Search Results (106)

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory dermatosis of the pilosebaceous unit characterized by nodules, abscesses, and dermal tunnels. Recent transcriptomic studies have implicated dysregulation of innate and adaptive immune responses, epidermal barrier dysfunction, and systemic metabolic alterations. This review synthesizes findings from 16 studies investigating the HS transcriptome using bulk and single-cell RNA sequencing. Differential gene expression analyses revealed extensive upregulation of inflammatory cytokines and chemokines, particularly in lesional and perilesional skin. These changes were also mirrored in non-lesional skin, suggesting diffuse immune dysregulation beyond visibly affected areas. Downregulated pathways include those involved in lipid metabolism, muscle contraction, and neuronal signaling, potentially linking HS to obesity, metabolic syndrome, and neuropsychiatric comorbidities. Single-cell transcriptomics confirmed the enrichment of keratinocytes and immune cells (B cells, plasma cells, M1 macrophages, and T cells) with proinflammatory profiles in HS lesions. Keratinocyte dysfunction further implicated a compromised epidermal barrier in disease pathogenesis. While transcriptomic studies have advanced mechanistic understanding and highlighted therapeutic targets—such as the IL-1β–TH17 axis and B cell signaling pathways—methodological heterogeneity limits cross-study comparisons. Integration of multi-omics data and standardized phenotyping will be essential to identify robust biomarkers, stratify HS subtypes, and guide personalized therapeutic approaches. Full article

Parkinson’s disease (PD) is a progressive, multisystemic α-synucleinopathy, recognized as the second most prevalent neurodegenerative disorder globally. Its neuropathology is characterized by the degeneration of dopaminergic neurons, particularly in the substantia nigra pars compacta (SNpc), and the intraneuronal accumulation of α-synuclein-forming Lewy bodies. Oxidative stress is a key contributor to PD pathogenesis. Thioredoxin-interacting protein (TXNIP) is a crucial regulator of cellular redox balance, inhibiting the antioxidant function of thioredoxin. This pilot study aimed to investigate the protein expression and localization of TXNIP in the SNpc of PD patients compared to healthy controls. We performed immunohistochemical analyses on 12 post-mortem human brain sections (formalin-fixed, paraffin-embedded) from six subjects with PD and six healthy controls. The study was performed on PD subjects with Braak stage 6. Our findings revealed that in control samples, TXNIP protein was distinctly and closely associated with neuromelanin (NM) pigment within the cytoplasm of SNpc dopaminergic neurons. Conversely, in PD samples, there was a markedly weak cytoplasmic expression of TXNIP, and critically, this association with NM pigment was absent. Furthermore, PD samples exhibited a significant reduction in both dopaminergic neurons and NM content, consistent with advanced disease. These findings, which mirror previous transcriptomic data showing TXNIP gene under-expression in the same subjects, suggest that altered TXNIP expression and localization in SNpc dopaminergic neurons are features of late-stage PD, potentially reflecting neuronal dysfunction and loss. Full article

