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Niemann-Pick disease, type C1 (NPC1), is a rare, fatal, neurodegenerative lysosomal disorder caused by pathological variants in Proximal Extension Assays (PEA) were used to determine relative protein expression levels from 68 serum samples from NPC1 individuals and 20 age-appropriate control serum samples. Statistical models identified NPC1 disease-specific effects after adjusting for covariates. Selected proteins were orthogonally validated by ELISA and correlated with assessments of both disease severity (Age of Neurological Onset (ANO) and Annual Severity Increment Score (ASIS)) and disease burden (NPC Neurological Severity Score (NSS). Quantifiable data was obtained on 2888 proteins, revealing 186 increased (adjusted log The statistical analysis pipeline developed in this study is flexible and scalable and supports application to high-dimensional proteomic datasets. This study identified and validated serum proteins with altered expression in individuals with NPC1, responded to miglustat therapy, and correlated with disease severity or burden. These proteins may have clinical utility as biomarkers and provide insights into cellular mechanisms contributing to NPC1 disease pathology. NCT00344331 (Registration on 2006-06-23). Show less

Neuroinflammation is a central contributor to Huntington's disease (HD) pathogenesis and represents a promising therapeutic target. Laquinimod, an oral immunomodulator with demonstrated neuroprotective effects in preclinical models, has been investigated as a potential treatment for HD. This review critically appraises its preclinical and clinical evidence. A systematic search (January 2025) was conducted in PubMed, Scopus, Embase, Cochrane Library, and Web of Science using terms including "Huntington's disease," "laquinimod," and "quinoline-3-carboxylic acid." Preclinical and clinical studies evaluating laquinimod in HD were included. Due to heterogeneity, findings were synthesized qualitatively. Of 2638 records identified, 10 studies met the inclusion criteria. Preclinical data showed laquinimod improved motor function, reduced neuroinflammation, and promoted myelination, likely via microglial modulation, NF-κB suppression, and increased BDNF expression. Effects on myelin integrity and inflammatory markers were inconsistent. In vitro studies showed limited, variable cytokine modulation in HD patient-derived cells. Clinical trials did not demonstrate significant improvements in motor or functional outcomes, though one study reported minor cognitive and behavioral benefits. Preclinical evidence suggests laquinimod may modulate motor, inflammatory, and myelination pathways in HD; however, clinical evidence shows no meaningful benefit. Data on long-term safety remain limited. Larger, well-designed trials using standardized biomarkers are needed to clarify its therapeutic potential. Show less

Previous research has indicated the brain-derived neurotrophic factor (BDNF) level is lower in schizophrenia and associated with cognitive impairment. Irisin-BDNF axis may strengthen learning and memory functions. This study examined associations between BDNF, peroxisome proliferator-activated receptor-gamma (PPAR gamma) and irisin with cognitive deficits in schizophrenia. We enrolled 80 patients with schizophrenia and 80 healthy controls (HCs). The enzyme-linked immunosorbent assay (ELISA) method was used for biochemical analysis. The Stroop Test, Trail Making Test (TMT), and Verbal Fluency Test (VFT) were used for cognitive assessment. Statistical analyses included t-tests, correlations, and analysis of covariance (ANCOVA) controlling key confounders. In unadjusted analyses, patients had significantly lower BDNF and PPARγ levels than HCs (ps < 0.001). After controlling for covariates, the difference in BDNF was still significant (F = 11804.71, BDNF demonstrates the most robust association with schizophrenia and cognitive function. The association of PPARγ with schizophrenia is confounded by demographic and metabolic factors, and irisin showed a limited link only to negative symptoms. Not applicable. Show less

Neuroplasticity, the brain's capacity to adapt and reorganize in response to experiences and environmental changes, is fundamental to cognitive aging. As individuals age, cognitive functions such as memory, processing speed, and executive function commonly decline, driven largely by changes in neuroplasticity mechanisms like synaptic plasticity, neurogenesis, and functional reorganization. Synaptic plasticity is a well-established mechanism supporting learning and memory across the lifespan, whereas adult neurogenesis, robustly demonstrated in rodents, remains highly limited and controversial in the adult and aged human brain, with evidence largely restricted to rare post-mortem observations and injury-associated conditions. Functional reorganization allows the brain to adapt to structural changes, helping to preserve cognitive function despite age-related decline. Several factors, including oxidative stress, neuroinflammation, and hormonal shifts, exacerbate the decline in neuroplasticity, accelerating cognitive deterioration. Various interventions, including cognitive training, physical exercise, and pharmacological approaches, have demonstrated the potential to promote neuroplasticity and support cognitive health in aging populations. However, one of the major challenges is tailoring these interventions to the unique needs of individuals, as well as identifying novel therapeutic targets for intervention. To effectively address the cognitive decline associated with aging, future research should focus on developing personalized strategies and innovative techniques to enhance or modulate specific neuroplasticity-related processes under defined conditions in the aging brain. These advancements may provide better tools for delaying, mitigating, or even reversing age-related cognitive decline, improving quality of life for older individuals. Show less

