Neurotoxicity Research最新文献

{"title":"Exploring the potential role of microtubule associated proteins-2 in the pathogenesis of HIV associated neurocognitive disorders.","authors":"Melanie K Becher, Valeria Avdoshina, Lee A Campbell, Italo Mocchetti","doi":"10.1007/s12640-025-00739-1","DOIUrl":"10.1007/s12640-025-00739-1","url":null,"abstract":"<p><p>HIV-associated neurocognitive disorder (HAND) persists in people living with HIV (PLWH) despite antiretroviral therapy. HAND is characterized by synapto-dendritic damage, yet the cause of this pathology is still under investigation. Various viral proteins, including the envelope protein gp120, have been proposed to be the leading neurotoxic agents underlying HIV-mediated neuronal degeneration. Gp120 has been shown to bind to neuronal microtubules (MTs) and impair their functions. The dynamic properties of MTs are modulated by microtubule-associated proteins (MAP), including MAP2, which is particularly abundant in dendrites. This review article explores how gp120 could be altering the function of the neuronal cytoskeleton by affecting MAP2. These effects may serve as a causal link between viral proteins and HAND pathology.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"19"},"PeriodicalIF":2.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kynurenine Pathway in Epilepsy: Unraveling Its Role in Glutamate Excitotoxicity, GABAergic Dysregulation, Neuroinflammation, and Mitochondrial Dysfunction.","authors":"Manpreet Kaur, Pratyush Porel, Royal Patel, Khadga Raj Aran","doi":"10.1007/s12640-025-00738-2","DOIUrl":"10.1007/s12640-025-00738-2","url":null,"abstract":"<p><p>Epilepsy is a chronic noncommunicable neurological disorder characterized by recurrent seizures and ranks as the seventh most prevalent neurological disease globally. According to the Global Burden of Disease report, 3.40 billion people were affected by epilepsy in 2021. The pathophysiology of epilepsy states that a disturbed balance between excitatory and inhibitory signaling at the synaptic level, which can cause seizure activity, is similar across epilepsies and includes mitochondrial dysfunction, neuroinflammation, and kynurenine metabolites such as kynurenic acid and quinolinic acid. The kynurenine pathway (KP) is the major metabolic pathway in which tryptophan (TRP) is the key precursor which is further converted into a variety of neuroactive substances that can have both neurotoxic metabolites (Quinolinic acid) and neuroprotective metabolites such as kynurenic acid, and picolinic acid. KP plays a significant role in the brain such as the metabolism of TRP, the production of metabolites, and its impact on aging. However, higher concentrations of kynurenine and its metabolites, such as quinolinic acid may increase the frequency and intensity of seizures, and dysregulation of the KP has been linked to the pathophysiology of epilepsy. Concurrently, glutamate and GABA signaling is altered by neuroinflammatory processes linked to epilepsy, which results in excitotoxic neuronal damage. This review aims to provide novel therapeutic strategies that might improve the prognosis of individuals with epilepsy and related disorders by elucidating the mechanisms underlying KP dysregulation in these circumstances. To develop targeted therapies for CNS disorders characterized by inflammation and seizures, it is essential to understand how kynurenine metabolites both promote and prevent excitotoxicity.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"18"},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Analysis of Decabromodiphenyl Ether-Induced Neurotoxicity in Humans Using Network Toxicology and Molecular Docking.","authors":"Fuat Karakuş, Burak Kuzu","doi":"10.1007/s12640-025-00741-7","DOIUrl":"10.1007/s12640-025-00741-7","url":null,"abstract":"<p><p>Commercial decabromodiphenyl ether (c-decaBDE) is a widely used additive flame retardant in textiles and plastics. This formulation predominantly consists of the congener BDE-209, with trace amounts of other brominated diphenyl ether congeners, such as nonabromodiphenyl ether and octabromodiphenyl ether. Recognized as a persistent organic pollutant due to its potential for long-range environmental transport, c-decaBDE poses significant environmental threats and serious human health risks, including endocrine, reproductive, developmental, and neurotoxic effects. The mechanisms underlying its neurotoxicity remain largely undefined. This study investigates the neurotoxic effects of BDE-209 in humans through network toxicology, multi-level bioinformatics approaches, and molecular docking analyses. Prediction results indicate that BDE-209 can cross the blood-brain barrier, entering the central nervous system and inducing neurotoxic effects. A comprehensive analysis has identified 294 potential targets linked to the neurotoxicity induced by BDE-209. Gene-gene interaction and pathway enrichment analyses revealed significant associations related to cellular responses to chemical stress and synaptic transmission. Further investigation of protein-protein interactions, combined with centrality analysis, identified 14 hub targets, including CaMK-II alpha, PSD-95, GluR-1, and GluN2B, as key proteins in this process. Molecular docking results indicate that BDE-209 exhibits a stronger binding affinity to GluN2B, a subunit of the N-methyl-D-aspartate (NMDA) receptors, compared to other key targets. These findings suggest that BDE-209 may disrupt the function of GluN2B-containing NMDA receptors, potentially leading to their inhibition. Such inhibition could result in reduced excitatory neurotransmission, impairing synaptic potentiation and plasticity, and ultimately contributing to neurotoxicity.