Experimental AnimalsPub Date : 2024-07-09Epub Date: 2024-03-07DOI: 10.1538/expanim.23-0109
Tung-Sheng Chen, Wei-Wen Kuo, Chih-Yang Huang
{"title":"Autologous transplantation of green tea epigallocatechin-3-gallate pretreated adipose-derived stem cells increases cardiac regenerative capability through C-X-C motif chemokine receptor 4 expression in the treatment of rats with diabetic cardiomyopathy.","authors":"Tung-Sheng Chen, Wei-Wen Kuo, Chih-Yang Huang","doi":"10.1538/expanim.23-0109","DOIUrl":"10.1538/expanim.23-0109","url":null,"abstract":"<p><p>Cardiomyopathy is one of complications related to diabetes. Stem cell transplantation shows potential in diabetic cardiomyopathy treatment. Epigallocatechin-3-gallate (EGCG) is one of the major components found in green tea. Although stem cell transplantation and green tea EGCG supplementation show therapeutic effects on cardiomyopathy, the detailed cellular mechanisms in stem cell transplantation coupled with EGCG treatment remain unclear. This study investigates whether adipose-derived stem cells (ADSC) pretreated with EGCG show better protective effect on diabetic cardiomyopathy than ADSC without EGCG pretreatment. A cell model indicated that ADSC pretreated with EGCG increased cell functions including colony formation, migration and survival markers. All of these functions are blocked by small interfering C-X-C motif chemokine receptor 4 (siCXCR4) administration. These findings suggest that ADSC pretreatment with EGCG increases cell functions through CXCR4 expression. A diabetic animal model was designed to verify the above findings, including Sham, DM (diabetes mellitus), DM+ADSC (DM rats receiving autologous transplantation of ADSC) and DM+E-ADSC (DM rats receiving EGCG pretreated ADSC). Compared to the Sham, we found that all of pathophysiological signalings were activated in the DM group, including functional changes (decrease in ejection fraction and fractional shortening), structural changes (disarray and fibrosis) and molecular changes (increases in apoptotic, fibrotic, hypertrophic markers and decreases in survival and longevity markers). E-ADSC (DM+E-ADSC) transplantation shows significant improvement in the above pathophysiological signalings greater than ADSC (DM+ADSC). Therefore, ADSC pretreated with EGCG may contribute to clinical applications for diabetic patients with cardiomyopathy.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"246-258"},"PeriodicalIF":2.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2024-07-09Epub Date: 2024-02-07DOI: 10.1538/expanim.23-0171
Natsuki Mikami, Chi Lieu Kim Nguyen, Yuki Osawa, Kanako Kato, Miyuki Ishida, Yoko Tanimoto, Kento Morimoto, Kazuya Murata, Woojin Kang, Fumihiro Sugiyama, Masatsugu Ema, Satoru Takahashi, Seiya Mizuno
{"title":"Deletion of Exoc7, but not Exoc3, in male germ cells causes severe spermatogenesis failure with spermatocyte aggregation in mice.","authors":"Natsuki Mikami, Chi Lieu Kim Nguyen, Yuki Osawa, Kanako Kato, Miyuki Ishida, Yoko Tanimoto, Kento Morimoto, Kazuya Murata, Woojin Kang, Fumihiro Sugiyama, Masatsugu Ema, Satoru Takahashi, Seiya Mizuno","doi":"10.1538/expanim.23-0171","DOIUrl":"10.1538/expanim.23-0171","url":null,"abstract":"<p><p>Vesicular trafficking is essential for the transport of intracellularly produced functional molecules to the plasma membrane and extracellular space. The exocyst complex, composed of eight different proteins, is an important functional machinery for \"tethering\" in vesicular trafficking. Functional studies have been conducted in laboratory mice to identify the mechanisms by which the deletion of each exocyst factor affect various biological phenomena. Interestingly, each exocyst factor-deficient mutant exhibits a different phenotype. This discrepancy may be due to the function of the exocyst factor beyond its role as a component of the exocyst complex. Male germline-specific conditional knockout (cKO) mice of the Exoc1 gene, which encodes one of the exocyst factors EXOC1 (SEC3), exhibit severe spermatogenesis defects; however, whether this abnormality also occurs in mutants lacking other exocyst factors remains unknown. In this study, we found that exocyst factor EXOC3 (SEC6) was not required for spermatogenesis, but depletion of EXOC7 (EXO70) led to severe spermatogenesis defects. In addition to being a component of the exocyst complex, EXOC1 has other functions. Notably, male germ cell-specific Exoc7 cKO and Exoc1 cKO mice exhibited phenotypic similarities, suggesting the importance of the exocyst complex for spermatogenesis. The results of this study will contribute to further understanding of spermatogenesis from the aspect of vesicular trafficking.