Peripheral nerve injuries (PNI) often lead to long-term functional impairment. Mesenchymal stem cells (MSCs) and cannabidiol (CBD) have shown anti-inflammatory and neuroprotective effects in vitro, which may be relevant for PNI research. The aim of this study was to evaluate CBD-rich cannabis extract’s potential to induce anti-inflammatory and neurotrophic gene expression in equine adipose tissue-derived MSCs (EqAT-MSCs) in an inflammatory in vitro environment. The morphology and metabolic activity of EqAT-MSCs ( Show less

Major Depressive Disorder (MDD) is a debilitating and multifactorial neuropsychiatric condition that significantly contributes to the global burden of disease. Its clinical spectrum encompasses persistent low mood, anhedonia, cognitive decline, neurovegetative disturbances, and suicidality. This review synthesizes current evidence on the neurovascular, neurochemical, genetic, and psychosocial mechanisms underlying MDD. A narrative review approach was employed, incorporating data from peer-reviewed publications retrieved through systematic searches in biomedical databases. Emphasis was placed on recent findings that elucidate the interplay between neurobiological dysfunction and systemic influences in MDD pathogenesis. MDD pathophysiology is intricately linked to dysregulation of monoaminergic neurotransmission, aberrant hypothalamic-pituitary-adrenal (HPA) axis activity, and chronic neuroinflammation. Glial cell impairment, particularly involving astrocytes and microglia, disrupts synaptic homeostasis and neurovascular integrity. Genetic analyses estimate a heritability range of 30-50%, with genome-wide association studies identifying susceptibility loci in synaptic and immune pathways. Epigenetic modifications and perturbations of the gut- brain axis modulate vulnerability and progression. Oxidative stress and attenuated neurotrophic signalling, especially involving brain-derived neurotrophic factor (BDNF), further exacerbate neural circuit dysfunction. Sociodemographic determinants, including sex, psychosocial stressors, and socioeconomic adversity, also shape disease onset and trajectory. Although therapeutic modalities exist, limitations in early detection, treatment response, and long-term remission underscore the need for individualized strategies. Emerging approaches integrating epigenetic biomarkers and systems biology hold potential for precision psychiatry. A systems-level, biopsychosocial understanding of MDD is essential to advance targeted, personalized interventions, ultimately improving clinical outcomes in this complex disorder. Show less

