IBRO Neuroscience Reports最新文献

{"title":"Genetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice","authors":"Gabriela N. Vaz ,&nbsp;Flávia C. Turcato ,&nbsp;Isabel A.V. Lima ,&nbsp;Franciele F. Scarante ,&nbsp;Melissa R. Araújo ,&nbsp;Tamires A.V. Brigante ,&nbsp;Livia C.M. Rodrigues ,&nbsp;Francisco S. Guimarães ,&nbsp;Jaime E.C. Hallak ,&nbsp;Jose A. Crippa ,&nbsp;Antonio L. Teixeira ,&nbsp;Antonio C.P. de Oliveira ,&nbsp;Alline Cristina Campos","doi":"10.1016/j.ibneur.2024.06.002","DOIUrl":"10.1016/j.ibneur.2024.06.002","url":null,"abstract":"<div><p>About one-third of major depressive disorder (MDD) patients demonstrate unresponsiveness to classic antidepressants, and even the clinical efficacy of fast-acting drugs such as ketamine varies significantly among patients with treatment-resistant depression. Nevertheless, the lack of suitable animal models that mimic a possible ketamine-resistant phenotype challenges the understanding of resistance to drug treatment. In this study, we showed that PI3Kγ knock-out (KO) mice do not respond to classical doses of ketamine and classical antidepressants. PI3Kγ KO mice were unresponsive to both the rapid and sustained antidepressant-like effects of a single dose of ketamine in the forced swimming test. Additionally, they were unresponsive to the antidepressant-like effects induced by the tricyclic antidepressant imipramine and the selective serotonin reuptake inhibitor fluoxetine. However, acute pharmacological inhibition of PI3Kγ did not block the antidepressant-like effect of ketamine, showing that a chronic deficiency of the PI3Kγ-mediated pathway is necessary for the effects of classic doses of ketamine and antidepressants. Therefore, we propose that PI3Kγ participates in the antidepressant activity and is likely implicated in the neurobiology and phenotype observed in patients with MDD who demonstrate treatment resistance.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 87-95"},"PeriodicalIF":2.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000599/pdfft?md5=61fe70c91c2e1afdf5941559f701a1b1&pid=1-s2.0-S2667242124000599-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141411960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dickopff 1 inhibits cancer stem cell properties and promotes neuronal differentiation of human neuroblastoma cell line SH-SY5Y","authors":"Shubham Krishna ,&nbsp;Bharat Prajapati ,&nbsp;Pankaj Seth ,&nbsp;Subrata Sinha","doi":"10.1016/j.ibneur.2024.05.010","DOIUrl":"10.1016/j.ibneur.2024.05.010","url":null,"abstract":"<div><p>Neuroblastomas are pediatric tumors arising from undifferentiated cells of neural crest origin with stem cell-like characteristics. Dysregulation of Wnt/β-catenin signaling has been shown to be linked to the development of various tumors. Activated Wnt signaling results in β-catenin accumulation in the nucleus to support pro-neoplastic traits. DKK1, a secreted glycoprotein, is an inhibitor of Wnt signaling, and the addition of DKKI to the culture medium has been used to suppress the Wnt pathway. This study aimed to analyze the role of Dickopff-1 as a potential differentiating agent for the neuroblastoma cell line SH-SY5Y and neurospheres derived from it. The treatment of SH-5Y5Y derived neurospheres by DKK1 resulted in their disintegration and reduced proliferation markers like Ki67, PCNA. DKK1 treatment to the neurospheres also resulted in the loss of cancer stem cell markers like CD133, KIT and pluripotency markers like SOX2, OCT4, NANOG. DKK1 treatment caused reduction in mRNA expression of β-catenin and TCF genes like TCF4, TCF12. When the SH-SY5Y cancer cells were grown under differentiating conditions, DKKI caused neuronal differentiation by itself, and in synergy with retinoic acid. This was verified by the expression of markers like MAPT, DCX, GAP43, ENO2 and also with changes in neurite length. We concluded that Wnt inhibition, as exemplified by DKK1 treatment, is therefore a possible differentiating condition and also suppresses the proliferative and cancer stemness related properties of SH-SY5Y neuroblastoma cells.