BMC Neuroscience[JOURNAL]
Sun
200 papers
Involvement of CB1 cannabinoid receptors in methamphetamine-related decision-making and social behavior deficits.
Mousavi T, Hatami N, Niknamfar S … +5 more , Naseri M, Rafaiee R, Tamijani SMS, Ranaiy MS, Ghazvini H
BMC Neurosci · 2026 Feb · PMID 41731375 · Full text
BACKGROUND: Methamphetamine (METH) abuse is associated with profound cognitive and behavioral impairments, notably in decision-making and social interaction. Emerging evidence suggests the endocannabinoid system, particu...
BACKGROUND: Methamphetamine (METH) abuse is associated with profound cognitive and behavioral impairments, notably in decision-making and social interaction. Emerging evidence suggests the endocannabinoid system, particularly CB1 receptors (CB1Rs), plays a modulatory role in these processes. This study investigated whether pharmacological modulation of CB1Rs can alter METH-induced deficits in decision-making, social behavior, and anxiety in a rodent model. METHODS: Adult male Wistar rats were administered METH and treated with either a CB1R agonist WIN55,212-2 (WIN; 3 mg/kg; i.p) or antagonist (Rimonabant;1 mg/kg; i.p.). Behavioral assessments included effort-based decision-making via the Y-maze barrier task, social behavior tests, and anxiety evaluation using the elevated plus maze. RESULTS: METH exposure significantly reduced high-reward choices in effort-based tasks and impaired multiple domains of social behavior. It also induced anxiety-like behaviors. Rimonabant treatment partially reversed these effects, improving decision-making performance, enhancing social interactions, and reducing anxiety-related responses. In contrast, WIN did not significantly alleviate METH-induced behavioral impairments. CONCLUSION: CB1R antagonism via Rimonabant may mitigate METH-induced cognitive and social deficits, underscoring the therapeutic potential of targeting the endocannabinoid system in stimulant-related neuropsychiatric disorders. These findings highlight CB1R antagonists as promising agents for future interventions in METH addiction and its associated behavioral disruptions. CLINICAL TRIAL NUMBER: Not applicable.
Slc6a9 is distributed in glial cells and neurons across several nervous system regions, whereas Slc6a5 is more restricted to neurons in the caudal brain.
Ceder MM, Lagerström MC
BMC Neurosci · 2026 Feb · PMID 41703440 · Full text
BACKGROUND: The glycinergic system constitutes a main source of inhibitory regulation in the central nervous system. Glycine transporters (GLYT1 and GLYT2), encoded by Slc6a9 and Slc6a5, respectively, are responsible for...
BACKGROUND: The glycinergic system constitutes a main source of inhibitory regulation in the central nervous system. Glycine transporters (GLYT1 and GLYT2), encoded by Slc6a9 and Slc6a5, respectively, are responsible for glycine reuptake and clearance from the synaptic cleft, thereby maintaining neurotransmitter homeostasis. Emerging evidence from pharmacological and mechanistic studies has highlighted GLYTs as promising therapeutic targets for psychiatric disorders and persistent pain. Nevertheless, data on anatomical and cellular distribution of GLYTs and sex-dependent differences in GLYT expression remain limited. METHODS: To address this gap, the aim of this study was to examine the Slc6a9 and Slc6a5 mRNA expression across mouse brain regions and peripheral organs using three complementary approaches focusing on mRNA expression: re-analysis of single-cell RNA sequencing data, quantitative RT-PCR, and RNAscope. RESULTS: Both genes were detected in multiple brain regions, with Slc6a9 exhibiting a broader distribution in both glial cells and neurons, while Slc6a5 was more restricted to neurons. Sex-dependent differences were detected for Slc6a9 in the amygdala and thalamus, liver, intestine, spleen, kidney and genitalia using quantitative RT-PCR, and for Slc6a5 in the cortex, striatum, hippocampus, and spinal cord using quantitative RT-PCR. Spatial analysis of the glycine transporters showed that Slc6a9 can be found in several brain regions spanning the rostral to the caudal axis, in both glial cells and neurons, while Slc6a5 was more restricted to the caudal brain regions. CONCLUSIONS: In general, in regions where differences were detected using quantitative RT-PCR, higher expression levels were observed in male mice. Moreover, Slc6a9 expression was found to occur in both glial cells, such as astrocytes, oligodendrocytes and ependymal cells, as well as both excitatory and inhibitory neurons, while Slc6a5 mainly occurred in inhibitory neurons. These findings provide novel insights into the spatial and sex-dependent expression of glycine transporters.
Acetyl-11-keto-β-boswellic acid attenuates tau oligomer-induced neurotoxicity in neuroblastoma cell model.