To investigate the therapeutic mechanisms of miR-9-5p-overexpressing human umbilical cord mesenchymal stromal cells (hUC-MSCs) in neonatal rat models of hypoxic-ischemic brain damage (HIBD). Fresh neonatal umbilical cords were collected to isolate and culture human umbilical cord mesenchymal stromal cells (hUC-MSCs). Recombinant adenovirus was used to amplify miR-9-5p and transduce hUC-MSCs, generating miR-9-5p-overexpressing cells. Functional assessments included: ELISA to evaluate secretory function (e.g., neurotrophic and anti-inflammatory factors), real-time cell analysis to measure proliferation capacity, Transwell and Dunn chamber assays to assess chemotactic migration ability. Healthy 7-day-old Sprague-Dawley (SD) rats of both sexes were randomly allocated into four groups (n = 12/group, with 4 rats per group assigned to TTC staining, Western blot, or Morris water maze assay, respectively): Sham-operated control group (mock surgery), Hypoxic-ischemic brain damage (HIBD) model group, miR-9-5p-hUC-MSCs treatment group, and Adenovirus-transduced hUC-MSCs (Ad-hUC-MSCs) treatment group. The HIBD model was induced in groups 2-4. At 24 h post-modeling, 1×10 Spindle-shaped and polygonal adherent cells emerged within 3-5 days following umbilical cord tissue block inoculation, with flow cytometric analysis confirming their identity as mesenchymal stromal cells (MSCs). Compared to the Ad-hUC-MSCs treatment group, miR-9-5p enhanced the secretion of neuroreparative and anti-inflammatory factors (e.g., NGF, BDNF, IL-6) in hUC-MSCs while suppressing pro-inflammatory cytokines (e.g., IL-1, IL-2) (p < 0.05). Furthermore, miR-9-5p significantly promoted hUC-MSCs proliferation and augmented the chemotactic migratory capacity of miR-9-5p-hUC-MSCs. At 48 h post-transplantation in the miR-9-5p-hUC-MSCs group, the sham-operated controls showed no detectable cerebral infarction, whereas the model group exhibited distinct pale infarct foci occupying 33.15% ± 4.38% of total brain volume (vs. controls, p < 0.05), indicating severe cerebral injury. Both miR-9-5p-hUC-MSCs and Ad-hUC-MSCs treatments markedly reduced infarct volumes to 14.85% ± 2.79% and 19.11% ± 4.57%, respectively, with the miR-9-5p-hUC-MSCs group demonstrating a statistically superior therapeutic effect compared to Ad-hUC-MSCs (p < 0.05). Transplantation of either Ad-hUC-MSCs or miR-9-5p-hUC-MSCs significantly improved short- and long-term neurobehavioral outcomes in hypoxic-ischemic brain damage (HIBD) rats. At 48 h post-HIBD induction, upregulated expression of Beclin-2 and Caspase-3 proteins was observed in brain tissue. Notably, these elevated protein levels were attenuated following treatment with miR-9-5p-hUC-MSCs or Ad-hUC-MSCs. MiR-9-5p enhances the secretion of immunomodulatory factors and improves the migratory and proliferative capacities of hUC-MSCs. Overexpression of miR-9-5p promotes in vivo homing of hUC-MSCs, which mitigate cerebral injury and exert neuroprotective and reparative effects through dual mechanisms: modulating immune responses and providing neurotrophic support. Furthermore, hUC-MSCs significantly reduce cerebral infarct volume in hypoxic-ischemic brain damage (HIBD) rats and downregulate levels of apoptotic proteins (Beclin-2 and Caspase-3) in brain tissue, demonstrating potent cerebroprotective effects. Show less

Arterial thrombectomy (AT) is a cornerstone in the treatment of acute ischemic stroke (AIS) due to large vessel occlusion. However, the optimal therapeutic time window and the best management strategy for patients presenting beyond the conventional 4.5-hour timeframe remain areas of active investigation and debate. This retrospective cohort study aimed to analyze the effect of timing of AT on recovery in AIS. We retrospectively analyzed 117 AIS patients admitted between January 2021 and January 2023. Participants were categorized into 3 groups: early AT (onset-to-AT < 4.5 hours), late AT (onset-to-AT ≥ 4.5 hours), and late AT + intravenous thrombolysis (IT). Outcomes compared included clinical efficacy, National Institutes of Health Stroke Scale (NIHSS) scores, serum levels of neurotrophic factors, brain-derived neurotrophic factor, vascular endothelial growth factor, residual stenosis, vessel reocclusion, 3-month mortality, and 1-month complications. The total effective rate was higher in the early AT and late AT + IT groups than in the late AT group. Pretreatment NIHSS scores and serum neurological marker levels were comparable across all groups. After treatment, the early AT and late AT + IT groups showed significantly lower NIHSS scores, higher serum levels of neurological markers, and improved treatment efficiency compared to the late AT group. Prognosis-related markers also indicated better outcomes in these 2 groups. Additionally, complications such as mucocutaneous ecchymosis, gastrointestinal bleeding, and intracranial bleeding were significantly reduced in the early AT and late AT + IT groups. AT within 4.5 hours of stroke onset improves efficacy, reduces neurological injury, and decreases complications. For patients presenting beyond 4.5 hours, combining AT with IT achieves comparable therapeutic benefits. Show less

BackgroundAlthough the molecular basis of Alzheimer's disease (AD) is often studied in Caucasians, its genetic basis in Bangladesh remains elusive.ObjectiveWe explored the association between single-nucleotide variants (SNVs) of Apolipoprotein E ( Show less

