/g), liver (9.609 μg/g), spleen (15.852 μg/g) and lung (12.565 μg/g) respectively, having ratios of tumor/normal tissue 2.831, 2.407, 1.901, 2.398, 1.453 and 1.834 respectively. The results suggest that uptakes of BPA in two cell lines occur in a time-dependent manner and that BPA preferred to distribute in brain tumor tissue than other normal tissues, having potential efficacy of BNCT.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 192-197"},"PeriodicalIF":2.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470939","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":"Mozart for the brain - a pilot study on physiological effects of auditive stimulation in patients after aneurysmal subarachnoid hemorrhage","authors":"Nicolas Eden ,&nbsp;Marius Marc-Daniel Mader ,&nbsp;Jan Bremer ,&nbsp;Jennifer Sauvigny ,&nbsp;Jörn Grensemann ,&nbsp;Marlene Fischer ,&nbsp;Nils Schweingruber ,&nbsp;Jens Gempt ,&nbsp;Patrick Czorlich","doi":"10.1016/j.ibneur.2025.06.008","DOIUrl":"10.1016/j.ibneur.2025.06.008","url":null,"abstract":"<div><h3>Background</h3><div>Classical music influences human physiology, such as the cerebral blood flow velocity (CBFV), in healthy controls and during recovery from ischemic stroke. Aim of this prospective pilot-study was to investigate the effect of classical music on CBFV and other physiological parameters in patients suffering from aneurysmal subarachnoid hemorrhage (SAH).</div></div><div><h3>Methods</h3><div>Twenty patients with SAH were subjected to up to three interventions, in which the patients listened to <em>W. A. Mozart's Symphony No. 40 in G minor</em>. In parallel, CBFV in the right middle cerebral artery (MCA) was continuously measured using transcranial Doppler (TCD). TCD values were averaged per minute, normalized, and analyzed with a mixed-effects linear regression model. In addition, other physiological and laboratory parameters were evaluated.</div></div><div><h3>Results</h3><div>A total of 55 interventions were successfully carried out. The mixed-effects linear regression model revealed significant associations with both time (p &lt; 0.001) and session (p = 0.002), specifically, with each minute of classical music played, there was a 0.3 % reduction in CBFV (95 % confidence interval (CI): 0.2–0.4 %). Heart rate (HR) and respiratory rate (RR) decreased by 0.1 % (95 % CI: −0.2–0.0 %; p = 0.043) 0.3 % (95 % CI: −0.6 % to −0.1 %; p = 0.001), respectively, per minute of exposure. Each additional session resulted in a reduction of HR by 4.3 % and RR by 22.3 % from the baseline at the start of the intervention to minute 25 (both p &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Our pilot study shows only a very small effect of classical music such as Mozart's Symphony No. 40 in G <em>minor</em> in patients with SAH.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 198-204"},"PeriodicalIF":2.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470940","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":"Evaluation of sleep quality and its determinants among individuals with diabetes mellitus and/or hypertension: A cross-sectional study","authors":"John Dogah ,&nbsp;Ansumana Bockarie ,&nbsp;Eric Kwame Kunkah ,&nbsp;Adwoa Abrafi Boampong ,&nbsp;George Nkrumah Osei ,&nbsp;Kwasi Baffour Gyimah ,&nbsp;Stephen Teye ,&nbsp;Esther Marfo ,&nbsp;David Mawutor Donkor ,&nbsp;David Larbi Simpong","doi":"10.1016/j.ibneur.2025.06.015","DOIUrl":"10.1016/j.ibneur.2025.06.015","url":null,"abstract":"<div><h3>Background</h3><div>Sleep difficulties are common, especially among people with chronic illnesses like diabetes mellitus and hypertension, which significantly impact health and survival. This study assessed sleep quality and factors associated with poor sleep quality in individuals with diabetes mellitus (DM) and/or hypertension.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted at Mampong Government Hospital. Socio-demographic and lifestyle data, including age, sex, occupation, marital status, alcohol consumption, and physical activity levels, were collected via a structured questionnaire. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and data analysis was performed using Chi-square tests and binary logistic regression with IBM SPSS version 27.</div></div><div><h3>Results</h3><div>The study included 201 participants, with findings indicating that 41.3 % experienced poor sleep. Poor sleep was most prevalent among individuals with both DM and hypertension, affecting 37 out of 88 participants. Analysis of the PSQI components indicated that participants consistently scored above 1 in subjective sleep quality, sleep latency, and sleep disturbance, reflecting considerable sleep challenge. Married participants showed a higher prevalence of poor sleep (55.4 %), while those involved in mild physical activity reported the highest prevalence of poor sleep (69.9 %). Poor sleep was significantly associated with marital status, education level, and intensity of physical activity. Among participants with both diabetes mellitus and hypertension, those aged 41–60 had significantly higher odds of poor sleep compared to those aged 20–40 (aOR = 10.584, p = 0.043, 95 % CI: 1.081–103.592).