Neuroscience Letters最新文献

{"title":"Microinjection of brain-derived neurotrophic factor into the dorsal hippocampus alleviates cognitive dysfunction and increases hippocampal cell proliferation in olfactory bulbectomized mice","authors":"Jinichi Isono ,&nbsp;Osamu Nakagawasai ,&nbsp;Kohei Takahashi ,&nbsp;Wataru Nemoto ,&nbsp;Koichi Tan-No","doi":"10.1016/j.neulet.2025.138257","DOIUrl":"10.1016/j.neulet.2025.138257","url":null,"abstract":"<div><div>Patients with depression show cognitive dysfunction and experience decreased motivation, which interfere with their daily lives. However, whether brain-derived neurotrophic factor (BDNF) in the dorsal hippocampus is involved in depression-associated cognitive deficits is unclear. In this study, olfactory bulbectomized mice, used as a model of depression, showed cognitive dysfunction in the Y-maze and passive avoidance tests and reduction of cell proliferation in the hippocampal dentate gyrus. Microinjection of BDNF into the dorsal hippocampus alleviated the cognitive dysfunction induced by the olfactory bulbectomy and increased hippocampal cell proliferation. This study suggests that BDNF injection in the dorsal hippocampus modulates cognitive functions with cell proliferation in the hippocampal dentate gyrus, thus supporting the importance of hippocampal BDNF in cognitive impairment accompanying depression.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138257"},"PeriodicalIF":2.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-high dilution medicines can modulate dopaminergic molecular targets and ΔFosB in the Nucleus accumbens preventing morphine reacquisition in rats","authors":"Murilo Barboza Fontoura ,&nbsp;Jessica Leandra Oliveira da Rosa ,&nbsp;Domenika Rubert Rossato ,&nbsp;Leana Eduarda Mezzomo de Souza ,&nbsp;Mustafa Munir Mustafa Dahleh ,&nbsp;Marina Prigol ,&nbsp;Gustavo Petri Guerra ,&nbsp;Hecson Jesser Segat ,&nbsp;Marilise Escobar Burger","doi":"10.1016/j.neulet.2025.138256","DOIUrl":"10.1016/j.neulet.2025.138256","url":null,"abstract":"<div><div>Addiction is a recurring disease that constitutes a significant public health issue, particularly evident in the global opioid crisis involving substances like morphine (MORPH). Reestablishing to opioid use poses a major obstacle to successful detoxification treatment, as many individuals return to drug use after withdrawal. Therefore, given that drug addiction involves emotional, social, and physical factors, there is a necessity to explore integrative medicine approaches, including ultra-high dilution medicines such as isotherapic (ISO) and organotherapic (ORG) treatments. This integrative approach holds promising potential in addressing drug addiction, as frequent reinstatement to addictive substances entail comprehensive symptoms. In our study following the MORPH conditioned place preference (CPP) paradigm, rats were treated with ISO or ORG for 14 days during MORPH-CPP extinction and subsequently challenged with the drug to assess MORPH-CPP reacquisition. The findings confirmed the hedonic effects of MORPH in the CPP, which also increased D1- and D3-R, DAT, and ΔFosB immunoreactivity in the <em>Nucleus accumbens</em> (NAc). Conversely, both ISO and ORG prevented MORPH-CPP reestablishing, whereas ORG treatment was associated with increased D2- and decreased D3-R levels. Both ORG and ISO increased DAT levels and decreased D1-R and ΔFosB, thus restoring the molecular neuromodulation induced by MORPH. To our knowledge, this study represents the first demonstration of the beneficial influence of ultra-high dilution medicines as a promising treatment for opioid use disorder. This finding is particularly relevant as these medicines are not associated with toxicity or undesirable side effects. Clinical studies are warranted to validate their efficacy in rehabilitation centers for drug use disorder.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138256"},"PeriodicalIF":2.