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"286-292"},"PeriodicalIF":2.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2024-07-09Epub Date: 2024-03-22DOI: 10.1538/expanim.23-0148
Julia Chu-Ning Hsu, Hsu-Wen Tseng, Chia-Hui Chen, Tzong-Shyuan Lee
{"title":"Transient receptor potential vanilloid 1 interacts with Toll-like receptor 4 (TLR4)/cluster of differentiation 14 (CD14) signaling pathway in lipopolysaccharide-mediated inflammation in macrophages.","authors":"Julia Chu-Ning Hsu, Hsu-Wen Tseng, Chia-Hui Chen, Tzong-Shyuan Lee","doi":"10.1538/expanim.23-0148","DOIUrl":"10.1538/expanim.23-0148","url":null,"abstract":"<p><p>Transient receptor potential vanilloid 1 (TRPV1), a ligand-gated cation channel, is a receptor for vanilloids on sensory neurons and is also activated by capsaicin, heat, protons, arachidonic acid metabolites, and inflammatory mediators on neuronal or non-neuronal cells. However, the role of the TRPV1 receptor in pro-inflammatory cytokine secretion and its potential regulatory mechanisms in lipopolysaccharide (LPS)-induced inflammation has yet to be entirely understood. To investigate the role and regulatory mechanism of the TRPV1 receptor in regulating LPS-induced inflammatory responses, bone marrow-derived macrophages (BMDMs) harvested from wild-type (WT) and TRPV1 deficient (Trpv1<sup>-/-</sup>) mice were used as the cell model. In WT BMDMs, LPS induced an increase in the levels of tumor necrosis factor-α, IL-1β, inducible nitric oxide synthase, and nitric oxide, which were attenuated in Trpv1<sup>-/-</sup> BMDMs. Additionally, the phosphorylation of inhibitor of nuclear factor kappa-Bα and mitogen-activated protein kinases, as well as the translocation of nuclear factor kappa-B and activator protein 1, were all decreased in LPS-treated Trpv1<sup>-/-</sup> BMDMs. Immunoprecipitation assay revealed that LPS treatment increased the formation of TRPV1-Toll-like receptor 4 (TLR4)-cluster of differentiation 14 (CD14) complex in WT BMDMs. Genetic deletion of TRPV1 in BMDMs impaired the LPS-triggered immune-complex formation of TLR4, myeloid differentiation protein 88, and interleukin-1 receptor-associated kinase, all of which are essential regulators in LPS-induced activation of the TLR4 signaling pathway. Moreover, genetic deletion of TRPV1 prevented the LPS-induced lethality and pro-inflammatory production in mice. In conclusion, the TRPV1 receptor may positively regulate the LPS-mediated inflammatory responses in macrophages by increasing the interaction with the TLR4-CD14 complex and activating the downstream signaling cascade.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"336-346"},"PeriodicalIF":2.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuroprotective effect of gallic acid in mice with rotenone-induced neurodegeneration.","authors":"Wachiryah Thong-Asa, Chatrung Wassana, Kunyarat Sukkasem, Pichcha Innoi, Montira Dechakul, Pattraporn Timda","doi":"10.1538/expanim.23-0165","DOIUrl":"10.1538/expanim.23-0165","url":null,"abstract":"<p><p>We investigated the effect of gallic acid (Gal) against neurodegenerative pathophysiology relevant to Parkinsion's disease (PD) in mice with rotenone-induced toxicity. Forty male institute of cancer research (ICR) mice were randomly divided into four groups: sham-veh, PD-veh (received subcutaneous injection with 2.5 mg/kg/48 h of rotenone); PD-Gal50; and PD-Gal100 (the latter two groups received subcutaneous injection with 2.5 mg/kg/48 h of rotenone and oral gavage with gallic acid 50 and 100 mg/kg/48 h, respectively). All treatments continued for 5 weeks with motor ability assessments once per week using hanging and rotarod tests. Brain tissue evaluation