Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex etiology that involves environmental, genetic, and metabolic components. Among these, circadian rhythm disruption has been seen critical but underexplored component in the pathogenesis of Alzheimer’s disease. The suprachiasmatic nucleus (SCN), the central pacemaker of circadian regulation, coordinates all the physiological processes, such as sleep-wake cycles, metabolism, and neuroendocrine signalling. Tau-pathology, neuroinflammation, amyloid-β build-up, and cognitive decline in Alzheimer’s disease are all becoming gradually linked to dysregulation of the system. A detailed review of literature was performed to study the role of circadian disruption in Alzheimer’s disease. Alzheimer’s disease-related circadian rhythm dysregulation is expressed through decreased melatonin secretion, sleep disturbances, and modified SCN signalling. Neuronal dysfunction could be caused by mutations in important clock genes (BMAL1, PER, CRY, and CLOCK). Sleep deprivation increases the buildup of amyloid-β and impairs glymphatic clearance. Also, tau pathology interrupts the circadian clock, further speeding up cognitive decline. Chronotherapies involving melatonin supplementation, light therapy, environment, and sleep hygiene provide promising effects in restoring circadian regulation and enhancing cognitive performance. According to the research from both experimental and clinical studies, there is a link between circadian rhythm abnormalities and Alzheimer’s disease. Non-invasive biomarkers for the early identification of circadian nonalignment may aid in preventative measures. Researchers are currently looking into new treatment options that could slow down the progression of Alzheimer's disease. The integration of circadianbased therapies into individualised therapy paradigms for Alzheimer's disease patients should be the main focus of future research.
INTRODUCTION:The current study was carried out to assess the pharmacological action of combine effect of Poloxamer 188, Lycopene, and Quercetin on memory and energy deficit in Huntington's disease-like signs induced by 3 Nitropropionic acid in Wistar rats. METHODS:After one week of acclimatization all animals were randomly assigned in six groups, (n = 6), as normal control, Huntington's disease control, Lycopene treated (25 mg/kg po), Quercetin treated (50 mg/kg po), combinations with and without Poloxamer 188 (80 mg/kg po) with adjunct administration of 3 nitropropionic acid (10 mg/kg i.p.) except in normal control. Memory and energy deficits were induced by i.p. administration of 3 Nitropropionic acid (10 mg/kg) for 14 days. A novel object recognition test was assessed on the 14th and 15th days of the experiment, post-treatment, and other biochemical parameters were examined at the end of the experiment. RESULT:The results showed that the 3-nitropropionic acid administration for 14 days produced memory and energy deficits in rats. Moreover, the combination of Lycopene and Quercetin, with and without Poloxamer 188, showed significant effects on memory enhancement, energy deficit, and body weight compared to single-drug therapy. However, the combination did not produce a significant increase in brain weight compared to single-drug therapy. Moreover, the combination also showed remarkable enhancement in Succinate dehydrogenase activity and reduction in Lactate dehydrogenase activity compared to monotherapy. DISCUSSION:The combined therapy of lycopene, quercetin, and poloxamer 188 significantly improved 3-nitropropionic acid-induced cognitive deficits by reducing oxidative stress and enhancing cholinergic function. This synergistic effect also normalized key mitochondrial enzymes, suggesting strong neuroprotective potential against Huntington's disease progression. CONCLUSION:Administration of 3-nitropropionic acid for 14 days produces memory and energy deficits in rats. Combining the effects of Lycopene and Quercetin, with or without Poloxamer 188, enhances memory and reduces energy deficit more effectively than mono-therapy. This study assessed the effects of combined lycopene, quercetin, and poloxamer 188 treatment on cognition and energy deficits in a 3-nitropropionic acid-induced rat model. Treating with a combination of the three compounds resulted in behavioral and biochemical improvements compared to the disease control group. There may be a tendency for the combined treatments to have additive effects on the subjects compared to individual treatments. However, the results of this study should be interpreted with caution.