Zebrafish (Danio rerio) combine accessible behavioral phenotypes with conserved neurochemical pathways and molecular features of vertebrate brain function, positioning them as a powerful model for investigating early neurodegenerative processes and screening neuroprotective strategies. In this context, integrated behavioral and proteomic analyses provide valuable insights into the initial pathophysiological events shared by conditions such as Parkinson’s disease and related disorders—including mitochondrial dysfunction, oxidative stress, and synaptic impairment—which emerge before overt neuronal loss and offer a crucial window to understand disease progression and evaluate therapeutic candidates prior to irreversible damage. To investigate this early window of dysfunction, zebrafish larvae were exposed to 500 μM 1-methyl-4-phenylpyridinium (MPP⁺) from 1 to 5 days post-fertilization and evaluated through integrated behavioral and label-free proteomic analyses. MPP⁺-treated larvae exhibited hypokinesia, characterized by significantly reduced total distance traveled, fewer movement bursts, prolonged immobility, and a near-complete absence of light-evoked responses—mirroring features of early Parkinsonian-like motor dysfunction. Label-free proteomic profiling revealed 40 differentially expressed proteins related to mitochondrial metabolism, redox regulation, proteasomal activity, and synaptic organization. Enrichment analysis indicated broad molecular alterations, including pathways such as mitochondrial translation and vesicle-mediated transport. A focused subset of Parkinsonism-related proteins—such as DJ-1 (PARK7), succinate dehydrogenase (SDHA), and multiple 26S proteasome subunits—exhibited coordinated dysregulation, as visualized through protein–protein interaction mapping. The upregulation of proteasome components and antioxidant proteins suggests an early-stage stress response, while the downregulation of mitochondrial enzymes and synaptic regulators reflects canonical PD-related neurodegeneration. Together, these findings provide a comprehensive functional and molecular characterization of MPP⁺-induced neurotoxicity in zebrafish larvae, supporting its use as a relevant in vivo system to investigate early-stage Parkinson’s disease mechanisms and shared neurodegenerative pathways, as well as for screening candidate therapeutics in a developmentally responsive context. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is known to affect multiple organ systems, including the respiratory tract and nervous and ocular systems. This retrospective study aimed to characterize the spatiotemporal distribution of viral antigen and associated pathological changes in the nose, lungs, brain, and eyes of K18-hACE2 mice intranasally infected with SARS-CoV-2. Using histology and immunohistochemistry, tissues were examined at 3, 6, and 7/8 days post-infection (dpi). In addition, lung and brain tissues were analyzed by means of RT-qPCR to determine viral RNA titers. Viral antigen was most pronounced in the nose, brain, and lung at 3, 6, and 7/8 dpi, respectively, whereas viral antigen was detected at 6 and 7/8 dpi in the retina. Quantitative PCR confirmed increasing viral RNA levels in both lung and brain, peaking at 7/8 dpi. Nasal and lung inflammation mirrored viral antigen distribution and localization. In the brain, the predominantly basal viral spread correlated with lymphohistiocytic meningoencephalitis, neuronal vacuolation, and altered neurofilament immunoreactivity. Retinal ganglion cells showed viral antigen expression without associated lesions. Microglial activation was evident in both the optic chiasm and the brain. These findings highlight the K18-hACE2 model’s utility for studying extrapulmonary SARS-CoV-2 pathogenesis. Understanding the temporal and spatial dynamics of viral spread enhances insights into SARS-CoV-2 neurotropism and its clinical manifestations. Full article

Empathy has been linked to enhanced processing of social information, yet the neurophysiological correlates of such individual differences remain underexplored. Objectives: The aim of this study was to investigate how individual differences in trait empathy are reflected in oscillatory brain activity during the perception of non-verbal social cues. Methods: In this EEG study involving 30 participants, we examined spectral and time–frequency dynamics associated with trait empathy during a visual task requiring the interpretation of others’ body gestures. Results: FFT Power spectral analyses (applied to alpha/mu, beta, high beta, and gamma bands) revealed that individuals with high empathy quotients (High-EQ) exhibited a tendency for increased beta-band activity over frontal regions and markedly decreased alpha-band activity over occipito-parietal areas compared to their low-empathy counterparts (Low-EQ), suggesting heightened attentional engagement and reduced cortical inhibition during social information processing. Similarly, time–frequency analysis using Morlet wavelets showed higher alpha power in Low-EQ than High-EQ people over occipital sites, with no group differences in mu suppression or desynchronization (ERD) over central sites, challenging prior claims linking mu ERD to mirror neuron activity in empathic processing. These findings align with recent literature associating frontal beta oscillations with top-down attentional control and emotional regulation, and posterior alpha with vigilance and sensory disengagement. Conclusions: Our results indicate that empathic traits are differentially reflected in anterior and posterior oscillatory dynamics, supporting the notion that individuals high in empathy deploy greater cognitive and attentional resources when decoding non-verbal social cues. These neural patterns may underlie their superior ability to interpret body language and mental states from visual input. Full article

Mirror neurons (MNs), a set of neurons that are activated during the processes of observation and execution of actions, have drawn significant attention in the research of neurodegenerative and psychological disorders. Research in the field of Autism Spectrum Disorder (ASD) and schizophrenia demonstrates evidence in favour of common underlying neural mechanisms underlying the two conditions, especially with respect to mu rhythm suppression, a proxy for MN activation and socio-cognitive impairments. This paper aims to review the most recent studies on the neurological underpinnings of social cognition deficits and cognitive discrepancies shared by ASD and schizophrenia, as detected by measuring the functionality and activation of the mirror neuron system. The findings of the review reveal a lack of consensus with respect to the validity of the “broken mirror” theory. The review also shows that further research is warranted to shed light on the implications of mirror neuron dysfunction in neuropsychiatric conditions and assist the development of technological interventions and treatments. Full article

