BMC Neuroscience最新文献

{"title":"Cognitive speed-accuracy dissociation in multiple myeloma: a cross‑sectional study.","authors":"Sumayyah Patel, Christopher Parrish, Frances Seymour, Melanie Burke","doi":"10.1186/s12868-026-01024-3","DOIUrl":"10.1186/s12868-026-01024-3","url":null,"abstract":"<p><strong>Purpose: </strong>This study examined whether adults with Multiple Myeloma (MM) show measurable cognitive differences compared with neurologically healthy controls. The primary research question focused on identifying domain-specific cognitive deficits and determining whether standard screening tools adequately capture cognitive abilities.</p><p><strong>Methods: </strong>A cross-sectional design compared 45 adults with MM to 40 controls. Participants completed 40-50 min of cognitive and psychological assessments, including the Montreal Cognitive Assessment (MoCA), validated measures of mood and daily functioning, and a digitised cognitive battery assessing key cognitive domains. Group differences in reaction time (RTs) and accuracy were analysed using ANCOVAs adjusting for age and education. Bayesian analyses and EZ drift diffusion modelling (EZ-DDM) were used to characterise evidence strength, prevalence of domain-level inefficiencies, and latent decision-making processes.</p><p><strong>Results: </strong>MoCA scores were lower in the MM group, although the group difference did not reach statistical significance. However, a higher proportion of MM participants met the criteria for possible cognitive impairment compared with controls. At the computerised task level, no significant group differences were observed in accuracy or mean RT. RT analyses showed significant effects of cognitive domain, age, and education, but no overall group effect or interaction. Despite this, threshold-based Bayesian analyses indicated that approximately 22% of MM participants exhibited multi-domain RT inefficiencies, with variability most evident in cognitive flexibility and semantic processing. Accuracy-based performance was largely preserved across both groups, with no participants exceeding impairment thresholds. EZ-DDM indicated that group differences were driven by reduced drift rates and prolonged non-decision times in MM, suggesting slower evidence accumulation with slower sensory encoding and/or motor execution.</p><p><strong>Conclusion: </strong>Cognitive differences in MM appear subtle and primarily expressed in processing efficiency rather than accuracy. Conventional screening measures and standard group comparisons may not fully capture this variability, particularly at the individual level. These findings support the use of more sensitive analytic approaches to characterise heterogeneous cognitive profiles in MM. Longitudinal and neuroimaging studies may help clarify whether observed inefficiencies reflect underlying neural changes associated with disease and treatment, and how these relate to functional outcomes.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418491","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}

{"title":"Iron overload induces ROS-mediated neural stem/progenitor cells apoptosis via mTOR pathway.","authors":"Fengchun Zhao, Wei Quan, Qian Zhang, Yi Yin, Yibin Jiang, Xuyang Zhang, Huanhuan Li, Chao Zhang, Lan Li, Shengli Hu, Fei Li, Rong Hu","doi":"10.1186/s12868-026-01021-6","DOIUrl":"10.1186/s12868-026-01021-6","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a health challenge resulting in death or disability. Iron overload has been identified as one of post-ICH damaging factors. However, the impact of iron overload, as well as the underlying mechanisms, on neural stem/progenitor cells (NSPCs) remains unknown. In this study, we found that iron overload induced significant NSPC death in a dose-dependent manner. Interestingly, iron overload increased the number of early and late apoptotic cells and the expression of caspase-3 in NSPCs. Moreover, iron overload was highly correlated with enhanced intracellular reactive oxygen species (ROS) generation and loss of mitochondrial integrity. Further, iron overload activated mTOR signaling and downregulated AMP-activated protein kinase (AMPK) phosphorylation. Importantly, drugs that eliminate ROS or activate AMPK prevented this event, as well as apoptosis of NSPCs. These results indicate that post-ICH iron overload in the brain induces excessive ROS generation and leads to NSPC death by regulating mTOR and AMPK signaling.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374408","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}