Cortisol, regulated by the hypothalamic-pituitary-adrenal (HPA) axis, is critical for stress response, metabolism, and immune function. Its dysregulation is increasingly implicated in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). This review synthesizes evidence on cortisol's role in neurodegenerative disorders, exploring its mechanisms, clinical implications, and therapeutic potential. This study analyzed preclinical models, clinical studies, and biomarker data to elucidate cortisol's impact on neurodegeneration. Key mechanisms include glucocorticoid and mineralocorticoid receptor-mediated effects on synaptic plasticity, neuroinflammation, and oxidative stress. In AD, elevated cortisol accelerates cognitive decline, hippocampal atrophy, and amyloid-β accumulation. In PD, higher cortisol levels correlate with gait dysfunction and dopaminergic neuron loss. HD shows variable cortisol profiles, with early hypocortisolism shifting to hypercortisolism in later stages, linked to depression. In ALS, elevated cortisol hastens disease progression and neuroinflammation. In MS, HPA axis hyperactivity is associated with cognitive deficits and lesion activity, though it may support remyelination. Chronic stress exacerbates these effects across disorders, promoting neuronal vulnerability. Cortisol dysregulation is a significant contributor to neurodegenerative pathology, acting as both a biomarker and therapeutic target. Emerging interventions, including glucocorticoid receptor antagonists, cortisol synthesis inhibitors, and stress reduction strategies, show promise in mitigating neuronal damage. Personalized, stage-specific therapies and longitudinal studies are needed to optimize cortisol-targeted treatments for neurodegenerative diseases.
Neuroscience is making tremendous progress toward precision medicine, with nanotechnology playing a critical role in overcoming hurdles to successful brain medication delivery. Nano magnetism, namely biohybrid magnetoelectric nanocarriers (MENs), has emerged as a potential method for targeted and non-invasive medication delivery in neurological illnesses. These nanocarriers possess magnetoelectric properties, enabling stimulus-responsive drug release that is externally controlled. This allows for precise targeting across the blood-brain barrier (BBB), with exceptional spatial and temporal resolution. MENs can deliver neurotherapeutics deep into brain regions by combining magnetic guidance with electrical stimulation, thereby improving treatment outcomes for conditions such as Alzheimer's, Parkinson's, epilepsy, and glioblastoma. Furthermore, their biohybrid nature, which is accomplished by functionalizing nanocarriers with biocompatible coatings, peptides, or membranes produced from neural cells, increases biostability, decreases immune response, and improves neuron targeting. This review investigates the underlying concepts of magnetoelectric nanocarriers, production processes, and interactions with brain tissue. It dives deeper into recent advances in precision neural drug delivery, including the effect of external magnetic and electric fields on regulated drug release, neurostimulation, and neuromodulation. While MENs have tremendous promise, long-term biocompatibility, precise control systems, and regulatory restrictions continue to impede clinical translation. Future research should concentrate on enhancing nanocarrier design, increasing targeting efficiency, and undertaking large-scale preclinical and clinical trials. Magnetoelectric nanocarriers have the potential to transform non-invasive neurotherapeutics by bridging the gap between nano magnetism and neuroscience, resulting in safer and more successful treatment paradigms for complex brain illnesses.
Alzheimer's Disease (AD) is a neurodegenerative disorder that characterizes depletion of memory, cognition, and a change in behavioural patterns. There is no standard treatment that completely cures this prevalent disease. This review delves into the existing pathologies of AD, which include the Aβ plaques accumulation, neurofibrillary tangles and Lewy bodies formation, and the influence of the P2X7 receptor on cellular mechanisms of neuronal cells like microglial cells, astrocytes and oligodendrocytes and also its influence on pathways such as JAK2/STAT3, NGF signalling, (Transactive response DNA binding protein) TDP-43 Proteinopathy, Wnt/β-Catenin signalling, and FGF7/FGFR2/PI3K/Akt causing AD. It discusses the unifying role of the P2X7 receptor mediating these pathways that link to the occurrence and progression of AD. The role of the Purinergic receptor (P2X7 receptor), a ligand-gated ion channel activated by extracellular ATP, was examined across existing cellular mechanisms and possible pathways involved in AD, as well as the co-pathologies encompassed and their hypothetical relationship with the P2X7 receptor. Additionally, the current P2X7 receptor antagonists treating neurotoxicity are discussed along with existing pre-clinical and clinical data. This may further advance drug development by targeting the P2X7 receptor to mitigate AD across multiple mechanisms.