The number of people living with Alzheimer's disease (AD) is increasing worldwide as populations age. A hallmark of AD is the accumulation of amyloid-β (Aβ) in the brain, and pathways regulating amyloid-β precursor protein (AβPP) processing are of major interest for disease-modifying and preventive strategies such as exercise. Regular exercise is associated with a reduced risk of AD, potentially through limiting Aβ accumulation, yet the underlying cellular mechanisms remain unclear. Acute bouts of exercise induce the release of circulating signalling molecules that may influence AβPP metabolism. To investigate the effects of exercise on AβPP processing, human induced pluripotent stem cell (iPSC)-derived neurons and astrocytes were treated with serum collected before and immediately after high-intensity exercise. Both healthy control and familial AD (PSEN1 A246E) neurons and astrocytes were independently exposed to 10 % pre- or post-exercise serum for 30 min, after which markers of AβPP processing were quantified. Post-exercise serum contained increased amounts of Lacate, BDNF, IL-6, sAβPPα, and Aβ₁-₄₂, and reduced neprilysin activity (p < 0.05). Treatment with post-exercise serum acutely elevated ADAM10 activity in neurons, which was replicated by spiking lactate in pre-exercise serum. sAβPPα was also increased in PSEN1 neurons following post exercise serum treatment with increased Aβ₁-₄₂ secretion in both PSEN1 neurons and astrocytes (p < 0.05). These findings demonstrate that human post-exercise serum can modulate AβPP processing in iPSC-derived neural cells. This supports the concept that circulating exercise-induced factors can influence neuronal pathways relevant to AD pathology. Show less

Alzheimer's disease (AD) is a progressive disorder that affects the brain and leads to cognitive decline and memory loss, with postmenopausal women being unduly affected. Estrogen is believed to exert neuroprotective effects by influencing amyloid-beta accumulation, tau hyperphosphorylation, oxidative stress, synaptic function, neuroinflammation, and brain-derived neurotrophic factor (BDNF) signalling. This review examines the role of estrogen in AD pathogenesis among postmenopausal women. A systematic literature search was conducted using PubMed, Scopus, and Web of Science. Keywords included "estrogen", "Alzheimer's disease", "neuroprotection", "amyloid-beta," and "BDNF." Inclusion criteria were peer-reviewed studies from the past 10 years focusing on estrogen's effects on AD mechanisms, neurobiology, and therapeutic relevance. Articles were screened by title and abstract. Followed by a full-text review to ensure methodological rigour and relevance. Evidence indicates that estrogen reduces amyloid beta burden, inhibits tau phosphorylation, mitigates oxidative stress, preserves synaptic connectivity, and suppresses neuroinflammation. Estrogen also modulates ApoE-linked lipid metabolism and enhances BDNF signalling, supporting neuronal survival and cognitive resilience. Declining estrogen after menopause increases vulnerability to AD. Understanding estrogen's neuroprotective mechanisms may support targeted therapeutic strategies. Hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs) show potential, but further research is needed to optimise timing, dosage, and patient selection in postmenopausal AD prevention and management. Show less

Non-small cell lung cancer (NSCLC) is characterized by high morbidity and lethality, causing a great physical and psychological burden on patients. Therefore, effective treatment of NSCLC patients is very important. This study analyzes the impact of a nursing intervention of case management combined with cognitive-behavioral therapy on anxiety and depression and quality of life in postoperative NSCLC patients. A single-center, non-randomized controlled study in which 80 NSCLC patients from the Hospital were enrolled from May 2023 to January 2024, and were categorized into case management (CM) and cognitive-behavioral therapy (CBT) groups depending on treatment modalities, with case management care in both groups, and cognitive-behavioral therapy care added to the CM combined with CBT (CC) group. The Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), self-perception burden scale (SPBS), life qualities (QLQ-C30), neurotransmitter levels, and clinical effectiveness were primarily assessed in both groups post-treatment. Secondary outcomes included pain level (VAS score), nursing satisfaction, adverse events, and complications. After treatment, the indicators of both groups were significantly different from those of the pre-treatment. Post-treatment, the CC group demonstrated significantly lower scores than the CM group in HAMA (10.18 ± 2.10 vs. 16.04 ± 3.89), HAMD (11.94 ± 2.91 vs. 16.81 ± 3.19), and SPBS (25.52 ± 3.17 vs. 33.50 ± 5.61) (all P < 0.05). Conversely, the CC group showed significantly higher QLQ-C30 scores and levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF). The nursing intervention of case management combined with cognitive behavioral therapy has a good improvement effect on the anxiety and depression status of NSCLC patients. It can improve the quality of life, which is worth promoting and using in the clinic. Show less

The vital role of brain-derived neurotrophic factor (BDNF) in neuronal development, synaptic plasticity, and neuroprotection has been explored for decades. Therefore, the expression, processing, and signalling activities of this neurotrophin, which is reliant upon TrkB and p75NTR receptors, have been well characterised in both health and disease. This review summarises the latest findings on BDNF dysregulation in neuropathologies. Indeed, across diseases of both the central and peripheral nervous systems, BDNF signalling is frequently disrupted, contributing to neuronal dysfunction and degeneration. Consequently, through direct or indirect enhancement of its expression and/or function, BDNF has proved to be a promising therapeutic target across many neurological conditions. However, the complexity of its regulation and interaction with several different receptors underpins the need for further research to deepen our understanding of BDNF disruption in neuropathologies and to achieve its therapeutic potential. Show less

Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study demonstrates that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) exert profound therapeutic effects in a rat model of moderate-to-severe CP established via bilateral carotid artery occlusion with hypoxia. Intravenously administered hUCMSC-Exos displayed sustained brain retention and significantly restored motor coordination and cognitive function. The recovery was primarily mediated through enhanced remyelination driven by promoted oligodendrocyte maturation and differentiation (elevated oligodendrocyte lineage transcription factor 2 and myelin basic protein). Concurrently, the treatment attenuated key pathological processes involving sustained neuroinflammatory responses (reduced ionized calcium-binding adapter molecule 1, tumor necrosis factor-α, and interleukin-6) while elevating brain-derived neurotrophic factor. Our findings establish hUCMSC-Exos as a promising dual-modality therapy for moderate-to-severe CP, mechanistically linked to robust remyelination and coordinated modulation of core disease mechanisms. Show less

Alzheimer's disease (AD) is a common dementia in the elderly population, typically manifested through symptoms of cognitive impairment (CI) and memory loss. Pathologically, it is characterized by abnormally elevated levels of amyloid-β (Aβ) deposition and tau phosphorylation. Given the rapid rate of population aging, many scientists are investigating AD, focusing on its pathogenic mechanisms and potential treatments. Unfortunately, to date, no highly effective therapeutic strategies have emerged. Intriguingly, multiple studies have revealed alterations in the gut microbiome of individuals with AD, suggesting it may serve as a novel avenue for investigating AD pathogenesis. Show less

Alcohol use disorder (AUD) is a significant medical problem and there is great need for developing effective treatment strategies. Brain-Derived Neurotrophic Factor (BDNF) has been shown to play a role in regulating numerous pharmacological and motivational effects of alcohol. We have shown that chronic alcohol-induced escalation of drinking is accompanied by a deficit in BDNF levels in medial prefrontal cortex (mPFC). This study examined whether exercise (wheel-running) attenuates excessive alcohol drinking via increased BDNF expression, thereby mitigating the deficit in mPFC. Adult male C57BL/6J mice were given scheduled (2-hr/day) access to a running wheel in the home-cage 1-hr following opportunity to drink alcohol for 2-hr/day. After six weeks, mice were further separated into groups that received chronic alcohol vapor or control (air) inhalation exposure. Results indicated that alcohol consumption did not alter wheel-running and exercise did not alter alcohol intake during the 6-week baseline. Exercise increased BDNF mRNA and protein expression in mPFC, reversed chronic alcohol-induced reduction in BDNF levels, and attenuated escalated alcohol drinking. Systemic administration of a TrkB receptor antagonist (ANA-12) reversed the beneficial effects of wheel-running in the model. Together, these data provide support for exercise as a potentially effective intervention strategy for treating AUD. Show less

Anorexia nervosa (AN) is a debilitating, often lethal, restrictive-type eating disorder without an effective cure. The underlying neural basis of AN has remained elusive without an animal model that has represented all typical AN symptoms. Here we show that aberrant activation of mediobasal hypothalamic (MBH) glutamatergic neurons led to lethal self-starvation, hyperactivity, anhedonia, social phobia, and increased anxiety, all of which represent typical symptoms of AN. These symptoms were selectively exhibited by targeted activation of MBH neurons expressing steroidogenic factor (SF1) and estrogen receptor alpha (ERa). Moreover, the elicited AN symptoms by activation of MBH glutamatergic or SF1/ERa neurons were rescued by removing release of glutamate or brain-derived neurotrophic factor (BDNF) from these neurons. Importantly, BDNF overexpression in SF1/ERa neurons promoted typical AN symptoms, which were suppressed by removing glutamate release. Thus, our findings identify aberrantly enhanced BDNF and consequent augmented glutamate release from SF1/ERa neurons as a neural basis underlying AN. Show less