{"title":"Combined maternal separation and limited bedding-nesting increase goal tracking, delay discounting, and impulsive action, and moderate sign-tracking-perseverance associations in male rats.","authors":"Julian Cifuentes, Mónica Arias-Higuera, Cesar Acevedo-Triana, Michael J Hylin, Lucas Pozzo-Miller, Camilo Hurtado-Parrado","doi":"10.1186/s12868-026-01018-1","DOIUrl":"10.1186/s12868-026-01018-1","url":null,"abstract":"<p><strong>Background: </strong>Extensive research with rodent models has shown detrimental effects of early-life adversity (ELA) on behavioral (e.g., impulsive behavior, anxiety, and depression) and neurobiological processes (e.g., alterations of neuroendocrine processes and maturation of brain areas). However, heterogeneous methodologies, including types and variations of ELA manipulations could have contributed to inconsistent findings across studies. Recent research indicates that the combination of the two most widely implemented rodent ELA protocols, Maternal Separation (MS) and Limited Bedding/Nesting (LBN), produces consistent and robust behavioral effects. We assessed the effects of combined MS-LBN on four processes linked to both ELA and behavioral disorders in later stages of life: incentive salience of reward cues, and impulsive choice, action, and persistence/perseverance.</p><p><strong>Methods: </strong>Sixteen male Sprague Dawley rats were divided in groups of combined MS-LBN during postnatal days 2-21 and without ELA. They were exposed to an Autoshaping Pavlovian conditioning task (AUT), a delay-discounting task (DDT), and acquisition and extinction of a multiple schedule of reinforcement with long and short Variable Intervals (VI) across a span of 18 weeks.</p><p><strong>Results: </strong>Compared to the No-ELA group, ELA rats displayed higher goal-tracking during the AUT (higher nose-poking in the food-delivery location), higher impulsive choice during test and 7-week re-test of the DDT (preference for the smaller-sooner reinforcer over the larger-later), and less efficient responding during the long-interval schedule of reinforcement (more unnecessary responses per pellet). Associations between autoshaping and reinforcement-schedule performance were identified, with ELA moderating the relationship between sign tracking and efficiency during training and persistence/perseverance during extinction.</p><p><strong>Conclusions: </strong>Combined MS-LBN was associated with task-specific changes in reward-related and impulsive behavior in male rats. These complex patterns of disruptions across behavioral processes adds further support to the notion that combined ELA protocols are promising robust models of adverse rearing in humans, which often entails multiple stressors.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350633","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}

{"title":"Glycine as a potential neuroprotective adjuvant to reduce cisplatin-induced brain inflammation in mice.","authors":"Hafiz Muhammad Obaid Kazmi, Muhammad Umer Suleman, Syeda Iqra Maqsood, Shahbaz Azam Khan, Iqra Khadam, Saima Mumtaz Khattak, Umer Khalil, Muhammad Mursaleen, Muhammad Mustafeez Waheed Jami, Sumaira Javed, Najeeb Ullah, Muhammad Ikram, Marwan Alqumbaey","doi":"10.1186/s12868-026-01023-4","DOIUrl":"10.1186/s12868-026-01023-4","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin-induced neurotoxicity is driven in part by neuroinflammation and oxidative injury in vulnerable brain regions. Glycine has anti-inflammatory and antioxidant properties that may offer neuroprotection against chemotherapy-related brain damage.</p><p><strong>Methods: </strong>Twenty-five adult male BALB/c mice were randomized into five groups (n = 5/group) Group 1 received cisplatin for 14 days; Group 2 received cisplatin plus glycine for 14 days; Group 3 received cisplatin for 28 days; Group 4 received cisplatin for 14 days followed by glycine for 14 days; and Group 5 received cisplatin for 28 days with glycine introduced from day 14 to day 28. Cisplatin was administered intraperitoneally at 3 mg/kg every fourth day, and glycine was given subcutaneously at 1 g/kg daily. The primary outcome was serum TNF-α measured by ELISA. Secondary outcomes were neuronal integrity and optical density in the hippocampus and frontal cortex assessed by Nissl staining. Data were analyzed using one-way ANOVA with Tukey post-hoc testing.</p><p><strong>Results: </strong>Serum TNF-α levels differed significantly among groups (F = 230.422, p < 0.001). Mean TNF-α concentrations were 150.0 pg/mL in Group 1, 130.2 pg/mL in Group 2, 201.4 pg/mL in Group 3, 159.4 pg/mL in Group 4, and 171.0 pg/mL in Group 5. Prolonged cisplatin exposure (Group 3) produced the highest TNF-α levels, whereas concurrent glycine administration during the 14-day regimen (Group 2) resulted in the lowest levels. Compared with the 28-day cisplatin group, both delayed glycine treatment (Group 4) and glycine introduced during the second half of cisplatin exposure (Group 5) were associated with lower TNF-α concentrations. Histological analysis demonstrated reduced Nissl staining intensity and neuronal preservation in cisplatin-only groups, particularly Group 3, whereas glycine-treated groups showed better preservation of neuronal architecture and optical density in the hippocampus and frontal cortex.</p><p><strong>Conclusion: </strong>Glycine attenuated cisplatin-induced neuroinflammation and preserved neuronal integrity in the hippocampus and frontal cortex of mice. These findings support further preclinical evaluation of glycine as a low-cost adjuvant strategy to reduce chemotherapy-associated neurotoxicity.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343851","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}

