Search Results (183)

Although clomipramine (CLO) is widely used as a serotonin reuptake inhibitor, its subchronic administration during the early stages of brain development leads to depressive-like behaviors in adulthood. High doses of CLO have been linked to mitochondrial impairment and increased reactive oxygen species in cells and adult animals. It is unknown whether subchronic administration of this drug at early ages can induce oxidative stress (OS) in adulthood. The objective of this study was to evaluate OS and cellular damage in the prefrontal cortex and limbic system (hippocampus and amygdala) of rats exposed to CLO neonatally. Methods: Forty male Wistar rats were divided into experimental (EXP) and control (CTRL) groups. The EXP animals received CLO (15 mg/kg, twice daily, subcutaneously, postnatal days 5–35); the CTRL animals received saline. At 55 and 85 days of age, the brains were collected for biochemical assays and histological analysis. Results: Rats exposed to neonatal CLO presented significant reductions in reduced glutathione (GSH) and increases in oxidized glutathione (GSSG) and malondialdehyde in both studied regions, especially on day 85. The GSH/GSSG ratio decreased, indicating persistent OS. Histology revealed neuronal degeneration, pyknotic nuclei, cell shrinkage, and disorganized tissue, which progressed from days 55 to 85. Conclusions: Early exposure to CLO can cause long-lasting neurochemical and structural alterations in the brain regions associated with the regulation of emotions and some behavioral responses that can persist over time and affect behavior in adulthood. Full article

This commentary explores the parallel neuroanatomical and neurobiological evolution that ultimately led to modern dogs and humans, through domestication and self-domestication, respectively. The selective pressures for benignness and enhanced prosociality have reshaped brain anatomy and cognitive architecture in both Canis familiaris and Homo sapiens, leading to analogous changes including a reduction in limbic system volume and expansion of the prefrontal cortex, critical for executive control and social cognition. From a molecular point of view, shared genetic and epigenetic underpinnings of these adaptations and their implications gave rise to parallel trajectories in brain aging; notably, the emergence of canine cognitive dysfunction. Interestingly, this canine age-related cognitive decline presents significant overlaps with Alzheimer’s disease in terms of both behavioral presentation and underlying pathology. In the context of a One Health perspective, the profound influence of shared environmental exposures, such as urbanization, pollutants, and stressors, on neurodevelopment, cognitive aging, and disease susceptibility offers a compelling translational model for understanding brain health within intertwined ecological and social contexts. Full article

Background/Objectives: Autoimmune encephalitis (AIE) comprises a heterogeneous group of inflammatory central nervous system (CNS) disorders characterized by variable clinical presentations and antibody profiles. This study aimed to identify poor prognostic factors in AIE by retrospectively evaluating patients diagnosed based on clinical, radiological, and serological findings. Methods: Forty-four patients diagnosed with AIE between 2014 and 2024 were included. Demographic, clinical, radiological, and serological data were collected retrospectively. Patients were grouped based on antibody localization (intracellular, surface, and seronegative) and classified by treatment response. Poor prognosis was defined as a lack of objective clinical improvement to treatment or death. Results: The mean age was 57.8 ± 13.6 years, with a female-to-male ratio of approximately 1:1. Limbic encephalitis (LE) was the most common clinical presentation (43.2%). Malignancy was detected in 33.3% of patients, most frequently in those with SOX1 (83.3%), anti-Hu (60.0%), and anti-Yo (50.0%) antibodies. Anti-SOX1 positivity was significantly associated with both malignancy (OR = 27.5, p = 0.007) and mortality (OR = 13.2, p = 0.009), while anti-LGI1 positivity correlated with the absence of malignancy (p = 0.036). Patients with LE showed significantly better treatment responses (OR = 14.0, p = 0.019). Mortality was 20.1% overall and highest among anti-SOX1-positive patients (66.7%). The presence of multiple antibodies was associated with higher mortality and poorer prognosis, although not statistically significantly. Conclusions: Anti-SOX1 positivity is a key indicator of poor prognosis in AIE and is strongly associated with both malignancy and mortality. In contrast, LE presentation was linked to a better treatment response. Antibody profile, clinical features, and malignancy screening are critical for risk stratification and guiding management in AIE. Full article