Pourhossein S, Mianrood IB, Khatami SH … +8 more , Ehtiati S, Ghasemian M, Mokhtari F, Ahmadzade R, Goudarzi M, Hamed N, Namvarjah F, Karima S
BMC Neurosci · 2026 Feb · PMID 41680609 · Full text
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by microtubule destabilization, neuroinflammation, and tau pathology. Among the proposed therapeutic approaches, acetyl-11-ke...
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by microtubule destabilization, neuroinflammation, and tau pathology. Among the proposed therapeutic approaches, acetyl-11-keto-β-boswellic acid (AKBA), a bioactive triterpene from Boswellia serrata, has gained attention due to its multiple neuroprotective mechanisms, including microtubule stabilization, anti-inflammatory activity, antioxidant effects, and promotion of neurogenesis. In this study, we aimed to investigate the neuroprotective effect of AKBA against tau oligomer-induced cytotoxicity in SH-SY5Y neuroblastoma cells. RESULTS: Recombinant human tau protein was expressed, purified, and oligomerized, and the formation of oligomers was confirmed by thioflavin T fluorescence and dynamic light scattering (DLS). SH-SY5Y cells were then treated with AKBA and exposed to tau oligomers. Cell viability was assessed via MTT assay, and apoptosis was evaluated by flow cytometry. The morphology of tau aggregates was visualized using transmission electron microscopy. CONCLUSIONS: Our findings demonstrated that AKBA significantly reduced tau oligomer-induced cytotoxicity and enhanced cell viability. These results suggest that AKBA, through its multifaceted protective mechanisms, holds promise as a potential therapeutic agent for the treatment of tauopathies such as Alzheimer's disease. CLINICAL TRIAL NUMBER: Not applicable.
MEF2A-mediated inhibition of ischemic stroke injury via the PI3K/AKT pathway: a comprehensive bioinformatics and in vitro study.
Zhang T, Cheng J, Tian Y … +1 more , Hai Y
BMC Neurosci · 2026 Feb · PMID 41622144 · Full text
BACKGROUND: Thrombosis or embolism causes blood flow stoppage, resulting in ischemic stroke (IS), the most frequent clinical cerebrovascular disorder. It accounts for more than 80% of all strokes and has a significant di...
BACKGROUND: Thrombosis or embolism causes blood flow stoppage, resulting in ischemic stroke (IS), the most frequent clinical cerebrovascular disorder. It accounts for more than 80% of all strokes and has a significant disability and mortality rate. Regulating critical targets to stop the ischemia pathophysiological cascade and preserve brain cells is essential for treating IS. METHODS: We included a deCODE analysis encompassing data on cis-acting variations for 4719 blood proteins. The IS summary statistics consist of 11,929 cases and 472,192 controls. We identified blood proteins associated with IS susceptibility using the Mendelian randomization (MR) method. We comprehensively analyzed the GSE58294 dataset, including differential expression gene identification, functional enrichment analysis, weighted gene co-expression network analysis, least absolute shrinkage and selection operator analysis, and transcription factor identification. The expression patterns of key genes were identified using single-cell sequencing data. The oxygen-glucose deprivation/reperfusion (OGD/R) model was established, and myocyte enhancer factor 2 A (MEF2A) was overexpressed in Neuro-2a/PC12 cells using an overexpression vector. We used CCK-8 and western blotting to observe the cell viability, oxidative stress level, and p-PI3K and p-Akt protein expression. RESULTS: We discovered 73 blood proteins related to IS, and the sensitivity analysis findings supported the causal associations. The MR results and bioinformatics underwent a thorough examination, revealing MEF2A as a transcription factor involved in the development of IS. Single-cell sequencing results revealed that MEF2A was mostly expressed in microglia and endothelial cells. Additional in vitro experiments showed that overexpression of MEF2A could significantly mitigate OGD/R-induced Neuro-2a/PC12 cell injury and oxidative stress, potentially associated with increased PI3K/Akt protein production. CONCLUSION: This study, using MR analysis, transcriptomics, and in vitro experiments, identified the transcription factor MEF2A as a potential target for treatment. This gives preclinical evidence for drug development. CLINICAL TRIAL NUMBER: Not applicable.
Modulation of stress and neuroplasticity biomarkers via rhythmic vocalization: a controlled study on NDNF, cortisol, and monoamines.
Okur S, Bayraktar B
BMC Neurosci · 2026 Jan · PMID 41612199 · Full text
BACKGROUND: The aim of this study is to investigate the effect of reciting the Quran (from Mushaf) on serotonin, dopamine, NDNF, and cortisol levels in relation to mental well-being. METHODS: This study was conducted on...