{"title":"Using combined ROC curves to improve the diagnostic usefulness of glutaminase, prostaglandins, and 8-isoprostane as biomarkers of autism spectrum disorders;Role in the Glu-GABA-Gln cycle.","authors":"Afaf El-Ansary, Hanan A Alfawaz, Manan Alhakbany, Ramesa Shafi Bhat, Geir Bjørklund, Laila Y Al-Ayadhi","doi":"10.1186/s12868-026-01020-7","DOIUrl":"10.1186/s12868-026-01020-7","url":null,"abstract":"<p><p>Due to delayed symptoms and dependence of behavioral assessment, early diagnosis of autism spectrum disorder remains challenging. Identification of multivariate biomarker for the etiological mechanisms of ASD may enhance diagnostic accuracy. Multivariable logistic regression combines many predictors into a single risk score (linear predictor), resulting in an optimised ROC curve that enhances diagnostic accuracy over individual markers. The method comprises modelling a binary result, determining the likelihood, and visualising ROC based on the projected probabilities, which often improves individual marker AUCs. In the present study a diagnostic performance for a biomarker panel reflecting glutamatergic dysfunction, oxidative stress, and neuroinflammation was evaluated. Plasma levels of glutaminase, 8-isoprostane, and prostaglandin E₂ (PGE₂) obtained from 44 children with ASD and 40 age-matched controls were evaluated using receiver operating characteristic (ROC) analysis, both individually and in combined ROC models. Glutaminase showed significant negative correlations with both 8-isoprostane and PGE₂, whereas a positive correlation was observed between 8-isoprostane and PGE₂. All the three-biomarker showed good diagnostic performance for ASD on its own with statistically significant (p = 0.001) values of AUC of 0.830 for glutaminase, AUC of 0.815 for 8-Isoprostane and AUC of 0.818 for PGE₂. However combined ROC modeling substantially improved diagnostic accuracy by achieving high apparent discriminative performance with AUC value of 0.977 with 92.3% sensitivity and 100.0% specificity. In conclusion, the diagnostic usefulness of independent glutaminase, 8-isoprostane, and prostaglandin E₂ (PGE₂) biomarkers may be enhanced by combining ROC. Combined markers show strong apparent discriminating power in a case-control method, but estimates are biassed towards optimism and are not diagnostic. Comprehensive assay validation, calibration, and clinically representative cohorts (including females and relevant differentials) are required for replication.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"27 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315414","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}

{"title":"Age-related susceptibility to paraquat-induced neurotoxicity in male wistar rats: effects on neurobehaviour, substantia nigra cytoarchitecture, and alpha-synuclein levels.","authors":"Kelechi Ichie, Azuoma Asomugha, Izuchukwu Okafor","doi":"10.1186/s12868-026-01019-0","DOIUrl":"10.1186/s12868-026-01019-0","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder strongly associated with dopaminergic neuronal degeneration and alpha-synuclein pathology. Paraquat (PQ) has been implicated in Parkinsonian neurodegeneration; however, the influence of age on susceptibility to PQ-induced neuropathology remains insufficiently characterized.</p><p><strong>Aim: </strong>This study investigated age-dependent effects of paraquat exposure on neurobehaviour, substantia nigra histomorphology, and serum alpha-synuclein levels in male Wistar rats.</p><p><strong>Methods: </strong>Sixty-three male Wistar rats were assigned into juvenile, young adult, and adult age categories, each further subdivided into control, PQ-treated, and PQ+recovery groups. Paraquat (10 mg/kg, intraperitoneally) was administered twice weekly for three weeks. Recovery groups were maintained for a two-month post-exposure period. Neurobehavioral assessments were conducted to evaluate locomotor and anxiety-related functions. Serum and nigral alpha-synuclein concentrations were quantified using enzyme-linked immunosorbent assay (ELISA), while histological examination of the substantia nigra was performed to assess neuronal integrity.</p><p><strong>Results: </strong>Adult rats exhibited a significant reduction in locomotor activity following PQ exposure (p = 0.020) and showed more prominent histopathological alterations within the substantia nigra compared with juvenile and young-adult animals. Although improvement in tissue architecture was observed following paraquat withdrawal, residual alterations persisted, particularly in adults. Nigral alpha-synuclein concentrations did not differ significantly among treatment groups in any age cohort. Serum alpha-synuclein levels were similarly unchanged in most groups, except for a reduction observed in recovering young-adult animals (p = 0.039).</p><p><strong>Conclusion: </strong>Age influences vulnerability to PQ-induced neurotoxicity, with adult animals showing greater susceptibility to behavioral and histological damage. However, serum total alpha-synuclein levels did not consistently parallel central neuropathology, suggesting limited reliability as a standalone peripheral biomarker of PQ-induced Parkinsonism.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275852","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}