The WNT signaling pathway plays a significant role in various biological processes during embryonic development, childhood, and adulthood. It is involved in neurogenesis, synapse formation, and such cognitive processes as learning and memory in the CNS. Dysregulated WNT signaling is associated with cognitive decline, synaptic dysfunction, neuronal loss, and has been associated with diseases like leukemia and colorectal cancer. The studies show that WNT/β-catenin signaling affects the cellular, molecular, and metabolic mechanisms that promote disease progression. The WNT pathway is a potential therapeutic target because it helps maintain neuronal survival, supports the growth of new nerve cells, and enhances synaptic plasticity. WNT signaling is important for stem cell selfrenewal and differentiation. Research is being conducted on therapeutic methods targeting WNT signaling to treat neurological diseases and cancer. This review explores the connection between WNT signaling and the pathology of Alzheimer's disease. This review explores the role of WNT signaling in AD pathogenesis, with a focus on the Wnt/β-catenin pathway as a therapeutic target. It summarizes existing findings to demonstrate that WNT signaling is a context-dependent regulatory network in which a shift from protective canonical activity to dysregulated non-canonical and inflammatory pathways contributes to disease progression.
Abstract: The WNT signaling pathway plays a significant role in various biological processes during embryonic development, childhood, and adulthood. It is involved in neurogenesis, synapse formation, and such cognitive processes as learning and memory in the CNS. Dysregulated WNT signaling is associated with cognitive decline, synaptic dysfunction, neuronal loss, and has been associated with diseases like leukemia and colorectal cancer. The studies show that WNT/β-catenin signaling affects the cellular, molecular, and metabolic mechanisms that promote disease progression. The WNT pathway is a potential therapeutic target because it helps maintain neuronal survival, supports the growth of new nerve cells, and enhances synaptic plasticity. WNT signaling is important for stem cell selfrenewal and differentiation. Research is being conducted on therapeutic methods targeting WNT signaling to treat neurological diseases and cancer. This review explores the connection between WNT signaling and the pathology of Alzheimer's disease. This review explores the role of WNT signaling in AD pathogenesis, with a focus on the Wnt/β-catenin pathway as a therapeutic target. It summarizes existing findings to demonstrate that WNT signaling is a context-dependent regulatory network in which a shift from protective canonical activity to dysregulated non-canonical and inflammatory pathways contributes to disease progression.
Abstract: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by social communication deficits, restricted interests, and repetitive behaviors. Its etiology involves genetic and environmental factors. This review examines the role of neuronal autoantibodies in ASD development. Autoantibodies mistakenly attack the body's tissues, including critical components of the nervous system, disrupting brain function. Examples include autoantibodies against NMDA and AMPA receptors, as well as myelin oligodendrocyte glycoprotein (MOG), which interfere with neurotransmitter signaling, synaptic function, and the integrity of the blood- -brain barrier, contributing to ASD symptoms. Maternal autoantibodies (MAAs) targeting fetal brain proteins can pass the placental barrier and disturb fetal brain development, potentially leading to ASD. Understanding autoantibodies in ASD pathogenesis offers insights into therapeutic targets and diagnostic markers for this disorder.
The establishment of new synaptic connections driven by synaptic plasticity at excitatory synapses is a prerequisite for learning and memory in the brain. Growing evidence suggests that disruption in synaptic plasticity mechanisms contributes to various forms of dementia. The GSK3β signaling system significantly influences dementia. Amyloid beta (Aβ) can activate GSK3β, so establishing a destructive feedback loop that can further exacerbate the condition of dementia. Potassium ion channels (KCNQ/Kv7), particularly Kv7.2 and Kv7.4, regulate neuronal excitability and synaptic plasticity, mitochondrial Ca2+ overload and mitophagy. KCNQ/Kv7.2 channel dysfunction contributes to hyperexcitability and synaptic dysfunction, exacerbating dementia. Hyperactive GSK3β phosphorylates Kv7.2 channels, leading to KCNQ channel inactivation. Research indicates that combining GSK3β inhibitors with KCNQ/Kv7 channel activators yields a synergistic effect, enhancing neuroprotection and stabilizing neuronal excitability, thus providing a multi-faceted approach in dementia management. Challenges remain in fully elucidating the mechanisms underlying the GSK3β and KCNQ/Kv7 interactions, alongside issues regarding their specificity and safety. This review examines the crosstalk between GSK3β and KCNQ/Kv7 channels and the management of dementia with synergistic combination of GSK3β inhibitors and KCNQ/Kv7 channel activators.