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 73-82"},"PeriodicalIF":2.0,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000551/pdfft?md5=68e74b55346fdc06761ed60ffaff0810&pid=1-s2.0-S2667242124000551-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141280676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The increasing authorship trend in neuroscience: A scientometric analysis across 11 countries","authors":"Ann Paul ,&nbsp;Mariella Segreti ,&nbsp;Pierpaolo Pani ,&nbsp;Emiliano Brunamonti ,&nbsp;Aldo Genovesio","doi":"10.1016/j.ibneur.2024.05.012","DOIUrl":"https://doi.org/10.1016/j.ibneur.2024.05.012","url":null,"abstract":"<div><p>Previous studies have demonstrated an increasing trend of the number of authors across various fields over the years. This trend has been attributed to the necessity for larger collaborations and, at times, to ethical issues regarding authorship attribution. Our study focuses on the evolution of authorship trends in the field of Neuroscience. We conducted our analysis based on a dataset containing 580,782 neuroscience publications produced from 2000 to 2022, focusing on the publications within the Group of ten (G10) countries. Using a matrix-based methodology, we extracted and analyzed the average number of authors per country. Our findings reveal a consistent rise in authorship across all G10 countries over the past two decades. Italy emerged with the highest average number of authors, while France stood out for experiencing the most significant increase, particularly in the last decade. The countries with the lowest number of authors per publication were the USA, UK and Canada. Differences between countries could result from variations in the size of collaboration between researchers in different countries. Additionally, these differences may depend on utilitarian considerations aimed at receiving higher scores in the individual evaluation of their own work. We propose that a normalization procedure for the number of authors should be implemented to ensure a fair evaluation of researchers.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 52-57"},"PeriodicalIF":1.5,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000563/pdfft?md5=c945153f3bc86ec009bc60a7972a3b1d&pid=1-s2.0-S2667242124000563-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of Parkinson's disease therapy with plant extracts and nutrition’s evolving roles","authors":"Patrick Oluwole Abolarin ,&nbsp;Abdulbasit Amin ,&nbsp;Abdulrazaq Bidemi Nafiu ,&nbsp;Olalekan Michael Ogundele ,&nbsp;Bamidele Victor Owoyele","doi":"10.1016/j.ibneur.2024.05.011","DOIUrl":"10.1016/j.ibneur.2024.05.011","url":null,"abstract":"<div><p>Parkinson’s disease (PD) is a neurodegenerative disease characterized by death of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Death of dopaminergic cells in the SNpc leads to manifestations of motor dysfunction and non-motor symptoms of PD. The progression of PD symptoms severely affects the quality of life of patients and poses socio-economic problems to families and society at large. The clinical and neuropathological characteristics of PD are triggered by multiple factors such as oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein aggregation. Notwithstanding the advancements in pharmacological therapy in PD management, there is burgeoning interest in alternative and complementary approaches, essentially nutrition and plant extracts strategies. This review gives widespread analysis of the role of nutrition and plant extracts in the management of PD. Studies that investigated the effects of various dietary compounds and plant extract on PD symptoms and progression were reviewed from existing literatures. Nutraceuticals, including vitamins and phytochemicals such as <em>Mucuna pruriens</em> have shown potential neuroprotective functions in preclinical and clinical studies. Indeed, these strategies ameliorate mitochondrial dysfunction, oxidative stress, and neuroinflammation, all which are implicated in the pathogenesis of PD. The neuroprotective mechanisms of nutrition and plant extracts in PD, with emphasis on their capacity to target multiple pathways implicated in PD are discussed. Additionally, challenges and limitations related with translating preclinical findings into clinical practice including standardization of dosing regimens, bioavailability, and inter-individual variability are discussed. Largely, this review elucidates on the role of nutrition and plant extracts as adjunctive therapy in PD management.