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"17"},"PeriodicalIF":2.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxytetracycline and its Non-Antibiotic Derivative DOT Protect Midbrain Dopamine Neurons from Iron-Driven Oxidative Damage.","authors":"Thaís Antonia Alves Fernandes, Aurore Tourville, Ismaila Ciss, Rafaela Ribeiro Silva, Bianca Andretto de Mattos, Maurício Dos Santos Pereira, Maxime Oblaza, Jean-Michel Brunel, Laurent Ferrié, Rita Raisman-Vozari, Bruno Figadère, Elaine Del-Bel, Patrick Pierre Michel","doi":"10.1007/s12640-025-00742-6","DOIUrl":"10.1007/s12640-025-00742-6","url":null,"abstract":"<p><p>This study aimed to investigate the neuroprotective potential of the tetracycline (TC) antibiotic oxytetracycline (OT) and its non-antibiotic derivative 4-dedimethylamino 12a-deoxy-oxytetracycline (DOT), in experimental conditions that mimic the gradual loss of dopamine (DA) neurons in Parkinson's disease (PD). Specifically, we established a model system of mouse midbrain cultures where DA neurons progressively die when exposed to an iron-containing medium. We found that OT (EC₅₀ = 0.25µM) and DOT (EC₅₀ = 0.34µM) efficiently protected DA neurons from degeneration, with these effects observable until advanced stages of neurodegeneration. The reference antibiotic TC doxycycline (DOX) also exhibited protective effects in this context. Importantly, DA neurons rescued by OT, DOT, and DOX retained their capacity to accumulate and release DA, indicating full functional integrity. Additionally, molecules with iron-chelating properties (apotransferrin, desferoxamine), as well as inhibitors of lipid peroxidation and ferroptosis (Trolox, Liproxstatin-1), could replicate the rescue of DA neurons provided by OT, DOT, and DOX. Live-cell imaging studies showed that test TCs and other neuroprotective molecules prevented the emission of intracellular reactive oxygen species and the associated disruption of the mitochondrial membrane potential. However, neither OT, DOT, nor DOX could protect DA neurons from selective mitochondrial poisoning by 1-methyl-4-phenylpyridinium. This suggests that test TCs may be protective against iron-mediated damage through a mechanism not directly involving mitochondria. Overall, we demonstrate that OT and DOT possess promising properties that could be useful for combating PD neurodegeneration. However, the absence of antimicrobial activity makes DOT a better candidate drug compared to its parent compound OT.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"16"},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effect of myo-Inositol Against Decitabine-Induced Neural Tube Defects in Embryonic Zebrafish.","authors":"Venugopalan Rajesh, Subramani Karthi, Manni Venkatachari Kumudhavalli","doi":"10.1007/s12640-025-00735-5","DOIUrl":"10.1007/s12640-025-00735-5","url":null,"abstract":"<p><p>Neural tube defects (NTDs) are severe congenital anomalies affecting 1-2 infants per 1000 births, and are influenced by genetic and environmental factors, with DNA hypomethylation and methylation cycle suppression being key causes. In our earlier investigation, decitabine (DCT) caused multiple NTDs in embryonic zebrafish, supporting this hypothesis. Recent research has emphasized the importance of myo-inositol (MI) in embryonic development and its efficacy in reducing the risk of neural tube defects, even in cases resistant to folate. We aimed to examine the effect of MI on DCT-induced NTDs in an embryonic zebrafish model. The embryos were exposed to 1 mM DCT alone, 50 µM MI with 1 mM DCT, 100 µM MI with 1 mM DCT, and a control group for comparison. The development, hatching, mortality rates, neural tube malformations, and neural tube patterning of developing embryos were monitored and recorded. Exposure to MI significantly reduced the incidence of NTDs in developing embryos. At concentrations of 50 µM and 100 µM, MI provided 35% and 30% protection against DCT-induced neural tube malformation, respectively. Multiple NTDs were significantly reduced in the MI groups, with 1 mM DCT causing 95% defects, 50 µM MI with 1 mM DCT causing 50%, and 100 µM MI with 1 mM DCT causing 55% defects. The DCT-induced hatching delay was also reversed by MI treatment. Alizarin red staining and histopathological observations supported these observations. In the context of neural tube development, the protective effects of MI against DCT-induced NTDs could be attributed to its potential role in epigenetic regulation, which may influence genetic expression.