Melanocortin receptors (MCRs) are responsible for various functions ranging from skin pigmentation, regulation of appetite, stress response and cognition, steroid synthesis, and energy balance to cellular regeneration and immunomodulation. The genetic polymorphism with tissue distribution ranging from the brain, limbic system, and adrenal cortex to neutrophils, monocytes, and macrophages is evident in MCRs. The mutations in MC1R, MC2R, MC3R, and MC4R genes are associated with risk of melanoma, familial glucocorticoid deficiency, obesity, and type 2 diabetes mellitus, respectively. Meanwhile, MC1R, MC2R, and MC5R genes are involved in the risk of major depressive disorder. Melanocortin receptors are involved in different inflammatory disorders, i.e., atopic dermatitis, autoimmune uveitis, sarcoidosis, respiratory diseases, multiple sclerosis, scleroderma, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer’s disease, arthritis, and reperfusion injury. Several newer therapeutic agents related to MCRs have numerous advantages over the current anti-inflammatory drugs, demonstrating therapeutic relevance. Among them, α-MSH analogs play a role in atopic dermatitis and scleroderma, and MC1R agonist Dersimelagon has shown effectiveness in systemic sclerosis. The FDA has recently approved the repository corticotropin injection (RCI) to treat sarcoidosis. The FDA has also approved various melanocortin agonists, i.e., Bremelanotide, Afamelanotide, and Setmelanotide, for the treatment of hypoactive sexual desire disorder, Erythropoietic protoporphyria, and obesity, due to pro-opiomelanocortin and leptin receptor deficiency, respectively. Therefore, this review aims to summarize the function and genetic polymorphism of melanocortin receptors, regulatory pathways involving MCRs, and the existing evidence of the prime effect of MCRs on inflammatory responses via different mechanisms and their potential therapeutic use in inflammatory diseases. Full article

In Alzheimer’s disease, accumulation of Aβ and tau aggregates in the limbic and cortical regions of the brain forms the pathological basis for the onset of memory loss and cognitive abnormalities. The neuronal desecration inflicted by these toxic pile-ups will rouse the onset of innate immune defense mechanisms including astrogliosis within the neuronal milieu. A potential ramification of astrogliosis is the overproduction and spillage of GFAP into the brain circulation. Execution of GFAP vital physiological functions rests upon the preservation of its filamentous structure as well as its cytoskeletal interactions. Any anomaly that hampers the structural integrity of GFAP will engender filament disassembly, cytoplasmic aggregation, and decreased solubility with the resultant deleterious consequences. The potency of GFAP as a reliable biomarker in the blood also rests on its ability to navigate the glymphatic excretory pathways and spill into the systemic circulation. Recent reports have suggested GFAP is a dependable marker for auguring subtle disease changes in traumatic brain injury (TBI) and AD. However, pathological anomalies such abnormal structural integrity, cleavage, impaired drainage pathways, and alternative isoforms will lessen its potency and thwarts its ability from becoming a full-fledged and stable biomarker for neurological diseases. Understanding the GFAP biology, including factors that influence its structural integrity and excretory pathways, will be crucial and this review underscores these sections in a succinct manner. Thorough comprehension of GFAP biology is the principal step in unearthing its potential as a powerful marker for auguring disease initiation, and progression in TBI and AD. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder primarily characterized by memory loss and cognitive decline, which significantly impacts patients’ quality of life and imposes substantial emotional, practical, and economic burdens on their families. As the most common cause of senile dementia, AD currently affects approximately 50 million people worldwide, with projections indicating a threefold increase by 2050 due to rising life expectancy and an aging global population. Diagnosis of AD remains challenging. Neuroimaging techniques reveal atrophy in critical brain regions, particularly in the cortex, hippocampus, and limbic system, which are essential substrates for memory, personality changes, and other cognitive functions. The hallmark molecular changes associated with AD include the accumulation of β-amyloid plaques and the formation of tau protein tangles. Several underlying mechanisms contribute to neuron loss, such as oxidative stress, neuroinflammation, microbial dysbiosis, and insulin resistance. In this context, exosomes—small extracellular vesicles that facilitate cell communication—transport proteins, DNA, mRNA, and non-coding RNA (ncRNA), all of which play a significant role in the neurobiology of AD. Furthermore, emerging research indicates that exosomal ncRNAs may serve as promising biomarkers for AD, offering the possibility of improved diagnostic precision. This review explores the potential of exosomal ncRNAs—specifically circular RNAs and microRNAS—as non-invasive biomarkers for AD, highlighting recent advances and future directions in translational studies. Full article

The bed nucleus of the stria terminalis (BNST) is a heterogeneous and complex limbic forebrain structure, which plays an important role in drug addiction and anxiety. Dynorphin and kappa-opioid receptors (DYN/KOR) comprise a crucial neural system involved in modulating stress-induced drug and alcohol addiction. Previous studies have highlighted the BNST as a brain region with a strong DYN/KOR expression. However, no research has been conducted on the adolescent plasticity of this system. In the present study, we used 20- and 60-day-old Wistar rats to reveal the adolescent dynamics and possible sex differences of the DYN/KOR system in certain BNST nuclei associated with addiction behavior. We found a low expression of DYN in neuronal perikarya and a significant increase in DYN-containing nerve fibers in the lateral posterior and lateral dorsal nuclei of the rat BNST. In addition, an enhanced expression of KORs was observed in the examined BNST subnuclei with some sex differences favoring females, thus highlighting the importance of considering critical developmental differences between sexes in research. The dynamics of the DYN/KOR system observed in this study may help to explain the increased vulnerability of adolescents for developing drug and alcohol addiction. Full article

