Gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), mediate critical reproductive functions via the hypothalamus-pituitary-gonadal axis. Their levels fluctuate across the lifespan, particularly during puberty and menopause, and across the menstrual cycle. In addition to peripheral expression, gonadotropin receptors are widely expressed in the brain, notably in memory-associated regions such as the hippocampus and cortex. Alterations in FSH and LH during reproductive transitions correlate with structural and functional brain changes. Puberty disorders, including central precocious puberty (CPP) and congenital hypogonadotropic hypogonadism (CHH), show altered gray and white matter and functional connectivity in the default mode network (DMN), which supports memory and is disrupted early in Alzheimer's disease (AD). Although preclinical evidence implicates gonadotropins in amyloid and tau pathology, studies of attention and memory have yielded inconsistent results. However, reproductive disorders such as primary ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are associated with deficits in cognitive performance, altered DMN dynamics, and increased AD risk. Menopause, characterized by marked gonadotropin elevation, is also accompanied by alterations in brain structure, connectivity, amyloid and tau deposition, and cognition, with associations with FSH and LH that are underexplored. This review synthesizes a broad range of basic and clinical evidence across reproductive transitions and disorders, highlighting shared and distinct mechanisms by which gonadotropins influence brain development, aging, and AD risk, and suggesting directions for future research.
Parkinson's disease (PD) is a neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to significant motor dysfunction. Current treatments stabilize dopamine levels but fail to address underlying neuronal apoptosis, highlighting the need for novel approaches. Although chrysoeriol, a 3'-O-methoxy flavone and luteolin derivative, is well-documented for its anti-cancer, anti-diabetic, antioxidant, and anti-inflammatory properties, its neuroprotective potential in PD, particularly in vivo, remains largely unexplored. This study fills a critical gap by being the first to systematically assess chrysoeriol's neuroprotective effects in a PD mouse model. We evaluated the effects of 5 mg/kg chrysoeriol administered intraperitoneally (IP) for 14 days in an acute 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. Behavioral tests showed notable recovery, as chrysoeriol eliminated deficits in motor function, coordination, and balance, as assessed by the pole test, forced swim test, and tail suspension test. It also mitigated exploratory and locomotor deficits in the open field test, and the Y-maze test revealed improved spatial and learning memory. Hematoxylin and eosin staining indicated a significant reduction in neuronal damage across key brain regions. qPCR analysis showed reduced 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity, downregulation of α-synuclein, and an improved Bcl-2/Bax ratio. These findings suggest chrysoeriol may protect against MPP+-induced apoptosis in mice, potentially via the PI3K/Akt signaling pathway, and reduces mitochondrial damage by downregulating α-synuclein.
Chronic Traumatic Encephalopathy (CTE) is a progressive neurodegenerative tauopathy associated with repetitive head impacts (RHI), yet it remains diagnosable only at post-mortem. Tau, a microtubule-associated protein, normally stabilizes neuronal microtubules and regulates cytoskeletal dynamics. Mechanical strain from RHI is thought to disrupt calcium homeostasis and kinase-phosphatase balance, driving hyperphosphorylation and phosphorylated-tau (p-tau) formation. This results in detachment from microtubules and subsequent p-tau aggregation. These mechanically-induced biochemical changes produce CTE's characteristic lesion: perivascular p-tau deposition in the depths of cortical sulci, reflecting the non-uniform mechanical loading experienced by brain tissue following head impacts. Advances in molecular neuropathology have revealed that CTE tau filaments adopt a unique conformational fold, and that early tau species may contribute to neurotoxicity. Despite this growing understanding, antemortem diagnosis remains challenging. Structural MRI demonstrates frontotemporal atrophy and white-matter abnormalities in impact-exposed individuals, but these findings lack disease specificity. Tau-PET tracers developed for Alzheimer's disease (AD) show limited affinity for the distinct CTE tau fold, while fluid biomarkers variably reflect cumulative exposure but cannot yet discriminate CTE from other tauopathies. Future progress will depend on mechanistically informed diagnostic tools, including conformation-specific biomarkers and PET radiotracers tailored to CTE-specific tau. Multimodal approaches integrating neuroimaging, molecular profiling, exposure metrics, and computational modelling will be essential for early detection, disease monitoring, and informed public health policy around repetitive head impacts.