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of repetition and estrous cycle on behavioral tests in female ICR mice","authors":"Michiyo Maruyama","doi":"10.1016/j.neulet.2025.138253","DOIUrl":"10.1016/j.neulet.2025.138253","url":null,"abstract":"<div><div>The open field test (OF) and elevated plus maze test (EPM) are widely used behavioral assessment methods for evaluating anxiety-like behaviors in rodents based on their spontaneous activity. These tests are commonly used to screen anxiolytic compounds. Repeated trials are often required to assess the efficacy of pharmacological treatments. Previous studies suggested that the number of experimental trials can influence various parameters in male animals. However, the knowledge of the effects of repeated trials on female mice is limited. Here, I report the effects of repeated testing on behavioral parameters in female ICR mice during the OF and EPM. The results showed that the number of trial repetitions influenced several behavioral parameters, consistent with previous findings in males. In contrast, the female-specific estrous cycle had a smaller effect. Overall, this study provides valuable insights for designing behavioral experiments involving female animals.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138253"},"PeriodicalIF":2.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal exercise during pregnancy: Sex-specific impacts on offspring memory and maternal deprivation effects","authors":"Guilherme Salgado Carrazoni,&nbsp;Pâmela B. Mello-Carpes","doi":"10.1016/j.neulet.2025.138252","DOIUrl":"10.1016/j.neulet.2025.138252","url":null,"abstract":"<div><div>Maternal deprivation (MD) is a well-established paradigm used to study the effects of early-life stress on offspring brain development and behavior, particularly memory. Maternal exercise (ME) during pregnancy has been shown to influence offspring brain development and behavior. Our study examined whether ME protocols—stop, start, reduce, or maintain running during pregnancy—could protect offspring from MD-induced memory deficits and impact hippocampal oxidative balance. Initially, adult Wistar female rats were divided into five groups: non-exercised mothers (NE), mothers who exercised only before pregnancy (PRE), mothers who exercised before and reduced the intensity during pregnancy (RED), mothers who exercised at the same intensity before and during pregnancy (EQUAL), and mothers who started exercise during pregnancy (GEST). After delivery, the groups were subdivided into control (CT) and MD. At 90 days of age, the offspring underwent an object recognition (OR) memory test, and hippocampal lipid peroxidation and catalase (CAT) levels were measured. MD-induced memory deficits in male but not female offspring. Only the male PRE group showed a memory deficit, while all other exercise protocols prevented the MD-induced deficits. MD did not affect hippocampal cell membrane peroxidation, and PRE and EQUAL protocols increased catalase levels compared to NE + CT controls. Our results highlight that maintaining or starting exercise during pregnancy mitigates memory deficits induced by MD, particularly in male offspring.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138252"},"PeriodicalIF":2.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Over-expression of α-synuclein 98 triggers intracellular oxidative stress and enhances susceptibility to rotenone” [Neurosci. Lett. 491 (2011) 148–152]","authors":"Kai-Li Ma,&nbsp;Yu-He Yuan,&nbsp;Lian-Kun Song,&nbsp;Ning Han,&nbsp;Nai-Hong Chen","doi":"10.1016/j.neulet.2025.138238","DOIUrl":"10.1016/j.neulet.2025.138238","url":null,"abstract":"","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138238"},"PeriodicalIF":2.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal expression of Nischarin in developing rat brain mediates neuronal migration via the PAK1/LIMK1/cofilin pathway","authors":"Ruyi Zhang ,&nbsp;Hangdi Chen ,&nbsp;Kai Guo ,&nbsp;Zhihao Bai ,&nbsp;Jie Huang ,&nbsp;Xiong Zhang ,&nbsp;Yuemin Ding","doi":"10.1016/j.neulet.2025.138251","DOIUrl":"10.1016/j.neulet.2025.138251","url":null,"abstract":"<div><div>Nischarin, a cytoplasmic scaffold protein, plays a crucial role in modulating cell morphology and function. Our prior investigations revealed its high expression in certain areas of the adult rat brain. Yet, the intricate spatiotemporal dynamics of Nischarin expression across various stages of rat development, as well as its influence on the nervous system’s functionality, remain unexplored. In this study, we meticulously examined the expression patterns of Nischarin and the phosphorylation profiles of the PAK1/LIMK1/cofilin