The mammalian amygdala is located in the temporal lobe of the telencephalon and plays a key role in limbic processing. Recently, our group proposed a radial morphological model to understand the glutamatergic (pallial) part of this nuclear complex in terms of separate progenitor domains. This model explains the amygdala region as consisting of several adjacent developmental radial progenitor units, disposing their distinct periventricular, intermediate, and superficial strata from the ventricle to the pial surface. It was expected that cell populations belonging to specific progenitor domains would present greater molecular similarity to each other than to neighboring developmental units. In this work, we aim to corroborate the existence of several radial domains in the pallial amygdala at the transcriptomic level. snRNAseq experiments in the amygdala of adult mice of both sexes indicated that at low resolution, the whole pallial amygdala was found to divide into two super-radial domains distinguished by differential expression of Slc17a6 and Slc17a7; the former partly imitates molecularly the subpallial (output) amygdalar regions, whereas the rest of the pallial amygdala is molecularly more akin to the surrounding cortical areas. In addition, our snRNAseq transcriptomic analysis fully supports the postulated amygdalar radial model of four main radial domains. Full article

The organization of consciousness is described through increasingly rich theoretical models. We review evidence that working memory capacity—essential to generating consciousness in the cerebral cortex—is supported by dual limbic memory systems. These dorsal (Papez) and ventral (Yakovlev) limbic networks provide the basis for mnemonic processing and prediction in the dorsal and ventral divisions of the human neocortex. Empirical evidence suggests that the dorsal limbic division is (i) regulated preferentially by excitatory feedforward control, (ii) consolidated by REM sleep, and (iii) controlled in waking by phasic arousal through lemnothalamic projections from the pontine brainstem reticular activating system. The ventral limbic division and striatum, (i) organizes the inhibitory neurophysiology of NREM to (ii) consolidate explicit memory in sleep, (iii) operating in waking cognition under the same inhibitory feedback control supported by collothalamic tonic activation from the midbrain. We propose that (i) these dual (excitatory and inhibitory) systems alternate in the stages of sleep, and (ii) in waking they must be balanced—at criticality—to optimize the active inference that generates conscious experiences. Optimal Bayesian belief updating rests on balanced feedforward (excitatory predictive) and feedback (inhibitory corrective) control biases that play the role of prior and likelihood (i.e., sensory) precision. Because the excitatory (E) phasic arousal and inhibitory (I) tonic activation systems that regulate these dual limbic divisions have distinct affective properties, varying levels of elation for phasic arousal (E) and anxiety for tonic activation (I), the dual control systems regulate sleep and consciousness in ways that are adaptively balanced—around the entropic nadir of E–I criticality—for optimal self-regulation of consciousness and psychological health. Because they are emotive as well as motive control systems, these dual systems have unique qualities of feeling that may be registered as subjective experience. Full article

Background: Anabolic–androgenic steroids (AASs) are commonly used for performance enhancement but have been linked to significant neurobiological consequences. This review explores the impact of AASs on neurochemical pathways, cognitive function, and psychiatric disorders, highlighting their potential neurotoxicity. Methods: A narrative review of current literature was conducted to examine AASs-induced alterations in neurotransmitter systems, structural and functional brain changes, and associated psychiatric conditions. The interplay between AASs use and other substances was also considered. Results: Chronic AASs exposure affects serotonin and dopamine systems, contributing to mood disorders, aggression, and cognitive deficits. Structural and functional changes in the prefrontal cortex and limbic regions suggest long-term neurotoxicity. AASs use is associated with increased risks of depression, anxiety, and psychosis, potentially driven by hormonal dysregulation and neuroinflammation. Co-occurring substance use exacerbates neurocognitive impairments and behavioral disturbances. Discussion: While evidence supports the link between AASs use and neurotoxicity, gaps remain in understanding the precise mechanisms and long-term effects. Identifying biomarkers of brain damage and developing targeted interventions are crucial for mitigating risks. Increased awareness among medical professionals and policymakers is essential to address AASs-related neuropsychiatric consequences. Conclusions: AASs abuse poses significant risks to brain health, necessitating further research and prevention efforts. Evidence-based strategies are needed to educate the public, enhance early detection, and develop effective interventions to reduce the neuropsychiatric burden of AASs use. Full article