{"title":"Proteomic profiling reveals structural and adhesion pathways regulated by the inverted CHRFAM7AΔ2bp variant in human neural progenitor cells.","authors":"Natalie Erickson, Ivanna Ihnatovych, Andras Szabados, Kinga Szigeti, Nadine Kabbani","doi":"10.1186/s12868-026-01016-3","DOIUrl":"10.1186/s12868-026-01016-3","url":null,"abstract":"<p><p>The CHRNA7 gene, located on chromosome 15q13.3, encodes the α7 nicotinic acetylcholine receptor (α7 nAChR) subunit and lies within a genomic region characterized by high recombination rates and associations with multiple neuropsychiatric disorders. Within this region, the human specific gene CHRFAM7A arose through partial duplication, rearrangement, and fusion between CHRNA7 and FAM7A. The direct CHRFAM7A allele has been shown to negatively regulate α7 nAChR function. The inverted allele (CHRFAM7AΔ2bp), harboring a two-base pair deletion in exon 6, is linked to schizophrenia, bipolar disorder, and other psychiatric conditions. In this study, we investigated how the presence of the CHRFAM7AΔ2bp allele alters the cellular proteome. Using high-throughput proteomic analysis by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), we characterized protein expression in neuronal progenitors differentiated from isogenic human induced pluripotent stem cell (iPSC) lines representing CHRFAM7AΔ2bp and CHRFAM7A-null genotypes. Comparative analysis identified 129 differentially expressed proteins enriched in pathways related to extracellular matrix organization, collagen biosynthesis, and cell adhesion. Functional assays further demonstrated differences in matrix adhesion between CHRFAM7A-null and CHRFAM7AΔ2bp-derived progenitors. These results suggest that the CHRFAM7AΔ2bp variant influences cellular structure through modulation of adhesion matrix-interaction proteins. This work provides insight into molecular mechanisms that may underlie increased neurodisease vulnerability associated with this genotype.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249205","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}

{"title":"Taurine reverses long-term memory deficits caused by LPS induced neuroinflammation.","authors":"Maria Vaitsa Loch Haskel, Letícia Stresser da Silva Vequi, Marianna Wirthmann Pompeo Flauzino, Vinicius da Silva Correa, Cláudia Sirlene Oliveira, Meire Ellen Pereira, Elizama de Gregório, Juliana Sartori Bonini, Weber Claudio da Silva","doi":"10.1186/s12868-026-01017-2","DOIUrl":"10.1186/s12868-026-01017-2","url":null,"abstract":"<p><strong>Background: </strong>Despite neuroinflammation being an initially protective response made by the central nervous system (CNS), as it becomes chronic, it can lead to neuronal damage since the cytokines which are released by microglia potentialize cellular death due to excitotoxicity, and this, in turn, promotes the release of pro-inflammatory mediators, feeding this way a self-sustaining cycle of neuroinflammatory response, which favor subsequent neurodegeneration. Given the fact that until this moment, there are not any therapeutic alternatives able to stop the neurodegeneration, the objective of the present work was to evaluate the putative neuroprotector effect of taurine, a partial glycinergic ionotropic receptor agonist, and also a GABA_A receptor agonist, in a neuroinflammation animal model.</p><p><strong>Method: </strong>For this intent, the oral taurine administration was evaluated on mnemonic impairing caused by LPS induced neuroinflammation in male Wistar rats. Such effects were investigated on recent and late spatial long-term memory and aversive memory in the behavioural tasks Morris water maze (MWM) and context fear conditioning (CFC), respectively. In addition, we investigated the effect of orally administered taurine on hippocampal neuronal density and on hippocampal levels of TNF-α and IL-4.</p><p><strong>Results: </strong>Taurine, when orally administered for 30 days, in the doses of 20 and 200 mg/kg, was able to reverse the mnemonic impairment caused by neuroinflammation on recent and remote spatial long-term memory, and in the dose of 200 mg/kg, it also was able to do the same on aversive long-term memory. In the doses of 20 and 200 mg/kg, taurine was also able to reverse the LPS-induced increase in hippocampal TNF-α levels.</p><p><strong>Conclusion: </strong>Taurine, when orally administered in a pathological context characterized by neuroinflammatory background, as it was induced in this work, can perform a dose-dependent neuroprotective effect, probably by acting in an excitotoxic scenario in which the activation of hyperpolarizing receptors can be welcomed.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222963","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}