signaling cascade within the cerebral cortex and hippocampus, spanning from embryonic development through postnatal maturation. Furthermore, we delved into how Nischarin affects the neuronal migration and the underlying mechanisms. Our findings indicated that from postnatal day 1 to 28, there was a consistent increasing trend in both the protein and mRNA levels of Nischarin in the cerebral cortex and hippocampus. Interestingly, the phosphorylation levels of PAK1 and LIMK1 increased briefly at postnatal day 1, and then gradually decreased from postnatal day 21 to 28. Immunocoprecipitation revealed the interaction between endogenous Nischarin and PAK1/LIMK1 in the cerebral cortex. Notably, suppressing Nischarin expression markedly bolstered the migration ability of Neuro-2a cells and concurrently elevated the phosphorylation levels of the PAK1/LIMK1/cofilin signaling pathway. This elevation was effectively counteracted by the PAK1 inhibitor IPA3. Our research suggests that the progressive increase in Nischarin protein expression during development is likely integral to the normal developmental trajectory of the rat brain. This involvement appears to be mediated by Nischarin’s regulation of neuronal migration through modulating the activity of the PAK1/LIMK1/cofilin signaling pathway.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138251"},"PeriodicalIF":2.5,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium exacerbates Lafora body formation in the Epm2a-/- Lafora disease mouse model","authors":"Jun Wu,&nbsp;Tori C. Lynn ,&nbsp;Silvia Nitschke,&nbsp;Sharmistha Mitra,&nbsp;Berge A. Minassian","doi":"10.1016/j.neulet.2025.138250","DOIUrl":"10.1016/j.neulet.2025.138250","url":null,"abstract":"<div><div>Lafora disease (LD) is a fatal neurodegenerative epilepsy of teenagers due to accumulations of overlong-branched glycogen (Lafora bodies, LBs) and caused by deficient laforin or its interacting partner malin. While how the laforin-malin complex regulates glycogen chain lengths is unknown, it is known that downregulating the glycogen chain-elongating enzyme glycogen synthase prevents LB formation. Lithium is a longstanding treatment for neuropsychiatric diseases. Lithium was recently shown to lead to glycogen synthase phosphorylation (i.e. inhibition) in rat brains through an unknown pathway. We tested whether lithium can prevent LB formation in laforin-deficient LD mice. We found that in these mice lithium leads to glycogen synthase dephosphorylation (i.e. activation), and increased LBs in hearts of 100% and brains of 40% of treated mice. The latter were all sickly compared to the 60% in whose brains LBs did not increase. These results are generally cautionary regarding therapeutic translatability from rodents to humans where basic mechanisms are unknown. Increased LB formation only in frail mice suggests existence of self-perpetuating processes in LD. Finally, lithium clearly influences glycogen metabolism with outcomes similar to disturbances of the laforin-malin complex. Understanding lithium’s action in glycogen metabolism may aid the understanding of the mechanisms of laforin-malin and LD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138250"},"PeriodicalIF":2.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced flavoprotein autofluorescence imaging in rats using a combination of thin skull window and skull-clearing reagents","authors":"Yuto Ogawa ,&nbsp;Kazuaki Nagasaka ,&nbsp;Daisuke Ishii ,&nbsp;Ayane Nagao ,&nbsp;Hitomi Ikarashi ,&nbsp;Naofumi Otsuru ,&nbsp;Hideaki Onishi","doi":"10.1016/j.neulet.2025.138239","DOIUrl":"10.1016/j.neulet.2025.138239","url":null,"abstract":"<div><div>Flavoprotein autofluorescence (FA) imaging is a powerful technique for investigating neural activity in vivo. However, its application in rats is limited by the thickness of the intact skull, which reduces light transmission and signal-to-noise ratio (SNR). In this study, we introduce a novel approach that integrates a thin skull window (TSW) with a skull-clearing reagent (CTSW) to enhance FA imaging in rats. The FA signals evoked by somatosensory stimulation were recorded under both TSW and CTSW conditions. The results demonstrate that CTSW significantly improved the SNR of FA signals compared to TSW alone, enabling more precise detection