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 1-12"},"PeriodicalIF":1.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266724212400054X/pdfft?md5=c8da804237eb0e66d7e8029a1087563b&pid=1-s2.0-S266724212400054X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141142172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene expression in the dorsal root ganglion and the cerebrospinal fluid metabolome in polyneuropathy and opioid tolerance in rats","authors":"Fredrik H.G. Ahlström ,&nbsp;Hanna Viisanen ,&nbsp;Leena Karhinen ,&nbsp;Vidya Velagapudi ,&nbsp;Kim J. Blomqvist ,&nbsp;Tuomas O. Lilius ,&nbsp;Pekka V. Rauhala ,&nbsp;Eija A. Kalso","doi":"10.1016/j.ibneur.2024.05.006","DOIUrl":"10.1016/j.ibneur.2024.05.006","url":null,"abstract":"<div><p>First-line pharmacotherapy for peripheral neuropathic pain (NP) of diverse pathophysiology consists of antidepressants and gabapentinoids, but only a minority achieve sufficient analgesia with these drugs. Opioids are considered third-line analgesics in NP due to potential severe and unpredictable adverse effects in long-term use. Also, opioid tolerance and NP may have shared mechanisms, raising further concerns about opioid use in NP. We set out to further elucidate possible shared and separate mechanisms after chronic morphine treatment and oxaliplatin-induced and diabetic polyneuropathies, and to identify potential diagnostic markers and therapeutic targets. We analysed thermal nociceptive behaviour, the transcriptome of dorsal root ganglia (DRG) and the metabolome of cerebrospinal fluid (CSF) in these three conditions, in rats. Several genes were differentially expressed, most following oxaliplatin and least after chronic morphine treatment, compared with saline-treated rats. A few genes were differentially expressed in the DRGs in all three models (e.g. <em>Csf3r</em> and <em>Fkbp5</em>). Some, e.g. <em>Alox15 and Slc12a5,</em> were differentially expressed in both diabetic and oxaliplatin models. Other differentially expressed genes were associated with nociception, inflammation, and glial cells. The CSF metabolome was most significantly affected in the diabetic rats. Interestingly, we saw changes in nicotinamide metabolism, which has been associated with opioid addiction and withdrawal, in the CSF of morphine-tolerant rats. Our results offer new hypotheses for the pathophysiology and treatment of NP and opioid tolerance. In particular, the role of nicotinamide metabolism in opioid addiction deserves further study.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 38-51"},"PeriodicalIF":1.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000484/pdfft?md5=6d2f2006283ccf65c3782b75d41069d0&pid=1-s2.0-S2667242124000484-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141142531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of implicit motor learning with consecutive exposure to visual errors","authors":"Naoyoshi Matsuda ,&nbsp;Masaki O. Abe","doi":"10.1016/j.ibneur.2024.05.004","DOIUrl":"10.1016/j.ibneur.2024.05.004","url":null,"abstract":"<div><p>Visual errors induced by movement drive implicit corrections of that movement. When similar errors are experienced consecutively, does sensitivity to the error remain consistent each time? This study aimed to investigate the modulation of implicit error sensitivity through continuous exposure to the same errors. In the reaching task using visual error-clamp feedback, participants were presented with the same error in direction and magnitude for four consecutive trials. We found that implicit error sensitivity decreased after exposure to the second error. These results indicate that when visual errors occur consecutively, the sensorimotor system exhibits different responses, even for identical errors. The continuity of errors may be a factor that modulates error sensitivity.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 32-37"},"PeriodicalIF":1.