{"title":"Clofazimine against cerebral toxoplasmosis in diabetic and dexamethasone-immunosuppressed mice: ultrastructural and semiquantitative transmission electron microscopic study.","authors":"Mennat-Elrahman A Fahmy, Amany A Abdel-Aal, Soad I Hassan, Maisa A Shalaby, Marwa Esmat","doi":"10.1186/s12868-026-01008-3","DOIUrl":"10.1186/s12868-026-01008-3","url":null,"abstract":"<p><p>Cerebral toxoplasmosis is a common opportunistic parasitic infection of the CNS caused by the Toxoplasma gondii parasite. Host immunosuppression can affect disease outcomes. To explore the changes in the cerebral cortical ultrastructure accompanying the infection in different immune-altered models and to find an effective treatment against the infection, we tested the possible therapeutic effect of clofazimine (CFZ) (the FDA-approved antimycobacterial drug) against the infection using 60 male CD1 Swiss Albino mice divided into 6 groups: 3 dexamethasone (DEX)- treated groups (DEX-only, DEX-infected, and DEX-infected-treated), and 3 streptozotocin (STZ)-induced type 1 diabetic groups (STZ-only, STZ-infected, STZ-infected-treated). The worst ultrastructural changes were observed in the diabetic and diabetic-infected groups, characterized by a significant increase in neuronal apoptotic and necrotic nuclei (P < 0.05) and changes in the numbers and structure of glial cells compared to the DEX and DEX-infected groups. CFZ (at a dose of 10 mg/kg/day for 3 days starting on 45th day post infection) significantly improved cortical neuronal ultrastructural changes in both models (P < 0.05), reduced microglial numbers, increased astrocyte numbers, and restored brain capillary integrity and axonal growth, in addition to significantly reducing mature cyst numbers in both models (P < 0.05). However, the drug didn't reduce the number of atrophic and necrotic cysts in the infected-treated groups. So, in our study, CFZ showed preclinical promise in treating experimental cerebral toxoplasmosis and reducing the parasitic cyst burden, highlighting the adverse impact of the host's altered immune status on brain tissue and the course of the infection, especially in diabetes.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155228","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}

{"title":"Molecular marker of memory formation reveals complex mechanisms of developmental learning.","authors":"Rebecca M Butler, Konstance D Delis, Kruthika V Maheshwar, Karelys D Montañez, Selin Yalcindag, Sarah E London","doi":"10.1186/s12868-026-01013-6","DOIUrl":"10.1186/s12868-026-01013-6","url":null,"abstract":"<p><p>The intersection of age- and experience-dependent processes influence learning throughout development, and developmental learning can have long-term effects on behavior. Phosphorylation of ribosomal protein S6 phosphorylation (pS6) is required in active ribosomes, and new protein synthesis is a conserved mechanism that supports long term memory formation. As such, pS6 fluctuations in brain regions processing experience can provide insight into shifts in the ability for learning and memory. Juvenile male and female zebra finch songbirds (Taeniopygia guttata) perform sensory song learning in ways that affect their adult behaviors. As adults, both sexes perform song recognition learning. Both juvenile and adult types of sensory learning invoke the auditory forebrain. Prior reports established a pS6 song response in the auditory forebrain in Posthatch day 30 juvenile males but not females, and not in younger birds. This was intriguing because the experience-dependent pS6 increase tracked with the onset of the critical period for juvenile sensory song learning in males, and behavioral data indicated that females also effectively learn at P30, though they may not have a critical period. Further, by adulthood (> Posthatch day 90), both male and female auditory forebrains showed an equivalent increase in pS6 after hearing song in patterns consistent with effective recognition learning. Here, to further test the relationships between a crucial molecular marker of active learning processes and the developmental trajectory of juvenile sensory song learning and the emergence of adult-like song recognition learning, we assessed the effect of age and sex, as well as the absence of tutor experience, a manipulation that extends the critical period for developmental learning in males, on the phosphorylation of S6 within the auditory forebrain. Outcomes highlight the complexity of molecular mechanisms across developmental learning and reveal questions to be addressed by further inquiry.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052360","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}