Search Results (45)

Zebrafish is a well-recognized model for studying human genetic disorders. Recently, we proposed the homozygous cdkl5^sa21938 mutant zebrafish as a model of CDKL5 deficiency disorder (CDD), a developmental epileptic encephalopathy with diverse symptoms. This study aimed to explore Cdkl5-associated molecular mechanisms in zebrafish and assess their similarity to those in mammals. We conducted RNA sequencing on whole cdkl5^−/− zebrafish and wild-type siblings at 5 and 35 days post-fertilization (dpf) to compare their gene expression profiles. Most significant differentially expressed genes (DEGs) were related to muscle, neuronal, and visual systems which are affected in CDD. Gene Ontology analysis revealed downregulated DEGs enriched in muscle development, extracellular matrix, and actin cytoskeleton functions at both stages, while upregulated DEGs were enriched in eye development functions at 35 dpf. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed enrichment of downregulated DEGs in focal adhesion and extracellular matrix (ECM)-receptor interaction pathways at both stages. Neuronal development DEGs were mainly downregulated at both stages, while synaptic signaling DEGs were upregulated at 35 dpf. Crossing cdkl5^−/− mutants with the Hb9:GFP transgenic line showed fewer motor neuron cells with shorter axons compared to the wild type, which may explain the impaired motor phenotype observed in zebrafish and CDD patients. Moreover, we identified key downregulated DEGs related to cartilage development at both stages and bone development at 35 dpf, potentially explaining the skeletal defects seen in zebrafish and CDD individuals. In conclusion, Cdkl5 loss in zebrafish leads to dysregulation of genes involved in CDKL5-associated functions in mammals, providing new insights into its less studied functions and phenotypes. Full article

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition that develops in response to traumatic events. The endocannabinoid, glutamatergic, and GABAergic systems play crucial roles in the neurobiological mechanisms of PTSD. Both the endocannabinoid, glutamatergic, and GABAergic systems are involved in synaptic remodeling and neuronal differentiation, ensuring efficient information transmission in the brain. Their interplay influences motivation, behavior, sensory perception, pain regulation, and visual processing. Additionally, these systems regulate processes such as cellular proliferation, adhesion, apoptosis, and immune responses. This article explores the involvement of the endocannabinoid, glutamatergic, and GABAergic systems in PTSD pathogenesis. A literature review was conducted on studies examining the relationship between the endocannabinoid, glutamatergic, and GABAergic systems in PTSD. Relevant publications were sourced from the Web of Science and Scopus databases, covering research up to 29 February 2025. Neurobiological mechanisms underlying PTSD may share common pathways with other mental and somatic disorders, particularly those involving inflammatory processes. The identification of biomarkers is crucial for assessing PTSD risk and implementing targeted interventions to improve patient outcomes. A deeper understanding of these mechanisms could enhance therapeutic strategies, ultimately improving the quality of life for individuals affected by PTSD. Full article

Background: The diagnosis of multiple sclerosis (MS) relies on identifying neurological signs and symptoms, supported by evidence of central nervous system (CNS) dissemination of lesions across time and space. The visual pathway is commonly involved in MS, with a frequent involvement of optic neuritis (ON) episodes. Our study aims to assess the relationship between neuronal damage and optic nerve demyelination by analyzing the latency and amplitude of the p100 wave complex using visual evoked potentials (VEPs). Methods: We conducted a retrospective longitudinal study, analyzing VEP records of 15 patients with recurrent remissive MS at baseline, 5, 10, 15, and 19 years. Results: In 30 eyes we observed an increase in p100 wave latency at 5-years by 14.35 ± 4.47 ms (p = 0.003), at 10-years by 19.26 ± 4.87 ms (p < 0.0005) and a decrease in amplitude by 2.29 ± 0.52 mV (p < 0.0005) when comparing to baseline values. At 15-years, 24 eyes presented an increase in latency of 31.39 ± 7.8 ms (p = 0.001) and a decrease in amplitude of 2.51 ± 0.6 mV (p < 0.0005) compared to baseline, while at 19-years, 10 eyes presented an increase in p100 wave latency of 53.45 ± 18.42 ms (p = 0.018) and a further decrease in amplitude of 4.06 ± 1.32 mV (p = 0.014). We found correlations between the p100 wave latency and amplitude at baseline, 15-year, and 19-year follow-ups, increasing from a low negative (r = −0.43) to medium negative (r = −0.502) and finally high negative (r = −0.906) correlation. Conclusions: VEPs have long been acknowledged for their ability to detect both clinical and subclinical lesions in MS cases. Our study offers new insight into the relationship between demyelination and axonal degeneration observed when analyzing the latency and amplitude of the p100 wave complex during VEP in a longitudinal analysis. Full article

