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This study aimed to explore the effect and mechanism of polyphyllin Ⅱ in improving di(2-ethylhexyl)phthalate(DEHP)-induced learning and memory impairment. In the experiment, male C57BL/6 mice were randomly divided into five groups: a control group, a model group(exposed to 5 mg·kg~(-1) DEHP), and polyphyllin Ⅱ groups(5 mg·kg~(-1) DEHP + 0.5 mg·kg~(-1) polyphyllin Ⅱ, DEHP + 1 mg·kg~(-1) polyphyllin Ⅱ, and DEHP + 2 mg·kg~(-1) polyphyllin Ⅱ). The learning and memory function of mice was tested using the Morris water maze. The hippocampal neuron structure was detected by Nissl staining. The expression of casein kinase Ⅱ subunit beta(CK2b), protein kinase B(Akt)-cAMP response element binding protein(CREB) pathway-related proteins, as well as postsynaptic density protein 95(PSD95) and synapsin 1 was determined by immunofluorescence and Western blot. The brain-derived neurotrophic factor(BDNF) expression was measured by enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the control group, DEHP induced learning and memory impairment, as well as hippocampal neuronal apoptosis in mice. Additionally, DEHP downregulated CK2b, inhibited the Akt-CREB pathway, and downregulated the PSD95, synapsin1, and BDNF expression. After polyphyllin Ⅱ administration, DEHP-induced learning and memory impairment was significantly improved, with inhibited hippocampal neuronal apoptosis, restored CK2b expression, reactivated Akt-CREB pathway, as well as restored expression of PSD95, synapsin1, and BDNF. Furthermore, the surface plasmon resonance(SPR) experiment of N2a cells demonstrated that polyphyllin Ⅱ targeted CK2b and stabilized its expression. After using siRNA to inhibit CK2b, the neuroprotective effect of polyphyllin Ⅱ was also significantly inhibited, and neuronal apoptosis was reinduced. In conclusion, polyphyllin Ⅱ can ameliorate DEHP-induced learning and memory impairment, with its potential mechanism involving the Akt-CREB pathway activation via CK2b upregulation, which leads to restored PSD95 and synapsin1 expression, and synaptic plasticity, as well as inhibited neuronal apoptosis, ultimately exerting a neuroprotective effect. This study suggests that polyphyllin Ⅱ possesses a neuroprotective effect and has potential application value in improving cognitive impairment. Show less

To synthesise existing research on the impact of gestational diabetes mellitus (GDM) on fetal neural development and subsequent cognitive function in offspring. A systematic review was conducted following PRISMA guidelines. PubMed, Cochrane Library, and ClinicalTrials.gov were searched from January 1964 to October 2024. Studies comparing offspring of mothers with GDM to those without were included. Quality was assessed using the Newcastle-Ottawa Scale (NOS). Seventeen studies met the inclusion criteria. The findings suggest that GDM is linked to subtle yet significant neurodevelopmental modifications, encompassing delays in communication and language proficiency, behavioural dysregulation, as well as heightened susceptibility to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Electrophysiological investigations revealed alterations in cortical activity and extended auditory responses, while neuroimaging studies documented structural variations, including changes in the dimensions of the corpus callosum, ventricular size, and sulcal maturation. Molecular investigations uncovered dysregulated microRNAs that play a role in neurogenesis. Numerous studies emphasised the dose-dependent effects of maternal glucose concentrations and the protective impact of effective glycemic control. Maternal GDM is associated with alterations in fetal brain structure and function, which may predispose offspring to neurodevelopmental risks. While not all deficits persist, these findings highlight the potential value of early glycemic control and postnatal monitoring for at-risk infants. Further longitudinal research is needed to distinguish causal GDM effects from environmental confounders. Show less