The laminins are a family of extracellular matrix proteins that regulate numerous cellular processes, including adhesion, neurite outgrowth, and axon guidance. However, it remains unclear whether laminin regulates axon guidance through local translation. Here, we show that laminin is necessary for local translation in axonal growth cones. Local translation is significantly increased in growth cones of embryonic day 17 mouse cortical neurons, either cultured on or acutely stimulated with soluble laminin 111, in the presence of BDNF. When cultured on laminin isoforms 211 or 221 in the presence of BDNF, there was a remarkable decrease in local translation in growth cones. Using a puromycin-proximity ligation assay to examine newly synthesized β-actin specifically, we find a significant increase in growth cones of neurons cultured on laminin 111 in the presence of BDNF. However, soluble laminin 111 alone results in a significant reduction in nascent β-actin protein synthesis. These results indicate that laminin isoforms can act in multiple ways, including synergistically with guidance cues and independently, to modulate local mRNA translation, thereby differentially influencing axon growth and guidance during development. Local translation in axons is critical for axon guidance. Laminin, a key component of the extracellular matrix, is necessary to induce local translation and thus mediate axon growth and guidance. Show less

Yoga is increasingly incorporated into clinical practice for managing a wide range of mental and physical health conditions, especially those related to stress, and has shown beneficial effects on inflammatory processes and neuroendocrine regulation. Its influence on cytokines such as interleukin-6 and tumor necrosis factor-α, as well as its modulatory action on the hypothalamic pituitary adrenal axis, suggests a potential role in reducing systemic inflammation and improving stress resilience. Despite these promising indications, there is limited scientific evidence from India evaluating yoga's impact on biological markers of stress and inflammation. The present study was undertaken to assess the effects of a structured yoga program on selected biomarkers in 60 adult volunteers who underwent evaluations before and after 3 months of practice. The intervention consisted of a daily 1-h yoga session conducted 6 days a week and included postures, breathing practices, and relaxation techniques. Assessments focused on brain-derived neurotrophic factor, interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein, cortisol, and perceived stress levels. Findings indicated an increase in brain-derived neurotrophic factor and reductions in inflammatory markers, cortisol, and perceived stress. These outcomes suggest that regular yoga practice can positively influence neurotrophic activity, reduce inflammation, and lower stress, supporting its value as a complementary approach to improving overall health and well-being. Show less

Mental illness conditions and neurodegenerative diseases are an emerging worldwide burden, with depression affecting over 300 million people and dementia cases projected to triple by 2050. Oxidative stress and inflammation are central mechanisms for neuronal injury and cognitive impairment. This review discusses the neurotherapeutic promise of egg-derived antioxidants. Importantly, yolk in polypeptide complex (isolated from egg yolk with immunoglobulin Y) enhances cognitive function by upregulating brain-derived neurotrophic factor via cAMP/PKA and PI3K/Akt signaling. We discuss their molecular modes of action such as reactive oxygen species scavenging, regulation of inflammatory cytokines, maintenance of mitochondrial function, and promotion of neurogenesis and synaptic plasticity. Further, bioavailability, allergenicity, and targeted delivery issues across the blood-brain barrier are addressed in light of progress in nanocarrier systems and encapsulation methods. Comparative observations with other diet-based antioxidants like curcumin, polyphenols, and omega-3 fatty acids are presented to put egg-derived compounds into perspective within the overall nutraceutical regime. Lastly, future directions highlight the importance of targeted clinical trials, regulatory factors, and inclusion in public health initiatives designed to prevent cognitive degeneration and mental illness through accessible nutritional interventions. This review highlights the promising potential of antioxidants derived from eggs as adjunctive neuroprotective therapy and indicates the need for interdisciplinary investigations to extend these findings into the clinic. © 2026 Society of Chemical Industry. Show less

The accumulation of CAG nucleotide duplicates in the huntingtin (HTT) gene triggers a neurological ailment described as Huntington's disease (HD), which is an irreversible, progressive, and inherited condition and affects both motor and cognitive abilities, resulting in a range of symptoms, including irregular gestures (chorea, dyskinesia), psychological disorders, and advanced dementia. Agomelatine is a novel antidepressant and melatonin analog. It exerts a synergistic pharmacological mechanism, combining stimulation of both MT1/MT2 melatonergic receptors with inhibition of 5-HT2C receptors. It was evaluated for its potential neuroprotective impact against HD triggered by 3-nitropropionic acid (3-NP) in rats. Four groups were established using a total of 40 rats: Group I (CTRL), Group II (AGO), Group III (3-NP), and Group IV (AGO + 3-NP). Deficits in motor function provoked by 3-NP were alleviated by agomelatine, as evidenced by increased ambulation and rearing frequencies, alongside a notable decline in immobility time of the open field assessment, elevated final falloff time of the rotarod assessment, and improved grip strength. Agomelatine also improved synaptic plasticity and neuronal survival by optimizing the expression and activity of the BDNF/TrKB/PI3K/AKT pathway and inhibiting apoptosis, microglial, and astrocytic activation. Furthermore, agomelatine administration reduced the expression of ROCK1, suppressing the release of inflammatory responses. Finally, agomelatine possessed neuroprotective activity, as proved by enhancing motor activity and histopathological abnormalities via improving the BDNF/TrKB/PI3K/AKT survival cascade and suppressing the ROCK1 inflammatory pathway. Show less