Prenatal stress affects offspring development. The placenta, an important maternal-fetal mediator, is susceptible to prenatal stress, and its biology affects fetal neurodevelopment, particularly ventral forebrain. Ventral forebrain developmental disruption is linked to neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Currently, multiple mouse models are used to study these links. However, each model may induce unique effects in both placental and neurodevelopmental outcomes, which are rarely studied. To explore this, pregnant mice were exposed 3 times daily to one of three stress models: repeated restraint stress (RS), chronic unpredictable stress (CUS), or repeated footshock stress (FS) beginning at embryonic day (E)12. At E14 or E18, placenta and embryonic brain were collected, and qPCR and brain stereological measurements were performed. Placental immune and ventral forebrain GABAergic gene expression was impacted more at E14, with many changes not apparent by E18, suggesting an acute dysregulated state. Different models had both unique and overlapping effects. E18 analyses suggested adaptation to stress over time, with overall suppression or lack of placental immune factor changes, fewer deviations in the brain, and correlations between placenta and brain, particularly in females. Chronic unpredictable stress showed the most changes at E18. These findings suggest that, while each model has unique effects, as stress exposure progresses, placental immune functioning may promote the normalization of brain GABAergic systems, particularly in females. Further understanding the placenta-brain axis may be valuable in delineating mechanisms that increase and decrease risk of neurodevelopmental disorders.
Neurological disorders (NDs) are a leading global cause of disability and mortality, with their burden falling disproportionately on low- and middle-income countries (LMICs). Pakistan exemplifies the systemic challenges faced in resource-limited settings, including delayed diagnosis, limited specialist access, and fragmented care pathways. Despite this, comprehensive spectrum-based data remain scarce. This study was aimed to quantify the burden and characterize the spectrum of NDs presenting to a major Pakistani tertiary-care center and to identify associated predictors and geographic disparities. A hospital-based crosssectional study was conducted from May 2023 to January 2024, enrolling 537 consecutive patients with confirmed NDs. Descriptive statistics and logistic regression models were employed. Neurodevelopmental disorders were most frequent (31%), followed by neurovascular (20%), epilepsy (14%), autoimmune neurological disorders (12%), neurodegenerative (8%), neuroinfectious (7%), and neuromuscular disorders (6%). Logistic regression revealed strong age- and sex-dependent patterns, including markedly higher odds of neurodegenerative disorders in males and increased odds of neurovascular disorders with older age. Geographic analyses demonstrated a high burden of autoimmune and neuromuscular disorders among patients traveling >100 km, particularly from Khyber Pakhtunkhwa (KPK) and Azad Jammu Kashmir (AJK), highlighting significant access inequities. This study provides comprehensive clinical snapshot of NDs in Pakistan, revealing distinct epidemiological patterns shaped by socioeconomic disparities, geographic inequities, and genetic factors, such as consanguinity. The findings underscore the urgent need for strengthened neurological services, decentralization of specialized care, improved diagnostic capacity, early-interventions, and national surveillance systems. Lessons from Pakistan mirror broader challenges across LMICs and highlight the global imperative to invest in equitable neurological healthcare.
Neurological disorders pose a major public health challenge worldwide, with neuroimmune interaction emerging as a core regulatory mechanism underlying their pathogenesis. This review highlights the progression from static association to dynamic mechanisms between neuroimmune interaction and neurological diseases, filling the research gap in immune function changes during development and aging. We propose a triple regulatory logic framework, including multicellular crosstalk network, context-dependent signaling pathway switching, and host microenvironmental state, which clarifies the bidirectional regulatory patterns of neuroimmune interaction in physiological neurodevelopment and pathological neurodegeneration. Specifically, the neuroimmune system maintains central nervous system (CNS) homeostasis through four core processes during development, while its dysfunction drives chronic neuroinflammation and neurodegeneration via cascading pathological mechanisms. We further discuss clinical translation bottlenecks and targeted intervention strategies based on this framework, providing a theoretical basis for constructing a stage-specific neuroimmune interaction and regulation theory. This review offers new insights into the pathogenesis of neurological diseases and potential therapeutic targets for clinical practice.