of oxidative status, together with striatal and substantia nigra par compacta (SNc) histological and immunohistological assessments were performed. The results indicate that rotenone significantly induced muscle weakness and motor coordination deficit from the first week of rotenone injection, and a significant increase in neuronal degeneration was presented in both the striatum and SNc. Decreased tyrosine hydroxylase and increment of glia fibrillary acidic protein expression in SNc were depicted. The deteriorating effects of rotenone were ameliorated by gallic acid treatment, especially 100 mg/kg dose. Rotenone did not induce a significant change of lipid peroxidation indicated, but gallic acid exhibited a significant inhibitory effect on the lipid peroxidation increment. Rotenone showed a significant reduction of superoxide dismutase activity, and neither 50 nor 100 mg/kg of gallic acid could alleviate this enzyme activity. In conclusion, gallic acid ameliorated motor deficits and preserving SNc neurons which led to maintaining of the dopaminergic source, including a nurturing effect on supporting astrocytes in mice with rotenone-induced neurodegeneration.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"259-269"},"PeriodicalIF":2.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myelin lesion in the aspartoacylase (Aspa) knockout rat, an animal model for Canavan disease.","authors":"Shuji Takeda, Rika Hoshiai, Miyuu Tanaka, Takeshi Izawa, Jyoji Yamate, Takashi Kuramoto, Mitsuru Kuwamura","doi":"10.1538/expanim.23-0089","DOIUrl":"10.1538/expanim.23-0089","url":null,"abstract":"<p><p>Canavan disease (CD) is a fatal hereditary neurological disorder caused by a mutation in the aspartoacylase (ASPA) gene and characterized by neurological signs and vacuolation in the central nervous system (CNS). The mutation inhibits the hydrolysis of N-acetyl-aspartate (NAA) resulting in accumulation of NAA in the CNS. A new Aspa-knockout rat was generated by transcription activator-like effector nuclease (TALEN) technology. Herein we describe the pathological and morphometrical findings in the brain and spinal cords of Aspa-knockout rats. Although Aspa-knockout rats did not show any neurological signs, vacuolation with swollen axons, hypomyelination, and activated swollen astrocytes were observed mainly in the brainstem reticular formation, ascending and descending motor neuron pathway, and in the olfactory tract. Morphometrical analysis revealed no obvious change in the number of neurons. These changes in the CNS are similar to human CD, suggesting that this animal model would be useful for further study of treatment and understanding the pathophysiology of human CD.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"347-356"},"PeriodicalIF":2.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment and visual analysis of CBA/J-Pde6b<sup>Y347Y/Y347X</sup> and C3H/HeJ-Pde6b<sup>Y347Y/Y347X</sup> mice.","authors":"Miyuki Shindo, Miho Terao, Shuji Takada, Minoru Ichinose, Emiko Matsuzaka, Tadashi Yokoi, Noriyuki Azuma, Seiya Mizuno, Hideki Tsumura","doi":"10.1538/expanim.23-0142","DOIUrl":"10.1538/expanim.23-0142","url":null,"abstract":"<p><p>In CBA/J and C3H/HeJ mice, retinitis pigmentosa is inherited as an autosomal-recessive trait due to a mutation in Pde6b, which encodes cGMP phosphodiesterase subunit b. In these strains, the Y347X mutation in Pde6b leads to the upregulation of cGMP levels, increased Ca<sup>2+</sup> influx induces rod death, and the outer segment and rod cells entirely disappeared by 35 days after birth. In the present study, we utilized the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9-mediated gene editing to repair the Y347X mutation in CBA/J and C3H/HeJ mice. Evaluation of the established CBA/J-Pde6b<sup>Y347Y/Y347X</sup> and C3H/HeJ-Pde6b<sup>Y347Y/Y347X</sup> mice, which were confirmed to have normal retinal layers by live fundoscopic imaging and histopathological analysis, revealed improved visual acuity based on the visual cliff and light/dark latency tests. Furthermore, our analyses revealed that the visible platform test was a more effective tool for testing visual behavior in these mice. The results suggest that the established strains can serve as control groups for CBA/J and C3H/HeJ in ophthalmology studies involving retinitis pigmentosa.