Abstract: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition characterized by persistent difficulties in social interaction, communication, and the presence of repetitive behaviors or restricted interests. Its causes are complex, involving both genetic predisposition and environmental factors that affect early brain development. Recent research has focused on uncovering the biological mechanisms contributing to ASD. In this review, we summarize current findings, emphasizing pathways such as altered GABAergic signaling, oxidative stress, calcium imbalance, and disruptions in mTOR and Wnt signaling. The gut–brain axis, an emerging area of study, is also explored for its potential influence on neurodevelopment and behavior. These interconnected systems help explain how molecular and cellular dysfunctions may result in the behavioral and cognitive features observed in ASD. Diagnostic practices based on DSM-5 criteria are reviewed, including the updated classification of symptom severity. Treatment options are discussed, covering well-established behavioral therapies like Applied Behavior Analysis (ABA) and Cognitive Behavioral Therapy (CBT), along with pharmacological approaches to manage associated symptoms. Despite advancements, current therapies often fall short of meeting the diverse needs of individuals with ASD. Increasing emphasis is being placed on multidisciplinary, personalized care models that integrate medical, psychological, and educational support. By drawing insights from neuroscience, genetics, psychology, and clinical research, this review aims to guide future efforts in improving early diagnosis and developing more targeted, effective interventions to enhance the quality of life for individuals with ASD and their families.
Neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases present complex pathophysiology and lack effective therapies, confronting growing global health challenges. Over the past few decades, nanomaterials have undergone an astonishing revolution in the research and scientific communities due to their remarkable properties and notable applications in energy, environment, agriculture, health, and the pharmaceutical sectors. Nanomaterials are currently gaining recognition for their significant consequences due to their several uses in health and wellbeing. A promising tool for the investigation and management of these conditions is fluorescent carbon dots (CDs), a family of nanomaterials with remarkable properties, including biocompatibility and versatility. This review explores the multifaceted applications of fluorescent carbon dots for various Neurodegenerative and miscellaneous neurodegenerative disorders. This includes types of CDs, precursors, methods of synthesis, quantum yield, and their specific uses. The exceptional properties of CDs make them useful tools for bioimaging, enabling the study of brain structure and tracking the course of disease. CDs offer potential as drug delivery vehicles and theranostic agents capable of crossing the BBB and targeting specific neuronal populations. This study aims to shed light on fluorescent CDs in the field of NDs, outlining creative approaches for the diagnosis, treatment, and monitoring of neurological disorders.
Abstract: The Hypothalamic–Pituitary–Adrenal (HPA) axis dysfunction hypothesis of depression posits that maladaptive stress responsivity, sustained hypercortisolemia, and impaired Glucocorticoid Receptor (GR) signaling constitute core neurobiological mechanisms underlying depressive pathology. Dysregulation of this system, characterized by impaired glucocorticoid receptor feedback, sustained hypercortisolemia, and altered diurnal cortisol rhythms, contributes to neuronal vulnerability, maladaptive stress responsivity, and the progression of depressive pathology. This review synthesizes clinical and preclinical evidence linking HPA axis dysfunction to depression, with particular focus on key molecular targets including corticotropin-releasing hormone (CRH) receptors, glucocorticoid and mineralocorticoid receptors, and the arginine vasopressin system. In addition, we examine the emerging role of oxidative stress and inflammatory mediators in amplifying HPA dysregulation, and discuss the potential utility of biomarkers such as cortisol, ACTH, F2- isoprostanes, and 8-OHdG as diagnostic and treatment-responsive indicators. While current data provide compelling support for the HPA axis dysfunction hypothesis, methodological variability, reliance on peripheral measures, and limited longitudinal studies constrain causal inference. Future research should prioritize standardized biomarker panels, integration of multi-omics approaches, and validation of predictive signatures to enable precision medicine. Importantly, the review highlights novel therapeutic strategies, including CRH receptor antagonists, glucocorticoid receptor modulators, mineralocorticoid receptor agonists, and agents targeting oxidative and inflammatory pathways, as promising candidates for next-generation antidepressant development. By consolidating mechanistic, clinical, and translational evidence, this review highlights oxidative stress–HPA axis interactions as a pivotal determinant of depression vulnerability, underscores critical limitations in the current evidence base, and identifies future research priorities aimed at advancing biomarker-guided strategies for the prevention and treatment of depression.