Five different homozygous PTRHD1 mutations, two of them in more than one family, have been reported as responsible for intellectual disability (ID) and parkinsonism. In all 10 families, onset of ID was early childhood, and in parkinsonism, later childhood to the fourth decade. We report on a family with four siblings presenting with mild to moderate ID and mildly ataxic gait without spasticity or hemiparesis that is not consistent with parkinsonism. The signs of parkinsonism such as bradykinesia, tremor, slow to response, dementia, and gait problems appeared in the fourth decade. There was no muscle rigidity and postural instability, but there were unusual features of exotropia, pectus excavatum, and prominent clavicles. Linkage analysis using SNP genotyping followed by exome sequencing led to the discovery of PTRHD1 c.155G>A (p.Cys52Tyr), already reported in an Iranian sibling pair. Our findings reveal that not all PTRHD1 mutations manifest with muscle rigidity and postural instability and confirm that gait problems may not be evident until towards the end of the fourth decade. Early onset behavioral problems in presented patients include attention deficit, hyperactivity, aggressive behavior and seclusion, apraxia of speech, stuttering, and somniloquy. Gait ataxia, exotropia, pectus excavatum, and prominent clavicles further widen the clinical phenotype. PTRHD1 is expressed in many organs, and we found widespread expression in the adult brain. The association of PTRHD1 dysfunction with both cognitive and motor phenotypes highlights the potential role of the protein in neurodevelopment and neurodegeneration.
Spinal dysraphisms are a heterogeneous group of congenital spinal cord anomalies resulting from defective neurulation. They include both open and closed forms, with spina bifida (SB) being the most clinically recognized. These conditions frequently coexist with other anomalies, such as syringomyelia and diastematomyelia, significantly complicating clinical presentation and management. We report the case of a male neonate born at term with a lumbar spinal defect consistent with SB occulta. Initial evaluation revealed a closed, skin-colored lesion with preserved neurological function. Early spinal magnetic resonance imaging (MRI) showed vertebral arch defects, a dorsal cystocele and syringomyelia at the L1-L2 level. The patient underwent early neurosurgical repair of SB at 5 days of age, followed by cyst drainage at 1 year of age when lower extremity weakness developed. Subsequent imaging revealed persistent syringomyelia and diastematomyelia, necessitating additional surgical intervention for spinal cord mobilization. The coexistence of these complex anomalies required multiple staged interventions and close longitudinal monitoring. Complex spinal dysraphism demands a multidisciplinary approach with early surgical management and long-term follow-up to prevent neurological deterioration. This case reinforces the importance of timely diagnosis and staged surgical intervention in improving patient outcomes.
Astrogliosis is characterized by an abnormal increase in the number of astrocytes in the brain due to damage, trauma, infection, ischemia, stroke, autoimmune responses, or neurodegenerative disorders. Glial Fibrillary Acidic Protein (GFAP) is a marker for astrocyte development and astrogliosis. Flavonoids have unclear anti-neuroinflammatory effects in astrogliosis. This computational analysis was the first to investigate the potential interaction between flavonoids and the transcription factors involved in GFAP expression. Using AutoDock Vina, 60 flavonoids with known anti-inflammatory properties were docked to 26 proteins involved in GFAP expression. Toxicities of the flavonoids were predicted using the ProtoxII server, and drug-likeness and pharmacokinetic properties were assessed using the DruLiTo and pkCSM software, respectively. BIOVIA Discovery Studio software was used to evaluate the interactions between flavonoids and target proteins. Among the studied flavonoids, biochanin A, bavachin, apigenin, epicatechin, wogonin, kaempferol, hispidulin, genistein, farrerol, diosmetin, and daidzein displayed drug-like properties, no toxicity, favorable pharmacokinetic properties, and better docking scores for Janus Kinase 1 (JAK1), Janus Kinase 2 (JAK2), I Kappa B Kinase (I-κKB), Serine/Threonine Kinase (AKT), and Histone Acetyltransferase (P300). This in silico study revealed that predictive associations between flavonoids and JAK1, JAK2, I-κKB, AKT, and P300 might affect both GFAP expression and the astrogliosis process via the Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) and Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway. The interactions between flavonoid(s) and predicted binding partner(s) were confirmed based on previous studies. These predictive associations are extremely valuable for developing nutritional guidelines and for improving flavonoid-based therapeutic strategies for neurological disorders driven by astrogliosis. This research provides insight for further in vitro and in vivo research.