of neural activity. Notably, the enhanced signal clarity facilitated robust imaging in the secondary motor cortex (M2), a region where activity is barely detectable using conventional TSW. By better preserving intracranial physiological conditions than craniotomy, CTSW minimizes postoperative complications and supports longitudinal imaging. Furthermore, this technique may be applicable to other optical imaging modalities, including calcium and vascular imaging. The ability to enhance cortical signal detection while maintaining a minimally invasive preparation positions CTSW as a promising tool for functional mapping and long-term studies in behaving rats.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138239"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the effect of biperiden (cholinergic muscarinic receptor antagonist) on ethanol self-administration in rats","authors":"Paola Palombo ,&nbsp;Clarice Ribeiro Lira ,&nbsp;Sara Emi Matos Mendes Ferreira Badaro ,&nbsp;Lucas Teodoro ,&nbsp;Fábio Cardoso Cruz ,&nbsp;José Carlos Fernandes Galduróz ,&nbsp;Rodrigo Molini Leão","doi":"10.1016/j.neulet.2025.138240","DOIUrl":"10.1016/j.neulet.2025.138240","url":null,"abstract":"<div><div>Evidence from the literature suggests that alcohol use disorder (AUD) is closely associated with alterations in neuronal plasticity and the memory system, related to modifications in muscarinic receptors. The present study aimed to investigate the effects of systemic injection of biperiden, a muscarinic cholinergic antagonist, in experimental protocols of progressive ratio, 24-hour binge alcohol consumption, and reinstatement of context-induced ethanol self-administration. The results demonstrated that biperiden at doses of 5 and 10 mg/kg (i.p.) effectively reduced the animals’ motivation for alcohol consumption, as evidenced by decreased responses on the active lever and a reduction in the last ratio achieved in the progressive ratio protocol. Furthermore, these same doses significantly reduced ethanol consumption in the 24-hour binge protocol. Treatment with biperiden at doses of 1, 5, and 10 mg/kg also attenuated alcohol-seeking behavior after re-exposure to the context associated with ethanol self-administration. These findings suggest that biperiden may have therapeutic potential in the treatment of alcohol use disorder, indicating that modulation of the cholinergic system could be a promising avenue for further investigation.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138240"},"PeriodicalIF":2.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRMP2 and its phosphorylation prevent axonal misrouting of the corticospinal tract","authors":"Satohiro Takizawa ,&nbsp;Yurika Nakanishi ,&nbsp;Yumeno Koga ,&nbsp;Yuki Yamazaki ,&nbsp;Papachan Kolattukudy ,&nbsp;Yoshio Goshima ,&nbsp;Toshio Ohshima","doi":"10.1016/j.neulet.2025.138231","DOIUrl":"10.1016/j.neulet.2025.138231","url":null,"abstract":"<div><div>During the development of the central nervous system (CNS), the formation of neural circuits such as the corticospinal tract (CST) is crucial to control voluntary movement and is regulated by axonal guidance mechanisms.</div><div>In this study, we examined the role of CRMP2 (Collapsin response mediator protein 2) in the formation of CST. CRMP2, which binds to actin and microtubules to control the cytoskeleton, is a phosphoprotein whose activity depends on its phosphorylated state. To inhibit Cyclin-dependent kinase 5 (Cdk5) phosphorylation, CRMP2 knock-in (<em>crmp2^ki/ki</em>) mice were generated in which the serine residue at position 522 was replaced with alanine. Our results showed that both CRMP2 knock-out (<em>crmp2^-/-</em>) and <em>crmp2^ki/ki</em> mice exhibited higher percentages of CST axons that crossed the midline erroneously than wild-type (WT) mice. However, in mice lacking CRMP1, which is highly homologous to CRMP2, few axons crossed the midline, similar to WT mice. Additionally, <em>crmp2^-/-</em> and <em>crmp2^ki/ki</em> mice showed decreased proportions of independent forelimb movements. These findings emphasize that CRMP2 and its phosphorylation are necessary for proper CST formation in the mouse CNS.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138231"},"PeriodicalIF":2.5,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}