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"203-210"},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment of spontaneously hypertensive rats during pregnancy and lactation with the antioxidant tempol lowers blood pressure and reduces oxidative stress.","authors":"Kohei Kawakami, Hiroyuki Matsuo, Naoyo Kajitani, Ken-Ichi Matsumoto","doi":"10.1538/expanim.23-0069","DOIUrl":"10.1538/expanim.23-0069","url":null,"abstract":"<p><p>Genetic and environmental factors interact in a complex manner in the pathogenesis of essential hypertension in humans. Oxidative stress is considered one of the more important environmental factors. We used the spontaneously hypertensive rat (SHR) model to test whether continuous feeding with the antioxidant tempol reduces maternal oxidative stress during pregnancy and potentially contributes to the prevention of cardiovascular disease onset. Pregnant female rats were divided into control and tempol-treated groups. Tempol was continuously administered in drinking water. The administration period lasted approximately 40 days, from the confirmation of a vaginal plug until birth of the pups and their subsequent weaning. The blood pressure (BP) of each adult female was measured three times during pregnancy and post parturition. Milk was collected three times from nursing mother rats in the immediate postpartum period. Markers of oxidative stress were measured: 8-hydroxyl-2'-deoxyguanosine (8-OHdG) levels in milk during the experimental period and 8-OHdG and corticosterone levels in urine of adult and neonatal rats. The urinary level of 8-OHdG in the tempol-treated group was significantly lower than that in the control group. Corticosterone levels were significantly lower in urine of neonatal rats from the tempol-treated group compared with the levels of the control group. The levels of total antioxidant in milk were significantly greater in the tempol-treated group than in the control group. This study demonstrated that continuous administration of tempol to pregnant SHRs reduced maternal oxidative stress and contributed to reduced oxidative stress in neonatal rats.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"136-144"},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2024-05-03Epub Date: 2023-12-15DOI: 10.1538/expanim.23-0145
Na Ahn, Jaehak Park, Jungjoon Ihm, Sangho Roh
{"title":"A survey of the impact of COVID-19 on the management of animal experiments and laboratory animal facilities in Korea.","authors":"Na Ahn, Jaehak Park, Jungjoon Ihm, Sangho Roh","doi":"10.1538/expanim.23-0145","DOIUrl":"10.1538/expanim.23-0145","url":null,"abstract":"<p><p>The pandemic has affected the lives of people all over the world. The effects of the pandemic on laboratory animal facilities and their operations through this unusual global event are poorly understood. Here, we have applied a methodological framework of qualitative approach including semi-structured interviews to investigate laboratory animal operations in Korea and how it has shaped the on-going management and laboratory operations of such facilities. A total of fifty-two individuals, including members and administrators of the Institutional Animal Care and Use Committee (IACUC), researchers, and animal facility managers and staff, were surveyed through purposeful sampling. Survey questions explored how the pandemic impacted the IACUC and the functioning of animal facilities, and what steps to take in preparation of a future pandemic-like crisis. Our survey found evidence of an increase in animal experiments in Korea during the pandemic that correlated with increases in research funding during that period, such as for vaccine development. Also, operational challenges due to pandemic-related health issues in personnel were resolved through overtime, rather than by reducing facility operations. Moreover, a refinement of post-approval monitoring (PAM) practices was also discussed by respondents. Taken together, our study offers insights into animal facility operations during the pandemic and outlines recommendations for safeguarding operations in such future scenarios.