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"14"},"PeriodicalIF":2.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin Protects Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons from Oxidative Damage Through Antioxidant Mechanisms.","authors":"Mohammad H Gharandouq, Mohammad A Ismail, Tareq Saleh, Malik Zihlif, Nidaa A Ababneh","doi":"10.1007/s12640-025-00734-6","DOIUrl":"10.1007/s12640-025-00734-6","url":null,"abstract":"<p><p>The antidiabetic drug metformin possesses antioxidant and cell protective effects including in neuronal cells, suggesting its potential use for treating neurodegenerative diseases. This study aimed to assess metformin's effects on viability and antioxidant activity in human-induced pluripotent stem cell (hiPSC)-derived neurons under varying concentrations and stress conditions. Six lines of hiPSC-derived neuronal progenitors derived from healthy human iPSCs were treated with metformin (1-500 µM) on day 18 of differentiation. For mature neurons (day 30), three concentrations (10 µM, 50 µM, and 100 µM) were used to assess cytotoxicity. MG132 proteasomal inhibitor and sodium arsenite (NaArs) were used to investigate oxidative stress, and 50 µM of metformin was tested for its protective effects against oxidative stress in hiPSC-derived neurons. Metformin treatment did not affect cell viability, neuronal differentiation, or trigger reactive oxygen species (ROS) generation in healthy hiPSC-derived motor neurons. Additionally, mitochondrial membrane potential (MMP) loss was not observed at 50 µM metformin. Metformin effectively protected neurons from stress agents and elevated the expression of antioxidant genes when treated with MG132. However, an interplay between MG132 and metformin resulted in lower expression of Nrf2 and NQO1 compared to the MG132 group alone, indicating reduced JC-1 aggregate levels due to MG132 proteasomal inhibition. Metformin upregulated antioxidant genes in hiPSC-derived neurons under stress conditions and protected the cells from oxidative damage.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"15"},"PeriodicalIF":2.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Omics Analysis of Hippocampus in Rats Administered Trimethyltin Chloride.","authors":"Douaa Zakaria, Tomoki Yamashita, Yohei Kosugi","doi":"10.1007/s12640-025-00737-3","DOIUrl":"10.1007/s12640-025-00737-3","url":null,"abstract":"<p><p>Trimethyltin chloride (TMT) is a neurotoxicant that damages the central nervous system (CNS) and triggers neurodegeneration. This study used multi-omic data, including transcriptomics and proteomics of the rat hippocampus, to identify differentially expressed genes and proteins in TMT-induced neurotoxicity over time, related to neuro-axonal damage marked by plasma Neurofilament Light (NfL) levels. Data were collected at 12, 24, 48, 72, and 168 h post-TMT administration. NfL levels surged at 72 and 168 h, confirming neuro-axonal damage. Transcripts of genes in the chemokine signaling pathway (Cxcl10, Cxcl12, Cxcl14, Cxcl16), apoptosis pathway (Caspase-3, PARP1, CTSD), and TNF signaling pathway (TNFR1, MMP9, ICAM-1, TRAF3) showed significant differential expression starting from 48 h, preceding the NfL increase, suggesting their roles in neuro-axonal damage. Additionally, 11 Alzheimer's disease-related proteins, with significant changes from 72 to 168 h, were detected only in the proteomic dataset, indicating post-translational modifications might be crucial in neurotoxicity. Pathway analysis revealed that neurodegeneration and Alzheimer's disease pathways were among the top 15 affected by TMT-induced gene regulation, aligning with the involvement of TNF signaling, apoptosis, and chemokine signaling in neurodegeneration. This research highlighted the value of longitudinal omics studies, combined with pathway enrichment, gene-disease association, and neuro-axonal damage biomarker analyses, to elucidate neurotoxicant-induced neurodegeneration. Findings from this study could enhance the understanding of TMT-induced neurotoxicity, potentially informing future therapeutic strategies and preventive measures.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"13"},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Memory Enhancement Effects of Aminopyrimidine Derivatives Using the Scopolamine Model of Dementia in Mice.","authors":"Behnaz Landi, Mona Khoramjouy, Alireza Ghavami Lahij, Sajjad Fazelkia, Salimeh Amidi, Farzad Kobarfard, Mehrdad Faizi","doi":"10.1007/s12640-025-00736-4","DOIUrl":"10.1007/s12640-025-00736-4","url":null,"abstract":"<p><p>Aminopyrimidine compounds have been gaining traction in the field of drug discovery in recent years due to their emergence as multi-targeted molecules. This makes them perfect candidates as agents for cognitive improvement, as cognitive decline is a multifaceted condition. We aim to evaluate their potential for memory enhancement, specifically through their cholinergic properties. This work examines the properties of seven aminopyrimidine derivatives and their effects on memory acquisition and retention. These compounds were administered to NMRI mice after