BACKGROUND: The aim of this study is to investigate the effect of reciting the Quran (from Mushaf) on serotonin, dopamine, NDNF, and cortisol levels in relation to mental well-being. METHODS: This study was conducted on a sample of university students who know how to read the Quran in Türkiye, selected by a non-probability method, with a pre-test-post-test control group and a longitudinal design; the assignment to the groups was also done randomly. The research was carried out with 72 university students (36 female, 36 male), aged 19–30, who know how to read the Quran and do not have any health problems. Two groups were formed: a 36-person experimental group and a 36-person passive resting control group. The Mental Well-Being Scale and a personal information form were used to evaluate the participants’ well-being status. Salivary serotonin, dopamine, NDNF, and cortisol levels were examined using the ELISA technique in samples taken before and after the experimental group recited verses 195–200 of Surah Al-i Imran aloud. Number, percentage, mean, Pearson correlation, and ANOVA tests were used to evaluate the data. Statistical significance was accepted as p < .05 for all analyses. RESULTS: A significant group-time interaction was found (p < .05). Compared to the passive resting control group, the experimental group showed statistically significant increases in salivary serotonin, dopamine, and NDNF levels, and a significant decrease in cortisol levels. However, a critical dissociation was observed: despite this neuroprotective biomarker profile, the control group reported statistically significantly higher post-intervention mental well-being scores than the experimental group (p < .05). This suggests that the acute cognitive load and performance anxiety associated with the recitation task may temporarily mask physiological benefits in self-reports. CONCLUSIONS: A brief (5-minute) ‘Tartil’ recitation of the Quran demonstrates immediate, positive neurobiological effects by reducing stress hormones (cortisol) and increasing reward- and neuroplasticity-related biomarkers (dopamine, serotonin, NDNF). However, this did not immediately translate to higher self-reported well-being, suggesting the relationship between the neurobiology of recitation and its perceived psychological effects is complex and potentially confounded by factors such as performance anxiety or cognitive load in an experimental setting. CLINICAL TRIAL NUMBER: Not applicable.
Precise Aβ clearance and antioxidant therapy in Alzheimer's disease via photoacoustic imaging-guided palladium hydride nanosheet-mediated photothermal treatment.
Yu L, Zhao M, Zhang W … +7 more , Lv Z, Zhao K, Li H, Qi Y, Peng X, Zheng Z, Zhang W
BMC Neurosci · 2026 Jan · PMID 41612173 · Full text
Inflammation and oxidative stress are critical pathological hallmarks of Alzheimer’s disease (AD). Hydrogen therapy shows promise due to its selective hydroxyl radical (∙OH) scavenging capacity, yet conventional hydrogen...
Inflammation and oxidative stress are critical pathological hallmarks of Alzheimer’s disease (AD). Hydrogen therapy shows promise due to its selective hydroxyl radical (∙OH) scavenging capacity, yet conventional hydrogen delivery fails to effectively accumulate in the brain due to low solubility and rapid diffusion. Here, we report ultra-small palladium hydride (PdH) nanosheets as a dual-functional nanomedicine for AD treatment. The PdH nanosheets exhibit high hydrogen-releasing efficiency via autocatalysis, enabling in situ ∙OH scavenging in the brain. Concurrently, their near-infrared (NIR) photothermal effect, degrading amyloid-β (Aβ) aggregates and transiently enhancing blood-brain barrier (BBB) permeability for improved drug delivery. In AD mice, intravenous PdH treatment combined with NIR irradiation significantly reduced escape latency in the Morris water maze, paralleling reductions in brain Aβ plaques and ROS levels. This study establishes a synergistic strategy of nanoscale hydrogen delivery and photothermal therapy, addressing the dual challenges of BBB penetration and multi-pathology intervention in AD.
Modulating subjective and objective cognitive state fatigue in long COVID with repetitive anodal tDCS: results from a double-blinded randomized controlled trial.
Mischke M, Zaehle T
BMC Neurosci · 2026 Jan · PMID 41580590 · Full text
BACKGROUND: Cognitive fatigue is a frequently reported and debilitating symptom of long COVID, yet effective therapeutic interventions remain limited. Anodal transcranial direct current stimulation (tDCS) over the dorsol...
BACKGROUND: Cognitive fatigue is a frequently reported and debilitating symptom of long COVID, yet effective therapeutic interventions remain limited. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) has been proposed as a promising approach to modulate fatigue-related neural networks. To comprehensively assess cognitive fatigue, the integration of subjective and objective behavioral and electrophysiological measures of induced state fatigue is essential. METHODS: This double-blind, randomized, sham-controlled study investigated the effects of four consecutive daily sessions of 30-minute anodal tDCS over the left dlPFC on subjective and objective markers of cognitive state fatigue in individuals with long COVID. The present paper focuses on secondary outcomes, including subjective state fatigue ratings via visual analogue scales, behavioral performance indices, and electrophysiological markers such as temporal alterations of frontal theta and occipital alpha activity as well as p50 sensory gating. RESULTS: Forty participants received either verum or sham tDCS while completing a gamified adaptive Go/No-Go task. Before and after the stimulation period, cognitive state fatigue was reliably induced using the AX-Continuous Performance Task (AX-CPT). Although tDCS did not significantly affect subjective state-fatigue ratings or behavioral performance, our findings indicate that verum stimulation may stabilize fatigue-related changes in occipital alpha power. No immediate stimulation-related improvements were found in the Go/No-Go task. CONCLUSIONS: These findings indicate that while tDCS may modulate neurophysiological correlates of cognitive state fatigue, its impact on subjective experience and behavioral performance remain limited under the current protocol. These results, however, underscore the importance of including neurophysiological endpoints in intervention research and highlight the need for developing more robust and individualized stimulation protocols. Future studies should consider extended stimulation regimens, alternative task paradigms, and more sensitive behavioral measures to further elucidate the neuromodulatory potential of tDCS in long COVID-related cognitive fatigue. TRIAL REGISTRATION: drks.de Identifier: DRKS00031294, date of registration: 17.02.2023.