This study aimed to investigate changes in brain structure and function of hippocampus in aged type 2 diabetes mellitus (T2DM) rats and the effects of tea polyphenol (TP) intervention using magnetic resonance imaging (MRI) and tissue-level molecular analyses. Rats were randomly assigned to six groups: Control, Aged, Aged T2DM, Aged T2DM + TP, Aged T2DM + rosiglitazone, and Aged T2DM + piracetam intervention groups. Anxiety- and depression-like behaviors were assessed using the open field test, the forced swimming test and elevated plus maze. Brain structure, blood flow and neuro-associated metabolites were evaluated via MRI. The number of nerve cells, neurons, microglia and astrocytes, the expression of BDNF/CREB/p-CREB protein, the levels of inflammatory factors, and the integrity of the myelin sheath in the hippocampus were evaluated. Relationships between behavioral, cellular and molecular changes and MRI-derived indicators were evaluated by Pearson correlation analysis. Aged T2DM rats exhibited severe anxiety- and depression-like behaviors accompanied by brain atrophy, reduced blood flow and decreased brain metabolites. At the microstructural level, the number of hippocampal neurons in the Aged T2DM group was significantly reduced, accompanied by increased counts of microglia and astrocytes. Meanwhile, the expression levels of hippocampal p-CREB and BDNF were decreased, the concentration of the inflammatory factor IL-1β, IL-6, TNF-α was elevated, and myelin integrity was impaired. Intervention with TP alleviated anxiety- and depression-like behavior, with MRI-detected abnormalities and in vitro histopathological molecular changes improved (except for myelin integrity). TP intervention mitigated alterations in brain structure and function as well as anxiety and depression-like behaviors in aged T2DM rats. Show less

Hypertension is a multifactorial condition of unknown cause that affects more than 1.28 billion adults worldwide and impacts the sexes differently. The hypothalamic paraventricular nucleus (PVN) plays a central role in blood pressure (BP) regulation by modulating sympathetic tone and releasing neuropeptides that affect the cardiovascular function. In this study, we investigated the transcriptomic profile of the PVN in hypertensive strains and across sexes, aiming to identify novel sex-specific molecular pathways involved in the regulation of BP. To accomplish this goal, we sequenced RNA from the PVNs of normotensive Wistar rats and Spontaneously Hypertensive Rats (SHR), both male and female. We also performed a cardiovascular assessment based on blood pressure (BP) measurements and their variability. Cardiovascular assessment revealed higher SBP in SHRs than in Wistar rats; while males exhibited greater autonomic regulation associated with vasomotor and neurohumoral mechanisms, while females maintained comparable SBP levels primarily through an increase in heart rate, reflecting distinct autonomic adaptations. Hypertension also impacted gene expression, with influences from both the hypertensive state and sex. Compared with female SHRs, male SHRs presented a marked increase in differentially expressed genes (DEGs). Key upregulated genes in males, including Brain-Derived Neurotrophic Factor (Bdnf) and Hypocretin (Hcrt), have already been linked to elevated BP, and Angiotensin II Receptor Type 1 (Agtr1a) is possibly associated with increased SBP-VLF variability, which serves as an indirect measure of enhanced sympathetic tone. In contrast, the female transcriptomic signature was characterized by the upregulation of anti-inflammatory pathways, with upregulation of NLR Family CARD Domain Containing 3 (Nlrc3) and Paired Ig-like Receptor B (Pirb), and downregulation of Absent in Melanoma 2 (Aim2), and S100 Calcium Binding Protein B (S100b). Notably, genes associated with neuroinflammation, such as the downregulation of Annexin A1 (Anxa1) and the upregulation of Solute Carrier Family 11 Member 1 (Slc11a1), were consistently altered in both sexes. These results provide new insights into the cardiovascular and molecular basis of sex differences in hypertension, suggesting distinct neurohumoral autonomic profile in males, whereas in females a greater anti-inflammatory component. These findings offer a valuable framework for developing future sex-specific therapeutic strategies. Show less