the induction of amnesia by scopolamine, and memory impairment and improvement were assessed using passive avoidance and spontaneous alternation tests with the drug donepezil as the positive control group. These compounds were also analyzed using docking and ADME prediction studies to determine potential affinity to the acetylcholinesterase enzyme, and characterize pharmacokinetic properties, respectively. Additionally, in vitro inhibition of cholinesterase was evaluated. Results showed that three of the seven compounds significantly increased cognition in both behavioral tests. Software analysis suggested allosteric inhibition or modulation of acetylcholinesterase, signifying the potential of these compounds for further optimization and eventual utilization for treatment of cognitive impairment cases.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"12"},"PeriodicalIF":2.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Naringin on Cognitive-Behavioral Functions, CREB/BDNF Signaling, Cholinergic Activity, and Neuronal Density in the Hippocampus of an MSG-Induced Obesity Rat Model.","authors":"Bahareh Alijani, Mohammad Amin Edalatmanesh, Heydar Aghababa","doi":"10.1007/s12640-025-00733-7","DOIUrl":"10.1007/s12640-025-00733-7","url":null,"abstract":"<p><p>The global rise in obesity and overweight over the past few decades has led to numerous associated disorders, including cognitive deficits. This study evaluate investigates the effects of Naringin (Nar) on memory and learning, anxiety-like behaviors, brain-derived neurotrophic factor (BDNF), cAMP responsive element binding protein (CREB), acetylcholinesterase (AChE) activity, and neuronal density in the CA₁/CA₃ subfields of the hippocampus in an MSG-induced obese obesity rat model. Forty-eight male Wistar rat pups were randomly divided into four groups: Control, MSG, MSG + Nar50, and MSG + Nar100. MSG (4 g/kg BW) was administered subcutaneously in the cervical region from PND 2 to PND10, while Nar (50 mg/kg BW and 100 mg/kg BW) was administered orally from PND30 to PND42. After the treatment period, cognitive (working memory and passive avoidance) and anxiety-related tests (elevated plus maze and novelty-suppressed feeding test) were performed. Subsequently, hippocampal protein level of BDNF and CREB/BDNF gene expression, AChE activity and neuronal density in the CA₁ and CA₃ regions of the hippocampus were measured. Relative to the MSG group, the Nar-treated rats demonstrated improvements in spatial working memory, reduced anxiety-related behaviors, elevated hippocampal CREB and BDNF genes and BDNF protein levels, and reduced AChE activity. Additionally, Nar treatment increased neuronal density in the CA₁/CA₃ subfields of the hippocampus. These findings suggest that Nar enhances cognitive function and mitigates anxiety in MSG-induced obese rats by modulating CREB/BDNF signaling pathway, inhibiting AChE, and exerting neuroprotective effects in the hippocampus.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"11"},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Specific Outcomes in a Rat Model of Early-Life Stress Due to Adverse Caregiving.","authors":"Jazmín Grillo Balboa, Ailén A Colapietro, Verónica I Cantarelli, Marina F Ponzio, Marianela N Ceol Retamal, María E Pallarés, Marta C Antonelli, Mariela Chertoff","doi":"10.1007/s12640-025-00731-9","DOIUrl":"10.1007/s12640-025-00731-9","url":null,"abstract":"<p><p>Early parental care is critical for the development of cortico-limbic circuits regulating stress responses and emotional well-being. Conversely, infant maltreatment can increase susceptibility to mood disorders-such as anxiety and depression-and impair stress-coping abilities. Here, we employed the Scarcity-Adversity Model (SAM) in rats, limiting nesting resources from postnatal days 8-12, to examine its effects on maternal and adult offspring behavior. SAM-exposed mothers exhibited fragmented care and increased violence towards pups. By postpartum day (PPD) 13, maternal fecal corticosterone metabolites (FCM) were elevated, indicating heightened stress. At weaning, SAM dams also showed increased anxiety-like behavior in the Elevated Plus Maze (EPM), suggesting significant emotional alterations. In adulthood, SAM-exposed offspring underwent anxiogenic tests. Both male and female SAM offspring showed increased latency to enter open arms and reduced risk-assessment in the EPM, though females displayed anxiolytic-like behavior in the Light-Dark Box. Male SAM rats had reduced locomotion in the Open Field, earlier onset and increased immobility in the Forced Swim, and increased latency to groom in the Sucrose Splash. When exposed to acute stress, male SAM rats had lower FCM levels, consistent with their passive stress reactivity. These findings confirm SAM induces long-lasting, sex-specific changes in risk-taking, novelty responsiveness, and stress reactions, underscoring the importance of early nurturing in promoting well-being and reducing psychopathological risk.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 2","pages":"10"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}