Retraction Note: Diabetes mellitus and risk of incident dementia in APOE ɛ4 carriers: an updated meta-analysis.
Rashtchian A, Etemadi MH, Asadi E … +10 more , Binaei S, Abbasi M, Bayani M, Izadi E, Sadat-Madani SF, Naziri M, Khoshravesh S, Shirani M, Anar MA, Deravi N
BMC Neurosci · 2026 Jan · PMID 41530679 · Full text
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Editorial expression of concern: Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage.
Fang JH, Wang XH, Xu ZR … +1 more , Jiang FG
BMC Neurosci · 2026 Jan · PMID 41530667 · Full text
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Exploring extracellular vesicle surface markers and microRNA regulation following remote ischemic conditioning in patients with stroke; a randomized-controlled pilot study.
Best Jensen R, Kjølhede M, Just J … +9 more , Clegg LA, Baek R, Kaadt E, Elfving B, Hess DC, Andersen G, Jørgensen MM, Blauenfeldt RA, Drasbek KR
BMC Neurosci · 2026 Jan · PMID 41526826 · Full text
Remote ischemic conditioning (RIC) has demonstrated neuroprotective effects, yet translating these effects into clinical efficacy has proven challenging. This study aims to uncover the molecular mechanisms underlying RIC...
Remote ischemic conditioning (RIC) has demonstrated neuroprotective effects, yet translating these effects into clinical efficacy has proven challenging. This study aims to uncover the molecular mechanisms underlying RIC’s protective effects, which could potentially identify new therapeutic targets. We conducted the ENOS pilot study, a patient-assessor blinded, Sham-controlled clinical trial, to investigate the molecular changes in patients diagnosed with acute ischemic stroke (AIS). Patients were assigned to undergo either RIC (n = 9), involving five cycles of transient ischemia and reperfusion of the arm, or a Sham treatment (n = 9), using a similar device with less pressure to avoid creating ischemia, within 48 h of symptom onset. We collected plasma samples at three time points: at inclusion (pre-RIC), two hours post-initial RIC, and after seven days, with RIC administered twice daily. Analysis focused on brain biomarkers, specifically extracellular vesicle (EV) surface markers and circulating microRNAs (miRNAs). We identified significant differences in the regulation of CD62 on EVs and five specific miRNAs (miR-374a-5p, miR-20a-5p + miR-20b-5p, miR-19b-3p, miR-24-3p, miR-30d-5p) between the RIC and Sham groups. Notably, miR-374a-5p, known for its neuroprotective properties, was significantly increased in patients treated with RIC (p = 0.015). Furthermore, the changes of several of these miRNAs were correlated with improvements in red blood cell (RBC) deformability and aggregation during shear stress. In addition, we observed significant increases in CD62 on EVs at both the two-hour and 7-day follow-ups in the RIC group. These findings suggest that RIC may induce specific changes in EV surface markers and circulating miRNAs which could serve as future biomarkers for the RIC response. The trial was registered on clinicaltrails.gov (NCT04266639) on February 12, 2020 before trial initation on July 29, 2020.
Oxidative and histopathological changes in the hippocampus and prefrontal cortex following light-at-night and methamphetamine exposure.
Mbagwu SI, Levi UI, Obi NP … +3 more , Chinwuba FE, Anokwa CO, Utopejit UE
BMC Neurosci · 2026 Jan · PMID 41507770 · Full text
BACKGROUND: Methamphetamine (METH) is a potent psychostimulant with neurotoxic effects, while exposure to light-at-night (LAN) disrupts circadian rhythms and contributes to neuronal stress. Both are independently associa...