Abstract: Exosomes represent a promising class of naturally produced nanoparticles that exist at the nanoscale and carry a negative surface charge under physiological conditions. These tiny membranebound vesicles are released by cells throughout the body and function as biological messengers, transporting various molecular cargos between cells and facilitating critical cell-to-cell communication pathways. Existing therapies for neurodegenerative disorders face two critical barriers: they cannot precisely target the affected brain areas, and the blood-brain barrier blocks most potential treatments from entering the brain. Exosomes offer a promising solution to these challenges. Unlike most synthetic drug delivery systems that struggle to penetrate the brain's protective barrier, these naturally derived nanocarriers exhibit an inherent capacity to traverse the blood–brain barrier. This unique property, combined with their capacity for efficient intracellular delivery of therapeutic payloads, positions exosomes as an exciting platform for transporting pharmaceutical agents to the affected neural tissues. Through strategic engineering and modification, these vesicles can be transformed into highly precise delivery vehicles capable of targeting specific organs, tissues, or even individual cell types. This review explores the therapeutic potential and drug delivery applications of exosomes in the management of major neurodegenerative disorders. This review provides an in-depth examination of exosome biogenesis, current isolation methodologies, and surface engineering strategies, while critically evaluating the strengths and limitations of each approach. In addition, this review summarizes the current preclinical models and provides an overview of ongoing clinical trials investigating exosome-based therapies for neurological disorders.
INTRODUCTION:Zolpidem is a widely used non-benzodiazepine hypnotic that is used as a treatment for insomnia due to its rapid onset and perceived safety. Nevertheless, rising clinical reports and post-marketing surveillance have identified serious neuropsychiatric adverse effects, such as hallucinations, perceptual disturbances, and complex sleep-related behaviors, such as sleep-driving and sleep-eating, as being frequent and often unnoticed by the patient. The consequences of such events can be severe personal injury and litigation. Regardless of these issues, there are few comparative data between zolpidem and newer hypnotics. METHODS:A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science for studies published between 2020 and 2025. RESULTS:Zolpidem was commonly linked to complex sleep acts, amnesia, and hallucinations, especially when in high dosage and when the patients had psychiatric comorbidities. On the contrary, some more recent ones, like orexin receptor antagonists, were less subject to such adverse effects, whereas the melatonin-based therapies were associated with positive safety profiles but lesser hypnotic efficacy. A number of case reports reported criminal charges in relation to zolpidem-induced altered states of consciousness. CONCLUSION:Zolpidem, despite its usefulness in the management of insomnia, has a relatively high likelihood of neuropsychiatric adverse effects, particularly among women, the elderly, psychiatric patients, and those who have undergone polypharmacy. Environmental risk-benefit evaluation must be performed cautiously and individually, prescribing zolpidem while taking into account patientspecific clinical and pharmacokinetic parameters.
INTRODUCTION:Treatment with Botulinum Toxin (BT) is safe and effective. Nonetheless, dysphagia is perhaps the most common side effect of BT injections for Cervical Dystonia (CD). We aimed to characterize the population at risk of suffering from dysphagia following BT injections of cervical muscles. METHODS:This is a retrospective observational study. We retrieved demographic and clinical data from the files of all patients diagnosed with CD who attended the Movement Disorders Unit at Shaare Zedek Medical Center during the years 2019 to 2025, and who were regularly treated with BT. The Sternocleidomastoids (SCMs) were injected either under Ultrasound Guidance (USg) or unguided, according to Anatomic Landmarks (AL). Thirty patients (18 females, 243 treatments) were included. RESULTS:Dysphagia was reported in 12.6% of treatments, with a higher incidence in females compared to males (16.9% vs. 5.3%, p = 0.02). All reports of dysphagia (n = 25) were mild. Unguided SCM injections caused significantly less dysphagia than USg SCM injections (7.6% and 18.1%, respectively, p = 0.02). Among elderly patients (≥ 60 years), the incidence of dysphagia was also lower with unguided injections compared to US-guided injections (6.5% vs. 31.3%, p = 0.03). DISCUSSION:Unguided BT injections into the Sternocleidomastoid (SCM) muscle resulted in a lower incidence of dysphagia compared to Ultrasound-guided (USg) injections. Additionally, elderly patients and women are at a heightened risk of experiencing dysphagia. CONCLUSION:Dysphagia appears to be a common side effect of US-guided BT injections, and it is possibly related to SCM injections. Caution should be particularly made in older females. We recommend treating the SCM muscles without guidance, particularly in older female patients.