</div></div><div><h3>Conclusion</h3><div>Poor sleep is common among individuals with diabetes mellitus and hypertension. The findings reinforce the importance of integrating sleep quality assessments into the management of chronic conditions to support overall health and well-being.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 143-147"},"PeriodicalIF":2.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365668","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":"PKD1-mediated phosphorylation at dopamine D2 receptor serine 365 site in dorsal striatum underlies cocaine-induced locomotor hyperactivity","authors":"Xinyu Zhang ,&nbsp;Ziran Zhang ,&nbsp;Ying Wang ,&nbsp;Linlin Sun ,&nbsp;Ning Wang","doi":"10.1016/j.ibneur.2025.06.013","DOIUrl":"10.1016/j.ibneur.2025.06.013","url":null,"abstract":"<div><div>Locomotor hyperactivity is an early behavioural adaptation in cocaine use disorder, driven by increased dopamine levels in the striatum. The expression, sensitivity, and availability of dopamine D2 receptor (D2R) are significantly associated with cocaine use disorder. However, neither D2R agonists nor antagonists are optimal for clinical intervention because of their side effects. Therefore, targeting regulatory proteins that can effectively disrupt cocaine-induced D2R malfunction may offer improved strategies for cocaine use disorder. Here, we report that knockdown of protein kinase D1 (PKD1) in the rat dorsal striatum attenuates cocaine-induced locomotor hyperactivity. PKD1 phosphorylates the serine 365 site (S365) of D2R, reduces its surface localisation, and enhances downstream extracellular signal-regulated kinase (ERK) signalling. Tat-S365, an engineered Tat fusion-peptide blocked S365 phosphorylation in D2R, thereby decreasing the pERK levels. <em>In vivo</em> injection of peptide Tat-S365 into the rat dorsal striatum successfully inhibited cocaine-induced locomotor hyperactivity. Thus, targeting S365 of D2R presents a promising strategy for developing pharmacotherapeutic treatments for cocaine sensitisation and other disorders that result from dopamine imbalances.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 124-132"},"PeriodicalIF":2.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321668","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":"Synergistic effects of PAR2 and TrkA exacerbate visceral hypersensitivity induced by chronic pancreatitis in rats","authors":"Zhiyun Liu ,&nbsp;Jiao Zhu ,&nbsp;Qianbo Chen ,&nbsp;Kunming Tao ,&nbsp;Kai Wei ,&nbsp;Xiaodan Wu ,&nbsp;Haibo Qiu ,&nbsp;Zhijie Lu","doi":"10.1016/j.ibneur.2025.06.012","DOIUrl":"10.1016/j.ibneur.2025.06.012","url":null,"abstract":"<div><h3>Background</h3><div>Abdominal pain is the most severe symptom of chronic pancreatitis. However, till date, there are only a few studies on the mechanism of pain in chronic pancreatitis. Previous research has reported that mast cells are enriched around nerve fibers and are associated with visceral pain. In this study, we aimed to investigate the molecular mechanisms by which protease-activated receptor 2 (PAR2) and tropomyosin receptor kinase A (TrkA) exacerbate pain in chronic pancreatitis.</div></div><div><h3>Methods</h3><div>A chronic pancreatitis animal model was established by injecting dibutyltin dichloride into the tail vein of Wistar rats. The von Frey test was performed to evaluate pain behavior in the rats. Hematoxylin and eosin staining, western blotting, immunofluorescence histochemistry, retrograde labeling, culture of dorsal root ganglion (DRG) neurons, and whole-cell patch clamp recordings were performed to illustrate the mechanisms.</div></div><div><h3>Results</h3><div>The pancreatic structures were destroyed, including inflammatory cell infiltration and acinar atrophy, and mast cells were dramatically recruited to the pancreatic tissue in chronic pancreatitis. Systemic administration of the mast cell stabilizer ketotifen alleviated chronic pancreatitis-induced visceral hypersensitivity in the Wistar rat model. In contrast, the mast cell secretagogue compound 48/80 dose-dependently exacerbated chronic pancreatitis pain. Furthermore, the number of DRG neurons projected into the pancreas was significantly increased by injecting Dil stain in chronic pancreatitis rat models and normal rats. The co-expression of PAR2 and TrkA was only observed in small-diameter DRG neurons containing transient receptor potential vanilloid 1 channel and was significantly higher than those in normal rats. Finally, we demonstrated the functional interaction between PAR2 and TrkA by whole-cell patch clamp recordings.</div></div><div><h3>Conclusions</h3><div>Mast cells contribute to chronic pancreatitis pain through enrichment and degranulation. The interaction of PAR2 and TrkA exacerbates chronic pancreatitis pain, which may be a potential strategy for the treatment of chronic pancreatitis -induced visceral pain.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 235-244"},"PeriodicalIF":2.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549062","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}