BACKGROUND: Methamphetamine (METH) is a potent psychostimulant with neurotoxic effects, while exposure to light-at-night (LAN) disrupts circadian rhythms and contributes to neuronal stress. Both are independently associated with oxidative damage and cognitive impairment, yet their combined effects on critical brain regions like the hippocampus and prefrontal cortex remain understudied. This study assessed the oxidative and histopathological alterations in the hippocampus and prefrontal cortex of Wistar rats following combined exposure to METH and LAN. METHODS: Twenty-eight adult male Wistar rats were divided into four groups (n = 7): Group A (Control), Group B (LAN only), Group C (METH only), and Group D (LAN + METH). METH (2 mg/kg body weight) was administered intraperitoneally for 21 days to Groups C and D. For LAN exposure, rats in Groups B and D were subjected to continuous light during the usual dark cycle (18:00 to 06:00) throughout the experimental period. At the end of the study, brain tissues were collected for oxidative stress assays (MDA, SOD, GSH, CAT, and GSH-Px) and histological evaluation. RESULTS: In the hippocampus, MDA levels showed a non-significant increase across groups, while GSH significantly decreased in Groups B, C, and D. SOD decreased in Groups B and C but significantly increased in Group D. CAT activity decreased non-significantly in Groups B and D and significantly in Group C. In the prefrontal cortex, MDA significantly increased in all treatment groups, with a corresponding reduction in antioxidant enzyme levels, particularly GSH and GSH-Px. Histological analysis revealed mild pyknotic cells in LAN-only groups, moderate degeneration in METH-only groups, and extensive neuronal damage such as pyknosis, vacuolations, and disrupted lamination in the combined exposure group for both brain regions. CONCLUSION: Combined METH and LAN exposure causes more severe oxidative stress and neurodegeneration in the hippocampus and prefrontal cortex than individual exposures. This was reflected in higher MDA levels, reduced antioxidant enzyme activities (SOD, CAT, GSH, and GSH-Px), and clear signs of neuronal degeneration, including pyknotic cells, vacuolations, and disorganized cortical layers in both the hippocampus and prefrontal cortex. The findings suggest that exposure to both METH and environmental stressors can work together to worsen oxidative imbalance and neuronal damage. CLINICAL TRIAL NUMBER: Not applicable.
Evaluation of the neuroprotective effects of alpha lipoic acid-loaded folate-conjugated chitosan nanoparticles against 6-OHDA-induced apoptosis and oxidative stress in an in vitro Parkinson's disease model.
Gheybi E, Jalili-Nik M, Hosseinzadeh P … +3 more , Mirzaei SM, AlAlikhan A, Soukhtanloo M
BMC Neurosci · 2026 Jan · PMID 41491116 · Full text
Folate receptors, which mediate the cellular uptake of folic acid (FA) for essential processes such as DNA synthesis and repair, are expressed on neurons affected in Parkinson’s disease (PD). While the etiology of PD rem...
Folate receptors, which mediate the cellular uptake of folic acid (FA) for essential processes such as DNA synthesis and repair, are expressed on neurons affected in Parkinson’s disease (PD). While the etiology of PD remains incompletely understood, oxidative stress is implicated as a key contributor. Alpha-lipoic acid (ALA) is a potent antioxidant; however, its therapeutic application is limited by instability, low bioavailability, and an unpleasant odor. Nanotechnology offers a promising strategy to overcome these limitations. This study aimed to develop and characterize folic acid-conjugated chitosan nanoparticles encapsulating ALA (FA-CS-ALA NPs) and to evaluate their efficacy against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. The FA-CS-ALA NPs, characterized by transmission electron microscopy, exhibited an irregular spherical morphology. Dynamic light scattering (DLS) analysis determined an average particle size of 658.13 nm and a polydispersity index (PDI) of 0.17, indicating moderate size distribution. In vitro studies using SH-SY5Y neuroblastoma cells demonstrated that 6-OHDA exposure significantly increased oxidative stress, neuroinflammation, and apoptosis. Both free ALA and FA-CS-ALA NPs effectively mitigated these deleterious effects. Notably, the FA-CS-ALA NPs exhibited superior neuroprotective efficacy compared to free ALA, suggesting that the folate-conjugated nanocarrier enhances therapeutic delivery.
Neural substrates associated with the acquisition of fine finger force control.
Takahashi A, Ishizaka R, Minami K … +5 more , Tanaka Y, Miyazaki T, Oguma K, Shimizume N, Watanabe T
BMC Neurosci · 2025 Dec · PMID 41390358 · Full text
BACKGROUND: Precise finger force control is essential for performing everyday tasks such as writing, buttoning, and eating. While the neurophysiological basis of cognitive skill learning has been extensively studied, muc...