Multiple sclerosis (MS) is a chronic demyelinating disease and a leading cause of disability in young adults. Its pathophysiology involves complex genetic and immunological mechanisms, among which the suppressors of cytokine signaling (SOCS) proteins play a critical role. These intracellular regulators control cytokine-mediated JAK/STAT signaling, thereby modulating immune activation. In particular, SOCS1 and SOCS3 inhibit key cytokines such as IL-2, IL-12, IL-6, and IL-23, preventing excessive Th1/Th17 responses and neuroinflammation. Dysregulation of SOCS expression or function can favor persistent immune activation and contribute to central nervous system demyelination. MicroRNAs (miRNAs), small non-coding RNAs that repress gene expression post-transcriptionally, have emerged as important modulators of immune regulation. Several miRNAs target SOCS transcripts, influencing their expression and, consequently, cytokine signaling. Altered miRNA profiles have been reported in autoimmune and neurodegenerative diseases, highlighting their potential relevance in MS pathogenesis and as biomarkers. This review summarizes current evidence on SOCS1 and SOCS3 in MS and examines their regulation by miRNAs. In addition, we present a hypothesis-generating in silico analysis identifying candidate miRNAs with predicted interactions with SOCS genes. These computational findings are intended to support and prioritize potential regulatory relationships rather than provide direct experimental validation. Collectively, this integrative approach may offer new insights into disease biology and help guide future experimental studies aimed at identifying biomarkers or therapeutic targets in MS.
Neurodegeneration and homelessness are deeply interconnected. Many structural, environmental, and interpersonal conditions experienced during homelessness-for example, inconsistent healthcare, forced displacement, chronic stress, and trauma-can contribute to accelerated cognitive decline through multiple pathways. Related neurocognitive impairment can also increase vulnerability to homelessness. Deficits in memory, executive functioning, attention, and impulse control can make it difficult to maintain employment, manage finances, navigate social services, and sustain supportive relationships. Together, these pathways create a reinforcing pattern: neurodegeneration can increase risk of losing housing, and homelessness can intensify the biologic and psychosocial stressors that drive neurodegeneration. Despite growing evidence suggesting a substantial burden of neurodegenerative conditions among people experiencing homelessness, these conditions are frequently underrecognized and underdiagnosed. Fragmented healthcare and symptom overlap with psychiatric conditions or substance use can hinder timely detection. Missed or delayed diagnosis has significant individual and systemic impacts. As neurodegeneration progresses without recognition or treatment, individuals may experience preventable functional decline, difficulty maintaining relationships, and repeated, often avoidable encounters with hospitals, shelters, and carceral settings. Without diagnosis, individuals may also miss opportunities to access disability benefits, supportive housing options, and personalized care planning that could significantly improve health and quality of life. Emerging models grounded in trauma-informed, harm reduction-oriented approaches-such as mobile outreach, shelter-based clinics, and Housing First programs-offer promising strategies to improve recognition of neurocognitive changes and support long-term neurologic health. Understanding and addressing the bidirectional relationship between neurodegeneration and homelessness is essential for reducing suffering, promoting stability, and delivering care that is both effective and dignity-affirming.
Certain musical abilities can endure even as language, memory, and behavior decline in dementia, yet the neural basis of this resilience remains poorly understood. We draw onbehavioral and neuroimaging evidence to explain why musicality is selectively preserved or impacted across Alzheimer's disease (AD) and the frontotemporal dementias (FTDs). Adopting a network-based perspective, we describe how musicality arises from interactions across large-scale brain systems that support perception, emotion, and memory. Evidence from case studies and neuroimaging work suggests that music engages lower-level auditory processing and higher-order networks across the brain, which may help explain the heterogeneous effects of neurodegeneration on musicality. Preserved and impaired musical abilities may reflect the selective vulnerability of distinct intrinsic connectivity networks. In early AD, relatively preserved salience and reward circuitry may sustain emotional responses to familiar music and facilitate autobiographical recall even as episodic memory declines. Degeneration of anterior temporal and salience network regions in the FTDs may disrupt the emotional and conceptual interpretation of music while leaving lower-level auditory systems relatively intact. Significant gaps remain in understanding how different components of musicality are affected in specific neurodegenerative diseases. Greater methodological standardization, larger cohorts, longitudinal study designs, and multimodal approaches will be critical for identifying how musicality is preserved or impacted across dementia syndromes. Addressing these questions may advance theoretical models of music perception in the human brain and guide the development of targeted music-based interventions that enhance emotion, memory, and quality of life for people living with dementia.