Memantine (Mem), an uncompetitive antagonist of the N-methyl-D-aspartate receptor (NMDAr), has demonstrated neuroprotective effects in preclinical stroke models by reducing excitotoxic damage. However, the efficacy of low acute doses administered during the immediate post-ischemic phase remains insufficiently characterized. Male rats underwent permanent middle cerebral artery occlusion (pMCAO) and received a single intraperitoneal dose of Mem (5 mg/kg) two hours post-occlusion. Neurological deficits were assessed using the modified Neurological Severity Score (mNSS). Infarct area and neuronal preservation were quantified using MAP2 immunohistochemistry. BDNF and PSD95 protein levels were measured by ELISA, and their gene expression was evaluated via RT-PCR. Mem treatment significantly reduced infarct area (p = 0.000029) and attenuated neurological deficits (p < 0.0001). MAP2 immunoreactivity was higher in the Mem-treated group (p = 0.000003), indicating preservation of neuronal structure. BDNF protein levels did not differ between the pMCAO and pMCAO+Mem groups; PSD95 protein and its corresponding DLG4 mRNA were increased in the pMCAO group compared with Sham. In the other groups, levels remained unchanged. Early administration of low-dose memantine confers acute neuroprotection after stroke by reducing tissue damage and preserving neuronal integrity, without affecting ischemia-induced BDNF and PSD95 protein and gene expression. These findings suggest a selective early neuroprotective mechanism and highlight the need for long-term and sex-inclusive studies to further evaluate memantine's therapeutic potential. Show less

ObjectiveTo evaluate the effects of a combined psychological and functional exercise intervention on emotion, quality of life, and brain-derived neurotrophic factor (BDNF) levels in patients with Parkinson's disease (PD).MethodsIn this randomized controlled trial, 172 patients with PD were randomly assigned into 2 groups with 86 patients in each group. The control group received routine care, while the intervention group received a 12-week intervention combining psychological support with functional exercise in addition to routine care. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Parkinson's Disease Questionnaire-39 (PDQ-39), Barthel Index, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and serum BDNF levels were assessed before and after the intervention. Adherence rates were also determined for each group. Spearman correlation analysis was used to examine associations between changes in BDNF (ΔBDNF) and changes in HAMA (ΔHAMA) and HAMD (ΔHAMD) scores.ResultsAt the end of the 12-week clinical trial, the intervention group demonstrated significantly lower HAMA, HAMD, PDQ-39, and MDS-UPDRS scores ( Show less

Physical activity triggers complex molecular responses in skeletal muscle, with increasing evidence showing systemic signaling roles for muscle-derived microRNAs (myomiRs). Among these, miR-206 has attracted attention for its dual function: promoting muscle regeneration but potentially harming the central nervous system (CNS). This review examines how miR-206 expression is regulated during exercise and its effects on muscle biology-such as fiber-type specification, mitochondrial changes, and neuromuscular junction (NMJ) repair. It also explores the paradoxical effects of high miR-206 levels in the CNS, where it targets brain-derived neurotrophic factor (BDNF), reducing neuroplasticity and increasing vulnerability to neuropsychiatric and neurodegenerative diseases. The review highlights disease-specific aspects, showing miR-206 as harmful in Alzheimer's, stroke, and depression, but potentially protective in amyotrophic lateral sclerosis (ALS). We discuss its potential as a biomarker and therapeutic target, stressing tissue-specific regulation approaches. Overall, miR-206 plays a key role in muscle-brain communication, with important implications for exercise, aging, and CNS disorders. Show less