BACKGROUND: Precise finger force control is essential for performing everyday tasks such as writing, buttoning, and eating. While the neurophysiological basis of cognitive skill learning has been extensively studied, much less is known about the neural mechanisms supporting the acquisition of fine motor skills involving finger force control. This study aimed to investigate changes in cortical oscillatory activity and event-related potentials (ERPs) associated with the acquisition of fine finger force control. RESULTS: Eighteen right-handed healthy young adults practiced a visual target-matching task using a left-hand pinch grip. Force control performance and electroencephalogram (EEG) recordings were assessed before and after training. Behavioral analyses revealed significant improvements in time to target, velocity to target, mean force error, and force variability, with no changes in reaction time. EEG analysis showed enhanced alpha- and beta-band event-related desynchronization after learning. ERP analysis further revealed a significant reduction in N2 amplitude and a significant increase in P3 amplitude following learning. CONCLUSIONS: These results suggest that learning fine finger force control is accompanied by enhanced visuomotor processing, more efficient stimulus discrimination, and greater attentional allocation. This study provides novel insights into the neurophysiological underpinnings of fine motor skill acquisition.
Sex-specific cypermethrin-induced hippocampal neurotoxicity is associated with alterations in signaling molecules for antioxidant defense, membrane integrity, apoptosis, and GABAergic integrity.
Imam A, Busari M, Oyegbola C … +8 more , Moyinoluwa BF, Faith O, Samuel APG, Ibrahim IB, Atiyatul-Hanan GT, Iyiola AM, Ijomone OM, Ajao MS
BMC Neurosci · 2025 Dec · PMID 41388238 · Full text
Cypermethrin(CP), a widely used pesticide, is recognized for its neurotoxic potential. The hippocampus is particularly susceptible to such damage, and sex may influence susceptibility. We investigated sex-specific hippoc...
Cypermethrin(CP), a widely used pesticide, is recognized for its neurotoxic potential. The hippocampus is particularly susceptible to such damage, and sex may influence susceptibility. We investigated sex-specific hippocampal neurotoxicity following short-term CP exposure in rats, focusing on oxidative stress, apoptosis, membrane integrity, and GABAergic interneuron function. Adult male and female Wistar rats (n = 8/group/sex) were orally exposed to corn oil (vehicle control), low (6.25 mg/kg), or high (12.5 mg/kg) doses of CP for 14 days. High-dose CP induced significant weight loss in both males (p = 0.0055) and females (p = 0.0025). CP caused dose-dependent and sex-dependent alterations: females showed greater vulnerability in Na⁺/K⁺-ATPase and COX-2 suppression (treatment × sex interaction, p < 0.05), while males exhibited reduced Nrf2 expression, indicating impaired antioxidant response. Apoptotic markers revealed a distinct pattern; females showed robust Caspase-3 activation alongside increased BCL-2, whereas males displayed a net reduction in BCL-2. Furthermore, CP disrupted parvalbumin-positive GABAergic interneurons, with males showing greater susceptibility to this effect. Collectively, these findings demonstrate that CP induces sex-dependent hippocampal neurotoxicity, with males more vulnerable to oxidative stress and neuronal loss, and females to apoptotic signaling and GABAergic disruption. Understanding such sex-specific vulnerabilities is crucial for risk assessment.
Retraction Note: Cerebrolysin™ efficacy in a transgenic model of tauopathy: role in regulation of mitochondrial structure.
Rockenstein E, Ubhi K, Trejo M … +8 more , Mante M, Patrick C, Adame A, Novak P, Jech M, Doppler E, Moessler H, Masliah E
BMC Neurosci · 2025 Dec · PMID 41382024 · Full text
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Guanidino compounds with native GABA(A) δ receptor selectivity: a tale of homeostatic compensation in δ-KO mice.
Meera P, Uusi-Oukari M, Wallner M … +1 more , Lipshutz GS
BMC Neurosci · 2025 Dec · PMID 41372746 · Full text
Altered GABAergic transmission has been implicated in the neurological symptoms of metabolic disorders associated with guanidino compound (GC) accumulation. Building on previous findings that selected GCs act as direct o...
Altered GABAergic transmission has been implicated in the neurological symptoms of metabolic disorders associated with guanidino compound (GC) accumulation. Building on previous findings that selected GCs act as direct orthosteric GABAA receptor (GABAR) agonists, we now asked whether these GCs act preferentially on high-affinity extrasynaptic δ subunit-containing receptors (δ-GABAs). Using whole-cell patch clamp recordings from mouse cerebellar granule cells (CGCs) in brain slices of wild-type and δ-subunit knockout (δ-KO) mice, together with 5 nM [³H]muscimol displacement assays on WT and δ-KO forebrains, we compared the actions of four structurally GABA-like GCs — guanidinoacetate (GAA), β-guanidinopropionate (β-GPA), guanidinoethanesulfonate (GES), and γ-guanidinobutyrate (γ-GBA). These compounds activated CGC GABARs in cumulative concentration-response curves and displaced the highly δ-GABAR-selective ligand [3H]muscimol suggesting δ-GABAR-selective orthosteric agonist actions. In δ-KO forebrains, total [³H]muscimol binding was reduced by ~ 50%, confirming the loss high-agonist-affinity but low-abundance (~ 5% of total forebrain GABARs) δ-GABARs. δ-KO CGCs showed markedly reduced agonist sensitivity, with EC₅₀ values (µM, WT/δ-KO): GABA (2/6) < β-GPA (3/8) < GAA (4/14) < GES (32/72) < γ-GBA (44/219). The modest loss of agonist sensitivity for GABA and the four GABA-mimetic GCs in δ-KO CGCs is consistent with compensatory upregulation of non-δ extrasynaptic GABARs containing only α and β subunits, as previously described (Tretter et al., JBC 2001), explaining the preserved tonic inhibition in δ-KO neurons. Our findings demonstrate that GABA-mimetic GCs preferentially target δ-GABARs and suggest that homeostatic compensation by αβ-type GABARs is a key adaptive mechanism maintaining inhibitory tone in δ-KO CGC neurons.