Oligodendrocyte precursor cells (OPCs) are a dynamic and heterogeneous population of glial cells essential for brain development and myelination. Beyond their well-established role in oligodendrogenesis, emerging evidence suggests that OPCs contribute to synaptic regulation, neuronal communication, and brain plasticity. Recent studies have increasingly implicated OPC dysfunction in the pathophysiology of psychiatric disorders, particularly schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). This narrative review integrates clinical, genetic, transcriptomic, and histological findings to examine the role of OPC alterations in mental illnesses. In SCZ, OPC abnormalities predominantly affect myelination, but recent data also suggest deficits in non-canonical functions, including neuron–OPC communication. Findings in BD largely mirror those in SCZ, implying shared OPC-related mechanisms across these disorders. In contrast, OPC involvement in MDD appears more complex, with evidence supporting both myelination deficits and non-canonical dysfunctions, such as impaired neuro–glial interactions and perineuronal network alterations. The developmental timing of OPC dysfunction may represent a common denominator underlying psychiatric disorders, as early-life stress and neurodevelopmental disturbances have been linked to OPC impairments. Moreover, given the shared developmental origins of OPCs and parvalbumin-positive interneurons, disruptions in their mutual interactions may contribute to broader neural network dysregulation. Despite these insights, the field remains in its infancy. Future studies integrating independent human cohorts with robust preclinical models are needed to clarify the extent of OPC involvement in psychiatric pathophysiology. Understanding OPC dysfunction may reveal novel biomarkers and open new avenues for individualized therapeutic interventions and preventive strategies in mental health. Full article

Hepatitis E, caused by the hepatitis E virus (HEV), is a zoonotic disease that extends beyond hepatocellular necrosis to replicate in multiple organs. While most infections are self-limiting, HEV infection during pregnancy is associated with severe outcomes, including acute liver failure, preterm delivery, and miscarriage, with the mechanisms underlying this high pathogenicity remaining poorly understood. This study established a pregnant tree shrew model with a late-stage HEV infection and a cellular model using zoonotic HEV genotypes GT3 and GT4 to investigate the effects of estrogen on HEV replication. Results showed that negative-strand RNA detection revealed replicative intermediates in feces and tissues during the acute phase, with peak viral loads occurring within one week and the highest titers in bile. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels rose at 3 days post-inoculation (DPI), peaking at 7 DPI. Elevated estrogen levels post-miscarriage correlated with increased viral loads, a trend mirrored in cell culture models showing linear relationships between estrogen and viral replication. Histopathology demonstrated viral hepatitis lesions in liver tissues and abnormalities in the uterus, ovaries, and brain, including hydropic degeneration, neuronal disruption, and granulosa cell necrosis. This study developed a pregnant tree shrew model for HEV infection, providing a robust tool for exploring pathogenic mechanisms during pregnancy and genotype-specific differences in zoonotic HEV pathogenicity. These findings offer new insights into the role of estrogen in HEV replication and its contribution to adverse pregnancy outcomes. Full article

Background/Objectives: Action observation therapy (AOT) has gained attention as a rehabilitation method for motor function recovery following nerve injury. Although the total observation time and daily session duration have been studied, the effective observation duration per trial remains unclear. This study examined the effect of different observation durations on manual dexterity, mirror neuron system activity, and subjective psychomotor effort in healthy adults. Methods: Twenty-four healthy right-handed adults participated in this crossover study under four conditions: observing ball rotations with the dominant hand for one, two, or three minutes, or geometric patterns (control) for two minutes. The outcomes included maximum rotations and errors by both hands during a ball rotation task and interpersonal motor resonance (IMR), indicating mirror neuron system activity. These measures were compared before and after intervention. Subjective ratings of concentration, physical fatigue, and mental fatigue were assessed post-intervention. Results: Rotation performance significantly increased for the intervention hand after a 2 min observation and showed a notable effect (p = 0.113, r = 0.48) for the non-intervention hand after a 3 min observation compared to the control. The IMR was significantly greater during the 2 min observation than in the control. Compared to the 1 min observation, the 2 min and 3 min observations resulted in higher mental fatigue, and the 3 min observation showed lower concentration levels. Conclusions: These findings indicate that the observation duration has varying effects on manual dexterity and mirror neuron system activity, with optimal effects observed at specific time intervals while also highlighting the relationship between observational learning and psychomotor effort. Full article

Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and cognitive or motor decline, often underpinned by pathological protein misfolding and aggregation. Emerging evidence suggests a potential mechanistic link between chronic pain and NDs, with persistent pain contributing to neuroinflammatory states and protein homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis that protein misfolding and aggregation serve as a mechanistic bridge between chronic pain and neurodegeneration. We systematically examine molecular pathways of protein misfolding, proteostasis dysfunction in chronic pain, and shared neuroimmune mechanisms, highlighting prion-like propagation of misfolded proteins, chronic neuroinflammation, and oxidative stress as common denominators. We further discuss evidence from experimental models and clinical studies linking chronic pain to accelerated neurodegenerative pathology—including tau accumulation, amyloid dysregulation, and microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting protein aggregation, enhancing chaperone function, modulating the unfolded protein response (UPR), and attenuating glial activation are explored as potential strategies to mitigate chronic pain and possibly slow neurodegeneration. Understanding this intersection not only elucidates chronic pain’s role in cognitive decline but also suggests that interventions addressing proteostasis and inflammation could yield dual benefits in pain management and neurodegenerative disease modification. Full article

Botulinum toxin type A (BoNT-A) induces a bilateral analgesic effect following unilateral injection in rodent bilateral or mirror pain models. This occurs either by indirect plasticity-related actions, or by the toxin’s direct central action in bilateral spinal circuits. Herein, we aimed to resolve this question by assessing the role of trans-synaptic toxin traffic in a bilateral inflammatory pain model. The analgesic effect of the toxin was examined in rats pre-treated with unilateral intraplantar BoNT-A (7 U/kg) and subsequently challenged with bilateral carrageenan-evoked hind-paw inflammation (2%, 50 µL/paw, 6 days post BoNT-A). Specific neutralizing antitoxin injected into the lumbar intrathecal space (2 IU, 24 h post BoNT-A), aimed at preventing the spinal trans-synaptic traffic of BoNT-A, abolished its bilateral analgesic effect. The toxin trans-synaptic effect was associated with reduced c-Fos neuronal activation and BoNT-A-mediated cleavage of synaptosomal-associated protein 25 (SNAP-25) in the bilateral dorsal horn. Here, we showed that, in bilaterally occurring pain, BoNT-A exerts a direct contralateral analgesic action extending beyond the level of the dorsal root ganglion sensory neuron that directly links the hindlimb injection site to the primary sensory region. This points to the crucial role of the toxin’s central trans-synaptic traffic, and its direct action at propriospinal nociceptive circuits in its pain-relieving efficacy. Full article

Background/Objectives. Mirror properties of the action observation network (AON) can be modulated through Hebbian-like associative plasticity using paired associative stimulation (PAS). We recently introduced a visuomotor protocol (mirror–PAS, m-PAS) that pairs transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) with visual stimuli of ipsilateral (to TMS) movements, leading to atypical corticospinal excitability (CSE) facilitation (i.e., motor resonance) during PAS-conditioned action observation. While m-PAS aftereffects are robust, little is known about markers of associative plasticity during its administration and their predictive value for subsequent motor resonance rewriting. The present study aims to fill this gap by investigating CSE modulations during m-PAS and their relationship with the protocol’s aftereffects. Methods. We analyzed CSE dynamics in 81 healthy participants undergoing the m-PAS before and after passively observing left- or right-hand index finger movements. Here, typical and PAS-conditioned motor resonance was assessed with TMS over the right M1. We examined CSE changes during the m-PAS and used linear regression models to explore their relationship with motor resonance modulations. Results. m-PAS transiently reshaped both typical and PAS-induced motor resonance. Importantly, we found a gradual increase in CSE during m-PAS, which predicted the loss of typical motor resonance but not the emergence of atypical responses after the protocol’s administration. Conclusions. Our results suggest that the motor resonance reshaping induced by the m-PAS is not entirely predictable by CSE online modulations. Likely, this rewriting is the product of a large-scale reorganization of the AON rather than a phenomenon restricted to the PAS-stimulated motor cortex. This study underlines that monitoring CSE during non-invasive brain stimulation protocols could provide valuable insight into some but not all plastic outcomes. Full article