The role of chemokines in motor abnormalities (MAs) in first-episode psychosis (FEP) is underexplored. Investigating immune biomarker levels in FEP, their association with MAs, and their differences with individuals without FEP may reveal therapeutic targets. Thirty-eight patients and thirty-four controls were included. Primary outcomes assessed group differences in chemokines related immune whole blood biomarkers, including innate (CCL2, CCL3, and CCL11), compensatory (PPARα, CXCL1, and CB2), natural immune chemotaxis biomarkers (CXCL2 and CXCR4), and growth factors (LPAR2, brain-derived neurotrophic factor [BDNF], and vascular endothelial growth factor [VEGF]). Our secondary aim was to examine their association with the total score of five motor scales: the Neurological Evaluation Scale (NES), Simpson Angus Scale (SAS), catatonia symptom of the Comprehensive Assessment of Symptoms and History (CASH), Barnes Akathisia Rating Scale, and Unified Parkinson's Disease Rating Scale (UPDRS). We found significantly higher levels of protein markers (CCL2, VEGF, and CXCL12) and mRNA expression (CXCR4, PPARα, CB2, and LPAR2) in FEP patients compared to the control group. We only observed positive and significant results for CCL2-UPDRS total and CXCR4-SAS associations in post hoc multivariate analyses (β = 0.401, p = 0.036 and β = 0.58, p = 0.001, respectively). Elevated levels of potential neurotoxic (CCL2) and neuroprotective (PPARα and CB2) biomarkers were seen in FEP patients when compared to controls. Moreover, CCL2 levels seem to be directly associated with Parkinsonism in FEP patients, while CXCR4 may be protective against extrapyramidal symptoms. Further research should clarify immune differences between FEP and non-FEP groups, especially in chemotaxis and endocannabinoid pathways. Show less

The Gold Coast criteria permit diagnosis of amyotrophic lateral sclerosis (ALS) even without upper motor neuron (UMN) signs. However, whether ALS patients with UMN signs (ALSwUMN) and those without (ALSwoUMN) share similar characteristics and prognoses remains unclear. This study compared clinical features, disease progression, electrophysiological findings, biomarker profiles, imaging parameters, and survival between these groups. ALS patients diagnosed according to the Gold Coast criteria were classified into ALSwUMN (n = 51) and ALSwoUMN (n = 20) groups. We evaluated clinical data, motor evoked potentials (MEP), and serum biomarkers, including cardiac Troponin T, neurofilament light chain, glial fibrillary acidic protein, and brain-derived neurotrophic factor. Imaging parameters, including cortical thickness and white matter volume, were also evaluated. Survival was analyzed using the Kaplan-Meier method. The groups showed broadly similar clinical features, disease progression, and biomarker profiles. Abnormal MEPs were more frequent in ALSwUMN (94.0%) than in ALSwoUMN (63.2%, p = 0.017). Both groups demonstrated cortical thinning in the precentral and entorhinal regions compared to healthy controls. ALSwUMN exhibited thinning in the lateral orbitofrontal, insular, and temporal pole regions, while ALSwoUMN showed thinning in the pars opercularis. White matter volume was reduced in both groups in the thalamus, cerebellum, and amygdala, with additional brainstem atrophy in ALSwUMN. No significant survival difference was observed. Despite minor distinctions in electrophysiological and imaging findings, ALSwoUMN had overall comparable clinical profiles and outcomes to ALSwUMN. These findings support recognizing ALSwoUMN within the ALS spectrum under the Gold Coast criteria. Show less

Post-stroke depression (PSD) is a common and clinically significant complication of stroke, associated with worse rehabilitation potential and increased mortality risk. The prevalence of PSD varies from 25% to 59%, depending on the duration of follow-up, peaking in the first years after the stroke event. The pathogenesis of PSD results from a complex interplay of biological and psychological factors, extending far beyond monoamine deficiency. Key roles are played by damage to monoaminergic pathways, neuroinflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, reduced neuroplasticity (including BDNF deficit), and impaired integrity of neuronal networks. The clinical picture is characterized by a complex of affective (apathy, anhedonia), cognitive (executive dysfunction), and dyssomnic disorders. Although selective serotonin reuptake inhibitors remain the first-line treatment, the modern therapeutic approach to PSD requires targeting all components of its pathogenesis. A promising direction is the use of antidepressants with a multimodal mechanism of action, such as the original drug fluvoxamine, which combines serotonergic effects with anti-inflammatory and neuroprotective properties via sigma-1 (σ1) receptor agonism. Optimizing PSD treatment is achievable through the implementation of a personalized approach, including long-term screening and comprehensive management of the identified disorders. Show less