Cognitive and neuroanatomical effects of chronic high-fructose corn syrup consumption in the aging rat brain.
Çevreli B, Öztürk G, Baygül O
BMC Neurosci · 2025 Nov · PMID 41315901 · Full text
BACKGROUND: This study aimed to investigate the cognitive and neuroanatomical effects of chronic high fructose corn syrup (HFCS) consumption in aged male rats under different dietary intake levels. MATERIALS AND METHODS:...
BACKGROUND: This study aimed to investigate the cognitive and neuroanatomical effects of chronic high fructose corn syrup (HFCS) consumption in aged male rats under different dietary intake levels. MATERIALS AND METHODS: Thirty-three 15-month-old male Sprague Dawley rats were divided into three groups: a control group (fed 20 g chow/day, n = 11), a pellet-resticted (Per)+HFCS group (11% HFCS solution and fed 10 g chow/day, n = 11), and HFCS group (11% HFCS solution and 20 g chow/day, n = 11). The HFCS groups received an 11% weight/volume HFCS solution for 16 weeks. This study assessed long-term spatial memory retention using an eight-arm radial maze and short-term working memory using a Ymaze. Motor coordination was evaluated through a locomotor activity test. Total brain and hippocampal volumes were analyzed using the ImageJ program. RESULTS: Per+HFCS rats consumed more HFCS and gained more weight than the other groups (p < 0.05). No significant differences were found among groups in locomotor activity or Y-maze performance (p > 0.05). Similarly, there were no significant differences in working memory errors (WME) or reference memory errors (RME) at 48, 72, 96, 120, or 144 hours in the spatial memory assessments of aged rats (p > 0.05). However, the HFCS group completed the eight-arm radial maze faster at 48 hours (p = 0.0467; 95% CI [0.87, 1.18]). No significant differences were observed in hippocampal or total brain volumes between groups (p > 0.05). CONCLUSION: These findings indicate that 11% HFCS consumption at different levels of food intake did not adversely affect learning, memory, or hippocampal and total brain volumes in aged rats. Chronic HFCS intake in late life, regardless of food intake, appeared to have no significant impact on neurocognitive performance. Future studies should further investigate how varying HFCS concentrations influence cognitive function and brain structure in aging models, independent of circadian feeding patterns or total caloric load. CLINICAL TRIAL NUMBER: Not applicable.
The vab-1/Eph receptor and ephrins efn-1 and efn-4 are required for C. elegans chemosensory and thermosensory circuit assembly and function.
Kalichamy K, Arnold M, Hill T … +5 more , Johnson A, McCardel K, Taylor WK, Upton B, Hudson ML
BMC Neurosci · 2025 Nov · PMID 41299233 · Full text
BACKGROUND: The nematode Caenorhabditis elegans displays many distinct behaviors, making it an ideal system to understand the relationship between genes, cells, and behavioral output. In C. elegans, thermal information i...
BACKGROUND: The nematode Caenorhabditis elegans displays many distinct behaviors, making it an ideal system to understand the relationship between genes, cells, and behavioral output. In C. elegans, thermal information is primarily detected by the AFD sensory neurons, with minor input from the AWC neurons. Similarly, ionic solutes such as sodium chloride are detected by the ASE chemosensory neurons. Both sensory neuron pairs synapse primarily onto the AIY interneurons. RESULTS: We show that AIYL/R ventral contact is mediated via the ephrin gene efn-1 in a linear genetic pathway with vab-1. In addition, we show that this activity requires both a VAB-1 kinase-dependent and a kinase independent function. We also show that efn-4 is required for AFD neuron axon extension, and that this strongly correlates with AIY neuron morphology. ASE morphology, however, does not require efn-4 function. In addition, efn-4 is required, in part, for normal synaptic vesicle cluster count in both AFD and ASEL neurons. Finally, we demonstrate that efn-4 is required for normal thermotaxis behavior, and to a lesser degree, salt-dependent chemotaxis, while vab-1 and efn-1 also contribute to normal thermosensory function, albeit to a lesser degree than efn-4. CONCLUSIONS: These data illustrate that left-right circuit connectivity, between the left-right thermosensory neuron pair and/or the left-right first layer interneuron pair, may be required for normal thermotactic responses. These data also highlight the importance of EphRs and ephrins in multiple aspects of sensory circuit assembly and function and suggest that efn-4 may coordinate thermosensory circuit assembly. CLINICAL TRIAL NUMBER: Not applicable.