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000496/pdfft?md5=95b75eebb576f9286650f8f17aeaff52&pid=1-s2.0-S2667242124000496-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effect of triptolide on neuronal inflammation in rats with mild brain injury","authors":"Zhanglu Fang ,&nbsp;Guanghong Shen ,&nbsp;Chengjian Lou ,&nbsp;Benson O.A. Botchway ,&nbsp;Qinglin Lu ,&nbsp;Qining Yang ,&nbsp;Nashwa Amin","doi":"10.1016/j.ibneur.2024.05.007","DOIUrl":"10.1016/j.ibneur.2024.05.007","url":null,"abstract":"<div><p>Concussions sustained while playing sports are a prominent cause of mild traumatic brain injury (mTBI), which is prevalent among teenagers. The early and intermediate stages of mild traumatic brain injury (mTBI) can be characterized by inflammation, neurodegeneration, and brain tissue edema, which can lead to permanent brain damage.</p><p>The present study investigated the therapeutic effects of triptolide in mTBI and brain damage recovery. After building mTBI model in male rat, triptolide administrated daily for 1 week in the treated group. On day 3 and day 7 of administration, hippocampus tissues were collected to evaluate inflammation and autophagy in the brain. The expressions of inflammatory factors interleukin (IL)-1β and tumor necrosis factor-alpha in serum were downregulated, while IL-10 expression was upregulated when compared with the mTBI group on day 3 and day 7. The expression of IL-10 on day 7 was higher than on day 3. Quantitative polymerase chain reaction (qPCR) analysis of inflammatory-related factors (i.e., <em>Il-1β</em> and nuclear factor-κB (<em>Nf-κb</em>), and western blot as well as immunofluorescence staining of autophagy-related proteins (i.e., LC3B) and aquaporin (AQP 4) showed lower expression on day 3 and day 7 in the triptolide-treated group. Moreover, NeuN immunostaining, and hematoxylin and eosin (HE) staining for hippocampus region revealed that the triptolide-treated group showed a decrease in damaged cells. Our findings emphasize the effectiveness of triptolide therapy after mild traumatic brain injury via modulating autophagy, attenuating inflammation and reduces edema by decreasing AQP 4 expression.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 13-21"},"PeriodicalIF":1.5,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000514/pdfft?md5=500d812c31c058c7dc67a7709202ec39&pid=1-s2.0-S2667242124000514-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141139425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLUT2 regulation of p38 MAPK isoform protein expression and p38 phosphorylation in male versus female rat hypothalamic primary astrocyte Cultures","authors":"Madhu Babu Pasula,&nbsp;Paul W. Sylvester,&nbsp;Karen P. Briski","doi":"10.1016/j.ibneur.2024.05.008","DOIUrl":"https://doi.org/10.1016/j.ibneur.2024.05.008","url":null,"abstract":"<div><p>Recent studies documented regulation of hypothalamic astrocyte mitogen-activated protein kinase (MAPK) pathways, including p38, by the plasma membrane glucose carrier/sensor glucose transporter-2 (GLUT2). Sex-specific GLUT2 control of p38 phosphorylation was observed, but effects on individual p38 family protein profiles were not investigated. Current research employed an established primary astrocyte culture model, gene knockdown tools, and selective primary antisera against p38-alpha, p38-beta, p38-gamma, and p38-delta isoforms to investigate whether GLUT2 governs expression of one or more of these variants in a glucose-dependent manner. Data show that GLUT2 inhibits baseline expression of each p38 protein in male cultures, yet stimulates p38-delta profiles without affecting other p38 proteins in female. Glucose starvation caused selective up-regulation of p38-delta profiles in male versus p38-alpha and -gamma proteins in female; these positive responses were amplified by GLUT2 siRNA pretreatment. GLUT2 opposes or enhances basal p38 phosphorylation in male versus female, respectively. GLUT2 siRNA pretreatment did not affect glucoprivic patterns of phospho-p38 protein expression in either sex. Outcomes document co-expression of the four principal p38 MAPK family proteins in hypothalamic astrocytes, and implicate GLUT2 in regulation of all (male) versus one (female) variant(s). Glucoprivation up-regulated expression of distinctive p38 isoforms in each sex; these stimulatory responses are evidently blunted by GLUT2. Glucoprivic-associated loss of GLUT2 gene silencing effects on p38 phosphorylation infers either that glucose status determines whether this sensor controls phosphorylation, or that decrements in screened glucose in each instance are of sufficient magnitude to abolish GLUT2 regulation of that function.