Rationale:Trachoma remains a leading cause of preventable blindness that has long persisted in Egypt. Global estimates tend to undervalue the actual national prevalence, and no previous analysis has comprehensively mapped the temporal and regional trends within the country. The present study addresses these gaps to guide elimination efforts and policy planning. Objective:To estimate the prevalence of active and chronic trachoma and associated visual impairment and blindness in Egypt through a comprehensive systematic review and meta analysis. Methods:We prospectively registered with PROSPERO (CRD420251070078) and adhered to PRISMA 2020 and Cochrane standards. Three independent reviewers searched 10 databases without language restrictions for population-based, cross-sectional surveys that reported WHO-graded trachoma outcomes. Two reviewers independently screened records, extracted data, and assessed bias using the Joanna Briggs Institute (JBI) checklist; Grading of Recommendations, Assessment, Development and Evaluations (GRADE) appraised evidence certainty. We transformed proportions using the Freeman-Tukey double arcsine transformation, pooled estimates using random-effects meta-analysis and directly age-standardized them to Egypt's 2000-2020 population structure. We performed sensitivity, subgroup, and meta-regression analyses to explore heterogeneity. Results:From 16 cross sectional surveys (n = 45 934), the pooled age standardized prevalence estimates were as follows: active trachoma in children (1-9 years) 10.8% (95% CI; 7.0-14.6), visual impairment in those cases 5.3% (95% CI; 3.2-7.5), chronic trachoma in adults (≥ 15 years) 7.2% (95% CI; 4.0-10.4), associated visual impairment 1.6% (95% CI; 1.0-2.2), and blindness 0.7% (95% CI; 0.1-1.9). Sensitivity, subgroup, and meta regression analyses demonstrated consistent estimates and no evidence of small study effects. Conclusion:Despite substantial declines, active and chronic trachoma remain well above elimination thresholds in Egypt. These findings underscore the need for sustained implementation of the SAFE strategy-particularly enhanced water, sanitation, and hygiene (WASH) infrastructure, ongoing surveillance, and targeted surgical outreach-and call for harmonized survey methods to guide and evaluate future control efforts.
This article hypothesizes the possible involvement of Lutzomyia lenti in the transmission cycle of leishmaniases. Although its vector competence has not been confirmed, this study emphasizes the need for further research on the ecology of this species, its interactions with hosts, and the environmental factors influencing its distribution and population density to assess its potential role as a Leishmania vector.
Occupational exposure remains a major driver of parasitic infections in India, largely due to caste-based discrimination that severely limits job opportunities for certain communities. Historically marginalized groups, particularly Scheduled Castes (SC) and Scheduled Tribes (ST), often have little choice but to engage in high-risk occupations such as manual scavenging, landless farming, inland and coastal fishing, tea-estate labor, informal mining, and backyard pig-rearing. Passed down through generations of exploitation, these occupations typically involve minimal or no personal protective equipment and significantly raise the risk of infections like hookworm, strongyloidiasis, visceral leishmaniasis, lymphatic filariasis, Taenia solium cysticercosis, and schistosomiasis. Because social discrimination, even in 2025, restricts these groups from accessing safer employment options, they remain trapped in a cycle of poverty and disease. Add to this their living conditions like mud houses, open defecation practices, segregation, non-secure informal jobs without proper healthcare access, and low literacy, and it is clear why these curable infections persist despite national efforts like mass drug administration and vector control. Addressing this issue effectively means directly tackling caste-driven occupational segregation. Workplace-based preventive treatment, targeted surveillance, and equity-focused policies are essential to sustainably eliminate these parasitic infections and finally close these deep-rooted health disparities that are not commonly addressed in both policy-making and literature.
Background:Sexually transmitted diseases (STDs) remain a major global public health challenge because their health consequences lead to severe complications, especially among sexually active populations. Trichomonas vaginalis (TV), Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) are three common non-viral STDs which are increasing worldwide, and co-infections are common. Methods:Designed and evaluated the performance of a multiplex polymerase chain reaction (PCR) in both dry and wet samples to detect three non-viral STDs, which were diagnosed based on syndromic case management (SCM) and uniplex PCR tests. We collected samples in duplicate (n=133), one as dry swab and the other swab was immediately put in transport medium and brought to the laboratory at ambient temperature within 4-5 hours. The total DNA was isolated from dry and wet swabs. Results:Out of 133 samples, six were positive for all three infections in both dry and wet swabs, while 127 were negative for all three. All clinical samples were then tested using uniplex PCR for each pathogen and also using triplex PCR for clinical evaluations. Conclusions:Multiplex PCR developed in-house is an effective test for simultaneous diagnosis of CT, NG, and TV and may be used for accurate and confirmed diagnosis especially in asymptomatic and suspected co-infection in low-income countries. Further evaluations of the clinical performance and the cost-effectiveness of this rapid diagnostic test on the management of multiple STI are underway.