Prenatal stress, including maternal immune activation (MIA), affects cognitive performance in the offspring. Since insulin could improve cognitive function in several aspects, we hypothesized that intranasal insulin would attenuate MIA-induced learning and memory deficits. In the present study, the pregnant Wistar rats received lipopolysaccharide (LPS, 250 µg/kg) intraperitoneally on gestational day 15. Intranasal insulin (2 IU, 7 days) was administered to male pups from PND 34-47. During late adolescence, the Morris Water Maze and in vivo electrophysiological recording were performed in male rats to assess spatial learning and memory and long-term potentiation (LTP), respectively. Also, the hippocampal expression of BDNF and PSD-95 was evaluated using real-time PCR. Our results demonstrated that MIA impaired spatial learning and memory in the male pups. Hippocampal synaptic plasticity was also impaired in the adolescent male rats. However, intranasal administration of insulin could overcome MIA-induced impairments and improve learning, memory, and synaptic plasticity in the male pups. Although BDNF and PSD-95 levels were not altered in the hippocampus of MIA pups, intranasal insulin increased PSD-95 expression. Taken together, these findings suggest that intranasal insulin promotes cognitive performance in MIA-exposed pups during adolescence; however, the underlying molecular mechanisms remain to be elucidated. Show less

Intracerebral hemorrhage (ICH) is a destructive cerebrovascular disease, whose secondary injury can trigger severe neuroinflammatory responses. Resolvin D1 (RvD1), as an endogenous specific pro-resolving mediator, has been demonstrated to possess significant anti-inflammatory effects. However, how brain networks relate to RvD1 biosynthesis and the therapeutic potential of RvD1 in post-hemorrhagic repair processes within the brain remain unclear. Serum RvD1 levels were measured at admission and discharge in 40 ICH patients, and their correlation with neurological functional outcomes was analyzed. Combining neuroimaging and Mendelian randomization, we investigated the association between brain network integrity and genetically predicted plasma RvD1 levels. Network pharmacology identified key targets, and an oxyhemoglobin-induced BV2 microglial model validated RvD1's BDNF-dependent anti-inflammatory and anti-apoptotic effects. Serum RvD1 levels decreased from admission to discharge during recovery, with significant correlation between its changes and neurological improvement. Neuroimaging and MR analysis revealed that brain network integrity is significantly associated with genetically predicted plasma RvD1 levels, partially explaining interindividual prognostic variation. Mechanistically, RvD1 modulates microglial metabolism, alleviates oxidative stress, and promotes anti-inflammatory polarization involving the BDNF/AKT signaling network. Genetically predicted plasma RvD1 levels correlate with macro-level brain network integrity while simultaneously promoting micro-level neural repair. This approach overcomes limitations of previous single-pathway or static indicator studies, offering novel biomarkers and intervention strategies with predictive and therapeutic potential for ICH. Show less

We aim to verify clinical (depressive symptoms, rates of psychiatric admissions, and suicide attempts) and neurobiological (Brain-Derived Neurotrophic Factor - BDNF) changes in outpatients with depression undergoing evidence-based psychotherapies (EBP) over a 6-month follow-up. Longitudinal, naturalistic, prospective study, with 47 outpatients undergoing EBP, and 48 healthy controls (HC) for the BDNF levels comparisons. Data were collected at baseline and 6-month follow-up. Statistical analysis was performed using a paired t-test and a multiple linear regression model. BDI scores did not differ between baseline and 6-month follow-up (p = 0.253), and the rates of hospitalizations and suicide attempts at 6-month follow-up were 4.2% (2 cases reported). All patients were using psychotropics. BDNF levels at baseline and after 6-month follow-up did not vary significantly in the patient group (p = 0.314). There was no difference between patients' BDNF levels at baseline and HC BDNF levels (p = 0.211) and between patients' BDNF levels at 6-month follow-up and HC BDNF levels (p = 0.772). Using a mood stabilizer increased the BDNF levels. BDNF levels remained stable. Adding psychotherapy to medication may be associated with low rates of suicide attempts and psychiatric admissions in our sample. Our findings reinforce the importance of combined treatment in preventing adverse outcomes in naturalistic settings. Evidence supports the clinical effectiveness and economic efficiency of psychotherapy for patients with mental disorders, suggesting that outpatient psychotherapy can benefit healthcare systems and patients. Our findings corroborate the literature and reinforce the importance of psychotherapy associated with pharmacotherapy (combined treatment) to prevent outcomes such as further hospitalizations and suicide attempts, even in individuals with a history of severe psychiatric conditions. Research on how psychotherapy works, in terms of psychological mechanisms and its underlying effects on biological processes, is crucial. Scientific evidence makes it possible to include psychotherapies in public health policies worldwide, benefiting individuals suffering from mental disorders. Evidence from naturalistic designs is scarce in the literature. Show less