Changes in EEG and ECG signal connectivity during tilt table testing in healthy young adults without syncope.
Runnova A, Zhuravlev M, Novikov M … +2 more , Borodusova A, Kiselev AR
BMC Neurosci · 2025 Nov · PMID 41225343 · Full text
INTRODUCTION: Tilt table testing (TTT) has been used for over fifty years in clinical and basic medicine to study the adaptation of heart rate and blood pressure to changes in body position. In the area of studying loc...
INTRODUCTION: Tilt table testing (TTT) has been used for over fifty years in clinical and basic medicine to study the adaptation of heart rate and blood pressure to changes in body position. In the area of studying local features of electroencephalogram (EEG) and electrocardiogram (ECG) signal synchronization, there is a lack of research devoted to the precise quantitative mathematical analysis of electrophysiological signals recorded during TTT. Furthermore, most studies related to brain activity analysis focus on the development of syncope. METHODS: This study analyzed electrophysiological signals (EEG and ECG) in 19 healthy men. The TTT procedure was performed in a gentle mode with a slight elevation (45°) of the volunteers after 15 min of horizontal positioning. This procedure eliminated the risk of syncope. Time-frequency analysis of the EEG was performed using a continuous wavelet transform. Synchronization of electrophysiological signals in the brain and cardiac activity was assessed using wavelet bicoherence, assessed pairwise between ECG and EEG signals. RESULTS: EEG activity in the brain remained unchanged before and after verticalization of the volunteers. Heart rate increased, on average, from 1.0 to 1.05 Hz in the horizontal position to 1.3-1.4 Hz in the vertical position (p < 0.005). Significant changes in synchronization were demonstrated before and after verticalization of the volunteers. Most interesting is the increase in ECG and EEG synchronization in the low-frequency range [0.25; 0.75] Hz in response to the tilt table test. Such changes in synchronization can be interpreted in the context of the activation of the human body's adaptive responses during this test. CONCLUSION: This study results provide a basis for understanding the physiological relationship between the cardiovascular system and brain activity during the standing position test (SPT) without syncope. These results suggest that low-frequency (below the baseline heart rate) components of P-QRS-T complex variability may be a promising approach for studying neurocardiac interactions.
Short- and long-term neurobehavioural impairments in mice offspring following chronic perinatal caffeine exposure and withdrawal.
Olopade FE, Folarin OR, Gilbert TT … +1 more , Olopade JO
BMC Neurosci · 2025 Nov · PMID 41219952 · Full text
This study explored neurodevelopmental and adult neurobehavioural outcomes in mouse offspring following chronic perinatal caffeine exposure and subsequent withdrawal. Healthy adult female BALB/c mice were mated and, at g...
This study explored neurodevelopmental and adult neurobehavioural outcomes in mouse offspring following chronic perinatal caffeine exposure and subsequent withdrawal. Healthy adult female BALB/c mice were mated and, at gestational day (GD) 10, were randomly assigned to one of three groups (n = 4): control, low-dose caffeine, and high-dose caffeine. The caffeine-exposed groups received either a low (50 mg/kg) or high (100 mg/kg) dose of caffeine daily via oral gavage from GD 10 until the end of lactation at postnatal day (PND) 21, whereas the control group received sterile water. At PND 21, a subset of offspring from the caffeine-exposed and control groups underwent neurodevelopmental behavioural assessments, including negative geotaxis, cliff avoidance, and surface righting tests, to evaluate the effects of chronic perinatal caffeine exposure on sensorimotor reflex functions. The remaining offspring were allowed to grow into adulthood and, at three months of age, underwent neurobehavioural assessments to evaluate motor function, anxiety-like behaviour, and cognition via the pole test, open field test, and Morris water maze (MWM) test. Compared with those in the high-dose caffeine group, the mice in the low-dose caffeine group had accelerated attainment of neurological milestones, such as the righting reflex and cliff avoidance. Conversely, compared with the control and low-dose caffeine treated offspring, the high-dose caffeine-treated offspring presented delayed eye opening and impaired negative geotaxis. However, there were no significant differences between the caffeine-exposed and control groups in the adult neurobehavioural assessments following caffeine withdrawal. These findings suggest that perinatal caffeine exposure can influence early neurodevelopmental processes but does not seem to have persistent effects on motor function, cognition, or anxiety in adulthood. This study underscores the transient nature of caffeine’s impact on brain development and highlights the need for further research to explore the long-term consequences of prenatal caffeine exposure.
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