Syntaxin-4 (Stx4), a member of the Qa-SNARE protein family, is a pivotal regulator of membrane trafficking. Stx4 is predominantly localized at the postsynaptic membrane of neurons and in glial cells, where it is essential for synaptic plasticity and the maintenance of neuronal homeostasis. Stx4 facilitates the activity-dependent exocytosis of glutamatergic receptors, thereby governing the balance between Long-Term Potentiation (LTP) and Long-Term Depression (LTD). Emerging evidence suggests that dysregulation of Stx4 is intricately linked to the pathogenesis of neurodegenerative diseases. In Alzheimer's disease, Stx4 is involved in synaptic dysfunction and cognitive impairment through its interactions with amyloid-β (Aβ) and tau pathologies, affecting receptor recruitment at dendritic spines. In Parkinson's Disease (PD), Stx4 contributes to α-synuclein proteostasis, dopaminergic signaling, neuroinflammation, and the maintenance of blood-brain barrier integrity. While its presence in cerebrospinal fluid highlights its potential as a candidate biomarker for these diseases, further validation is required to establish clinical utility. This review summarizes current mechanistic insights into Stx4's multifaceted roles in the neurodegenerative disorders and explores the therapeutic prospects of targeting Stx4-mediated pathways due to its translational potential.
Depression is a globally prevalent mental disorder characterized by persistent low mood and cognitive deficits, with high incidence and recurrence rates, causing a heavy burden on individual health and public health systems worldwide. MicroRNAs (miRNAs), a class of single-stranded noncoding RNAs (ncRNAs) composed of 18-25 nucleotides, regulate gene expression at the posttranscriptional level by binding to the 3' UTR of target mRNAs. Due to their ability to inhibit translation and their high enrichment in brain tissue, miRNAs have become key players in depression research, with increasing evidence supporting their potential as diagnostic biomarkers and therapeutic targets for the disease. Among these miRNAs, miR-206 is considered a critical regulator of stress susceptibility and is highly expressed in brain regions associated with depression, including the hippocampus and prefrontal cortex (PFC). Numerous preclinical studies have confirmed the role of miR- 206 in stress responses. However, the precise neurobiological mechanisms involved in depression, including its regulation of neurogenesis, neuroinflammation, the gut-brain axis, and interactions with key molecules such as BDNF, remain incompletely understood. This review synthesizes the latest research progress on miR-206, focusing on its multifaceted involvement in the pathophysiology of depression. By summarizing findings on its downstream signaling pathways, tissue-specific expression patterns, and regulatory effects on antidepressant effects such as ketamine-mediated regulation, this study aims to provide new insights into the diagnosis and treatment of major depressive disorder (MDD) and offer important guidance for the development of next-generation antidepressant drugs.
Introduction to evaluate the acute effects of continuous moderate-intensity aerobic exercise and high-intensity interval training (HIIT) on heart rate variability (HRV) and psychoaffective responses in patients with bipolar disorder (BD) and healthy controls.Methods Eight BD patients and eight controls underwent baseline assessments, including anthropometric measurements and a submaximal exercise test to determine VO2Max, followed by two randomized exercise sessions. In one session, participants performed 12 min of continuous exercise at 65%VO2Max, and in the other, during the HIIT protocol, participants engaged in six 45-s bouts at 100%VO2Max, each followed by a 1-min and 15-s recovery period at 40%VO2Max. Pre- and post-exercise measurements included psychoaffective scales (feeling scale - FS, felt arousal scale - FAS, and SUDs anxiety scale) and HRV assessments recorded during a 10-minute rest period under controlled conditions.Results Regarding RMSSD, both participants and sessions demonstrated a significant increase in this indicator (p=0.012). The BD significantly increased VLF and LF values and reduced HF values for both exercise sessions. Meanwhile, the LF/HF ratio showed a significant increase only in the HIIT session. For the control group, only a significant reduction in the HF index in both sessions and an increase in the LF/HF ratio only in the HIIT session. The FAS showed significant increases in bodily activation post-exercise across groups and modalities, while the FS demonstrated significant positive shifts in affective valence, with larger improvements following HIIT. Both exercise protocols produced significant reductions in anxiety levels (p=0.001), with HIIT showing a trend toward superior anxiolytic effects in BD patients.Discussion The improvement in vagal tone and HRV modulates the function of critical brain regions involved in emotional regulation, such as the prefrontal cortex, amygdala, and anterior cingulate cortex. This modulation reduces limbic hyperactivity and impulsivity while influencing monoaminergic pathways, attenuating excessive dopaminergic signaling, thereby contributing to enhanced mood stability and the reduction of affective disturbances in individuals with BD.Conclusion Both continuous moderate-intensity exercise and HIIT elicited favorable acute autonomic and psychoaffective responses in BD patients and healthy controls. Notably, HIIT tended to produce greater affective and anxiolytic benefits in individuals with BD.