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"16 ","pages":"Pages 635-642"},"PeriodicalIF":1.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000538/pdfft?md5=ab8fcd18d1e11b1431501666b3817168&pid=1-s2.0-S2667242124000538-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of intrahippocampal microinjection of VU0155041, a positive allosteric modulator of mGluR4, on long term potentiation in a valproic acid-induced autistic male rat model","authors":"Zahra Ebrahimi ,&nbsp;Parsa Gholipour ,&nbsp;Reihaneh Mohammadkhani ,&nbsp;Reza Ghahremani ,&nbsp;Abdolrahman Sarihi ,&nbsp;Alireza Komaki ,&nbsp;Iraj Salehi ,&nbsp;Seyed Asaad Karimi","doi":"10.1016/j.ibneur.2024.05.005","DOIUrl":"https://doi.org/10.1016/j.ibneur.2024.05.005","url":null,"abstract":"<div><p>The precise cause of autism spectrum disorder (ASD) is not fully understood. Despite the involvement of glutamatergic dysregulation in autism, the specific contribution of mGlu4 receptors to synaptic plasticity remains unclear. Using the positive allosteric modulator VU0155041, we aimed to restore long-term potentiation (LTP) in the perforant path-dentate gyrus (PP-DG) pathway in VPA-induced autistic rat model. High-frequency stimulation was applied to the PP-DG synapse to induce LTP, while the VU0155041 was administered into the DG. Unexpectedly, VU0155041 failed to alleviate the observed LTP reduction in VPA-exposed rats, further resulting in a significant decrease in population spike LTP. This unexpected outcome prompts discussion on the complex nature of mGlu4 receptor modulation, highlighting potential interference with physiological processes underlying synaptic plasticity.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"16 ","pages":"Pages 629-634"},"PeriodicalIF":1.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000502/pdfft?md5=52e9e71ff0c5c6d6687ddfc23f3f6062&pid=1-s2.0-S2667242124000502-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of chronic administration of ostruthin on depression-like behavior in chronically stressed mice","authors":"Masayoshi Okada ,&nbsp;Thi Thu Thuy Tran","doi":"10.1016/j.ibneur.2024.05.009","DOIUrl":"https://doi.org/10.1016/j.ibneur.2024.05.009","url":null,"abstract":"<div><p>We have previously shown that a single dose of a TREK-1 channel activator, ostruthin, exhibited antidepressant and anxiolytic effects in acute behavioral test models in mice. To assess the potential clinical application, it is essential to evaluate the effects of long-term administration of ostruthin in a chronically stressed mouse model, which is considered to be similar to the clinical condition of major depression in humans. Here, we tested the effects of a single and a 7-day administration of ostruthin on mice that were subjected to chronic unpredictable mild stress (CUMS). A single administration of ostruthin showed antidepressive effects in the tail suspension and forced swim tests of CUMS-treated mice. Unexpectedly, the 7-day administration exhibited only insignificant antidepressive and anxiolytic effects. The 7-day regimen did not affect food intake or body-weight gain, suggesting the absence of apparent cytotoxicity. The mice receiving the 7-day administration had significantly lower blood concentrations of ostruthin compared to those receiving a single dose, suggesting an upregulation of drug-metabolizing activities. These findings suggest that there is a need for stable TREK-1 channel activators that are not affected by drug metabolism.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"16 ","pages":"Pages 622-628"},"PeriodicalIF":1.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000526/pdfft?md5=3fdb3efea334e5d53b3f721fd3411e08&pid=1-s2.0-S2667242124000526-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}