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"193-202"},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ivabradine ameliorates cardiomyopathy progression in a Duchenne muscular dystrophy model rat.","authors":"Ryota Tochinai, Koichi Kimura, Takeru Saika, Wataru Fujii, Hiroyuki Morita, Koki Nakanishi, Yoshiharu Tsuru, Shin-Ichi Sekizawa, Keitaro Yamanouchi, Masayoshi Kuwahara","doi":"10.1538/expanim.23-0087","DOIUrl":"10.1538/expanim.23-0087","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy caused by dystrophin mutations. Inevitable progressive cardiomyopathy is a current leading cause of premature death although respiratory management has improved the prognosis of patients with DMD. Recent evidence shows that reducing the heart rate is expected as one of the promising strategies for heart failure treatment, but administering a sufficient dose of β-blocker for patients with DMD with tachycardia is difficult because of their low blood pressure (BP). Thus, this study aimed to clarify the role of ivabradine, which suppresses cardiac sinus node pacemakers without decreasing BP, in ameliorating cardiomyopathy progression in a rat model with DMD. A trans-oral single ivabradine administration demonstrated a declined dose-dependent heart rate without any significant BP reduction. Trans-gastric repeated administrations of 5 mg/kg of ivabradine twice a day for 3 months showed ameliorated cardiomyopathy in DMD rats based on echocardiography and histopathological observations (left ventricular dysfunction, right ventricular dysfunction, and myocardial fibrosis) as compared with vehicle administration.Our finding indicates that ivabradine is expected as another treatment choice for patients with DMD having tachycardia.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"145-153"},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71422006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2024-05-03Epub Date: 2023-11-29DOI: 10.1538/expanim.23-0092
Haiqing Zhang, Zunlin Zhou, Jiyao Qin, Juan Yang, Hao Huang, Xiaoyan Yang, Zhong Luo, Yongsu Zheng, Yan Peng, Ya Chen, Zucai Xu
{"title":"Transmembrane protein modulates seizure in epilepsy: evidence from temporal lobe epilepsy patients and mouse models.","authors":"Haiqing Zhang, Zunlin Zhou, Jiyao Qin, Juan Yang, Hao Huang, Xiaoyan Yang, Zhong Luo, Yongsu Zheng, Yan Peng, Ya Chen, Zucai Xu","doi":"10.1538/expanim.23-0092","DOIUrl":"10.1538/expanim.23-0092","url":null,"abstract":"<p><p>Transmembrane protein (TMEM230) is located in secretory/recycling vesicles, including synaptic vesicles in neurons. However, the functional relationship between TMEM230 and epilepsy is still a mystery. The aims of this study were to investigate the expression of TMEM230 in patients with temporal lobe epilepsy (TLE) and two different mice models of chronic epilepsy, and to determine the probable roles of TMEM230 in epilepsy. Our results showed that TMEM230 expression was increased in the temporal neocortex of epileptic patients and the hippocampus and cortex of epileptic mice compared with that in the control tissues. Moreover, TMEM230 was mainly expressed in the neurons in both humans and mice epileptic brain. TMEM230 co-localized with glutamate vesicular transporter 1 (VGLUT-1), but not with vesicular γ-aminobutyric acid (GABA) transporter (VGAT). Mechanistically, coimmunoprecipitation confirmed that TMEM230 interacted with VGLUT-1, but not with VGAT in the hippocampus of epileptic mice. Lentivirus mediated overexpression of TMEM230 increased mice susceptibility to epilepsy and behavioural phenotypes of epileptic seizures during the kainite (KA)-induced chronic phase of epileptic seizures and the pentylenetetrazole (PTZ) kindling process, whereas lentivirus-mediated TMEM230 downregulation had the opposite effect. These results shed light on the functions of TMEM230 in neurons, suggesting that TMEM230 may play a critical role in the regulation of epileptic activity via influencing excitatory neurotransmission.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"162-174"},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}