Alzheimer’s disease (AD) is the most common cause of dementia, and no cure is currently available. The β-amyloid cascade of AD and neurofibrillary tangles are the basis of the current understanding of AD pathogenesis, driving drug investigation and other discoveries. Up until now, no AD models have entirely validated the β-amyloid cascade hypothesis. AD models must be capable of recapitulating the critical events of this pathology, including β-amyloid plaques and neurofibrillary tangles. The development of plaques is probably derived from the amyloid precursor protein (APP) and presenilin 1 (PS1) familial Alzheimer’s disease (FAD) mutations, while the tangle-like pathology is determined by tau mutations. Transgenic mouse models struggle to replicate the entire spectrum of AD, particularly neuronal death stemming from β-amyloid and tau pathologies. Furthermore, the success of these transgenic mice often relies on the overexpression of APP transgenes enclosing FAD-associated mutations at levels beyond physiological. Ultimate species-specific discrepancies in genome and protein composition between the human and the mouse may hinder the accurate recapitulation of AD pathological events in mouse models. Although none of the AD models fully mirrors human pathology, these experimental in vivo animal models have provided valuable insights into β-amyloid toxicity and the overall pathophysiological basis of AD. Therefore, these experimental models have been widely used in the preclinical evaluation of therapeutic strategies and have played a pivotal role in the development of immunotherapies for AD. In this review, we sum up the main transgenic mouse models used for AD research, whether they are APP mutation-based mice, APP plus presenilin mutation-based mice, or tau mutation-based mice. The specific characteristics of each mouse model and the significance of their use for AD research, focusing on their current advantages and disadvantages, as well as on the progress made and the forthcoming challenges in replicating this neurodegenerative disease, are also highlighted. Full article

Background: Parkinson’s disease is primarily characterized by the degeneration of motor neurons, leading to significant impairments in movement. Initially, physical therapy was predominantly employed to address these motor issues through targeted rehabilitation exercises. However, recent research has indicated that cognitive training can enhance the quality of life for patients with Parkinson’s. Consequently, some researchers have posited that the simultaneous engagement in computer-assisted motor and cognitive dual-task (CADT) may yield superior therapeutic outcomes. Methods: A comprehensive literature search was performed across various databases, and studies were selected following PRISMA guidelines, focusing on CADT rehabilitation interventions. Results: Dual-task training enhances Parkinson’s disease (PD) rehabilitation by automating movements and minimizing secondary task interference. The inclusion of a sensor system provides real-time feedback to help patients make immediate adjustments during training. Furthermore, CADT promotes more vigorous participation and commitment to training exercises, especially those that are repetitive and can lead to patient boredom and demotivation. Virtual reality-tailored tasks, closely mirroring everyday challenges, facilitate more efficient patient adaptation post-rehabilitation. Conclusions: Although the current studies are limited by small sample sizes and low levels, CADT rehabilitation presents as a significant, effective, and potential strategy for PD. Full article

Introduction: Impairments in social cognition and cognitive deficits in bipolar disorder (BD) offer insights into the disorder’s progression. Understanding how interventions impact both cognitive and emotional aspects of social cognition is essential. This study examines the effects of virtual reality (VR) cognitive remediation on cognitive skills, stratified by age, in the early stages of the disorder. Methods: A secondary analysis of a randomized controlled trial (RCT) compared the efficacy of VR cognitive remediation on cognitive skills between young adults (≤58 years) and older adults (≥59 years) in the experimental group with BD. Results: The experimental group included 39 participants: 24 ≤ 58 years and 15 ≥ 59 years. Young adults showed greater improvement in the Digit Span Backward (0.37 ± 0.35 vs. 0.07 ± 0.26, F = 9.882, p = 0.020) and Digit Symbol tests (3.84 ± 3.05 vs. 1.16 ± 3.8, F = 5.895, p = 0.020). Older adults improved more in the Frontal Assessment Battery (1.00 ± 0.95 vs. 0.54 ± 0.21, F = 5.295, p = 0.027), Matrix test (0.58 ± 0.35 vs. 0.37 ± 0.26, F = 4.606, p = 0.038), and Test of Tale (0.81 ± 0.36 vs. 0.42 ± 0.38, F = 10.115, p = 0.003). Conclusions: Young adults improved more in complex cognitive tasks, while older adults showed better results in simpler tasks. The effectiveness of VR may be due to hyperstimulation of mirror neurons. Further studies are needed to confirm these findings. Full article