Introduction: GABAergic deficits are involved in depressive disorders; the roles of hippocampal GABA(A) receptors in the pathogenesis and pharmacotherapy of depression have not been fully studied. The hippocampal alpha 6 GABA(A) receptors (alpha(6), Gabra6) have a critical role in the pathophysiology of major depressive disorder. The present study determined the roles of alpha(6) subunits in the pathogenesis and antidepressant treatment of depression in a rat model of major depression induced by Chronic Repeated Restraint (CRR). Materials and Methods: Male Sprague-Dawley rats were restrained daily in an air-accessible Plexiglas cylindrical restrainer. The tricyclic antidepressant clomipramine was provided to rats daily by drinking (50 mg/kg) after restraint stress. The novelty suppressed feeding tests, open field tests, and sucrose preference tests were performed to evaluate depressive behaviors in rats. QPCR was performed to measure Gabra6 mRNA levels in rat hippocampus, and immunohistochemistry was performed to detect alpha(6) protein localization in the hippocampus. The patch-clamp technique was used to test the electrophysiological characteristics of evoked inhibitory postsynaptic currents (eIPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs) in hippocampal CA1 pyramidal neurons. Results: We observed that CRR stress decreased sucrose preference, travel distance, and center time in the open field test, and increased latency to feed in the novelty-suppressed feeding test. alpha(6) subunits were mainly expressed on interneurons in CA1 of the hippocampus. CRR stress down-regulated alpha(6) subunits of the GABA(A) receptor in the hippocampus. Patch-clamp studies revealed that CRR stress decreased the amplitude of eIPSCs while increasing the frequencies and amplitudes of sIPSCs in CA1 pyramidal neurons, indicating that inhibitory synaptic transmission in the hippocampus was altered by CRR stress. Chronic administration of clomipramine ameliorated depressive behaviors, restored the normal expression of hippocampal alpha(6) subunits, and decreased sIPSC frequencies of pyramidal neurons in rats subjected to CRR stress. Discussion: These results suggest that clomipramine-induced upregulation of alpha(6) subunits attenuated abnormal inhibitory synaptic transmission in the hippocampus, which might contribute to its antidepressant actions in relieving depressive behaviors induced by CRR stress. Conclusions: The roles of alpha(6) subunits in the pathogenesis and antidepressant treatment of depression may provide novel therapeutic avenues for the development of antidepressants.
INTRODUCTION:Sufficient amounts of nutrients have been considered important in the pathophysiology of obsessive-compulsive disorder (OCD). In recent years, many studies have examined alleviating symptoms of neurological and behavioral disorders through nutritional change. Thus, we aim to synthesize current knowledge on serum levels of nutrients and other nutraceuticals and their potential impact on OCD symptoms. METHODS:We conducted a targeted literature search of PubMed, EMBASE, and Scopus, including clinical investigations and relevant animal research in June 2025, without applying any publication date restrictions. Articles were selected based on their focus on nutrient interventions and reported OCD-related outcomes. RESULTS:We reviewed evidence on nutritional and neurochemical factors in OCD, including vitamins (B₆, B₉, B₁₂, C, D, and E), mineral supplements (zinc, magnesium, selenium, iron, calcium), glycine, homocysteine, glutamate, N-acetylcysteine, D-cycloserine, omega-3, and inositol, alongside selected pharmacologic neuromodulators including gabapentin, serotonin-targeting agents. DISCUSSION:Notable and relatively consistent differences in homocysteine, glutamate, vitamin B₁₂, and vitamin E, as well as zinc levels, were observed between individuals with OCD and healthy controls, suggesting their potential as biomarkers and therapeutic targets. Preliminary evidence also indicates that supplementation with vitamin C, B₆, B₉, B₁₂, vitamin E, zinc, and N-acetylcysteine may contribute to symptom improvement in OCD. CONCLUSION:Certain nutritional interventions appear to offer safe, well-tolerated adjunctive benefits in OCD treatment, likely through anti-inflammatory and antioxidant pathways. However, because of heterogeneity in study designs, small sample sizes, and variable dosing regimens, further research should determine optimal supplement types, dosages, and treatment durations.