Sensory dysregulation represents a core challenge in autism spectrum disorder (ASD), affecting perception, behavior, and adaptive functioning. The brain’s ability to reorganize, known as neuroplasticity, serves as the basic principle for therapeutic interventions targeting these deficits. Neuroanatomical mechanisms include altered connectivity in the sensory and visual cortices, as well as in the limbic system and amygdala, while imbalances of neurotransmitters, in particular glutamate and gamma-aminobutyric acid (GABA), contribute to atypical sensory processing. Traditional therapies used in sensory integration are based on the principles of neuroplasticity. Increasingly, new treatments use this knowledge, and modern therapies such as neurofeedback, transcranial stimulation, and immersive virtual environments are promising in modulating neuronal circuits. However, further research is needed to optimize interventions and confirm long-term effectiveness. This review discusses the role of neuroplasticity in the etiopathogenesis of sensory integration deficits in autism spectrum disorder. The neuroanatomical and neurotransmitter basis of impaired perception of sensory stimuli is considered, and traditional and recent therapies for sensory integration are discussed. Full article

In the last several decades, a number of animal models of neurological diseases have been proposed and validated to one degree or another. This review focuses on the olfactory bulbectomized rodent as a model of major depression, a disorder that, because of its prevalence, has been called the “common cold” of neurological diseases, though the disability it causes is far more profound. After describing the method, a brief history of this model and the various validity claims made for it are discussed. Though a legion of physiological and biochemical sequelae of bulbectomy and other animal models of depression have been reported, the focus of this review is behavioral. Therefore, the neurochemical and molecular aspects of the depression models mentioned in this review will not be explored in depth. Lastly, unresolved questions posed by the bulbectomy model are considered along with its utility in the study of other neurological diseases and its future prospects. Full article

Background: Digital technologies offer innovative opportunities for recovering and maintaining intellectual and mental health. The use of a multitask approach that combines motor component with various cognitive tasks in a virtual environment can optimize cognitive and physical functions and improve the quality of life of cardiac surgery patients. This study aimed to localize current sources of theta and alpha power in patients who have undergone virtual multitask training (VMT) and a control group in the early postoperative period of coronary artery bypass grafting (CABG). Methods: A total of 100 male CABG patients (mean age, 62.7 ± 7.62 years) were allocated to the VMT group (n = 50) or to the control group (n = 50). EEG was recorded in the eyes-closed resting state at baseline (2–3 days before CABG) and after VMT course or approximately 11–12 days after CABG (the control group). Power EEG analysis was conducted and frequency-domain standardized low-resolution tomography (sLORETA) was used to assess the effect of VMT on brain activity. Results: After VMT, patients demonstrated a significantly higher density of alpha-rhythm (7–9 Hz) current sources (t > −4.18; p < 0.026) in Brodmann area 30, parahippocampal, and limbic system structures compared to preoperative data. In contrast, the control group had a marked elevation in the density of theta-rhythm (3–5 Hz) current sources (t > −3.98; p < 0.017) in parieto-occipital areas in comparison to preoperative values. Conclusions: Virtual reality-based multitask training stimulated brain regions associated with spatial orientation and memory encoding. The findings of this study highlight the importance of neural mechanisms underlying the effectiveness of multitask interventions and will be useful for designing and conducting future studies involving VR multitask training. Full article

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article

Background/Objectives: Borderline personality disorder (BPD) is a complex psychiatric condition marked by emotional dysregulation, interpersonal instability, and impulsivity. Despite the advances in psychotherapy and pharmacotherapy, many patients show a partial or unstable response. Recent research suggests that oxytocin, a neuropeptide involved in social cognition and emotional regulation, may offer novel therapeutic avenues. Methods: We systematically synthesize evidence from PubMed, PsycINFO, Web of Science, and Google Scholar on oxytocin’s role in BPD, prioritizing studies on neurobiology, emotion regulation, clinical interventions, and adjunctive therapy models. Thirty studies were included and critically appraised using PRISMA and Cochrane’s tools. Due to methodological heterogeneity, no meta-analysis was conducted; instead, the findings were integrated through a narrative synthesis approach. Results: Evidence supports oxytocin’s modulatory effects on amygdala reactivity, prefrontal–limbic connectivity, and hypothalamic–pituitary–adrenal axis function. Intranasal oxytocin appears beneficial for emotional regulation and interpersonal sensitivity, particularly in individuals with early trauma. The reported effect sizes ranged from small (Cohen’s d ≈ 0.40) to large (d ≈ 0.83), though some trials reported null or adverse effects, such as increased hypermentalization. Heterogeneous responses were influenced by factors such as sex, trauma history, and OXTR gene variants. Conclusions: Although intranasal oxytocin shows promise in modulating core neurobiological systems implicated in BPD and enhancing emotion regulation and social cognition, its clinical effects remain variable and context-dependent. The evidence supports cautious exploration of oxytocin as an adjunct to psychotherapeutic interventions rather than as a standalone treatment. Future research should focus on biomarker-informed, stratified trials that account for trauma history, genetic variation, and sex differences to clarify its therapeutic potential. Full article