Background/Objectives: This study explores the micro-structure of celiac ganglia using two-photon microscopy (TPM) to highlight histological features in neurodegenerative conditions. Neurodegenerative diseases like Parkinson’s disease (PD) are linked to dysautonomia, impacting autonomic regulation and leading to significant gastrointestinal and autonomic symptoms. Our research compares imaging results from TPM and SHG microscopy, visualizing neuronal integrity, collagen distribution, and the architectural organization of celiac ganglia. SHG specifically allows detailed imaging of collagen fibers and neuronal structures, revealing alterations in collagen density and organization that correlate with dysautonomia. Methods: The cross-sectional study was conducted at “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest, Romania, involving 70 participants diagnosed with PD (Hoehn and Yahr stages 2–4), including 35 with dysautonomia and 35 without. We utilized samples from PD patients with and without dysautonomia, applying immunohistochemical markers for sympathetic neurons. Results: Our findings reveal significant pathological changes in neuronal structure and collagen architecture. Immunohistochemical markers (neuropeptide Y, neurofilament heavy chain (NF-H), and tyrosine hydroxylase) were employed to characterize sympathetic neurons, while TPM and SHG provided high-resolution imaging of neuronal integrity and extracellular matrix composition. Conclusions: These imaging techniques present a promising tool for early diagnosis and assessment of neurodegeneration and dysautonomia in PD patients. Moreover, these techniques may represent a critical bridge between histopathological findings and clinical manifestations, underscoring their role in enhancing our understanding of neurodegeneration and autonomic dysfunction in Parkinson’s disease. Full article

Background: Schizophrenia is a complex disorder characterized by disruptions in cognition, behavior, and emotions. Extensive research has uncovered alterations in a single modality (either the brain structure or function) in schizophrenia. However, the limitation is that a single modality could not offer a synchronous result between the brain structure and function because of different samples. Here, a multiparametric approach is essential to understand the common and distinct alterations between the brain structure and function in schizophrenia. Methods: We analyzed structural and functional magnetic resonance imaging data from 146 participants (72 individuals with schizophrenia and 74 healthy controls). Individual morphological similarity and functional connectivity gradients were computed using a nonlinear dimensionality reduction technique with diffusion map embedding. Furthermore, to understand how the alterations may be related to genetic underpinnings, gene expression enrichment analyses were conducted using Allen Brain Human Atlas and GOrilla. Results: Compared with controls, patients with schizophrenia had reduced scores on the principal functional gradient of the visual network and elevated scores on the principal functional gradient of the limbic network, the frontoparietal control network, and the default mode network. Additionally, the main functional gradient in individuals with schizophrenia showed compression along the primary axis compared to the healthy control group. These changes were linked to genes involved in synaptic signaling and neuronal development. Conclusions: These results indicate connectome gradient dysfunction in schizophrenia and its linkage with gene expression profiles, supporting widespread network-level abnormalities. The integration of neuroimaging provides insight into the neurobiological underpinnings and potential biomarkers for treatment evaluation in this disorder. Full article

The convolutional neural network (CNN) was initially inspired by the physiological visual system, and its structure has become increasingly complex after decades of development. Although CNN architectures now have diverged from biological structures, we believe that the mechanism of feature extraction in the visual system can still provide valuable insights for enhancing CNN robustness and stability. In this study, we investigate the mechanism of neuron orientation selectivity and develop an artificial visual system (AVS) referring to the structure of the primary visual system. Through learning on an artificial object orientation dataset, AVS acquires orientation extraction capabilities. Subsequently, we employ the pre-trained AVS as an information pre-processing block at the front of CNNs to regulate their preference for different image features during training. We conducted a comprehensive evaluation of the AVS–CNN framework across different image tasks. Extensive results demonstrated that the CNNs enhanced by AVS exhibit significant model stability enhancement and error rate decrease on noise data. We propose that incorporating biological structures into CNN design still holds great potential for improving overall performance. Full article

Background/Objectives: High-intensity interval training (HIIT) alternates short periods of intense exercise with recovery, effectively enhancing cardiorespiratory fitness, endurance, and strength in various populations. Concurrently, brain-derived neurotrophic factor (BDNF) supports neuronal resilience and activity-dependent plasticity, which are vital for learning and memory. This study aims to systematically review changes in BDNF levels in response to HIIT, with three primary objectives: evaluating the benefits of HIIT for BDNF modulation, assessing methodological quality and the risk of bias in reviewed studies, and identifying patterns in BDNF response based on HIIT protocols and population characteristics. Methods: Comprehensive database searches were conducted in PubMed and SPORTDiscus to identify relevant studies published up to April 2024. Given the diversity in study designs and outcomes, a narrative synthesis was performed rather than a meta-analysis. Bias was evaluated using visualization tools such as RobVis, and the review was conducted by a single researcher, which may limit its comprehensiveness. Results: Twelve studies met the inclusion criteria, with most indicating significant increases in BDNF levels post-HIIT, suggesting HIIT’s potential to enhance neuroplasticity and cognitive functions. However, variations in BDNF responses were observed across different HIIT protocols and study populations. Some studies reported decreases or no change in BDNF levels, reflecting the complex regulation of BDNF influenced by factors such as exercise intensity, duration, and individual variability. Conclusions: HIIT shows promise as an intervention for increasing BDNF levels, with potential benefits for brain health and cognitive function. These findings underscore the need for further research to confirm the optimal conditions under which HIIT can effectively enhance neurological outcomes. Future studies should explore standardized HIIT protocols and the long-term impact of HIIT on BDNF and neuroplasticity. Full article

Animals utilize their well-evolved dynamic vision systems to perceive and evade collision threats. Driven by biological research, bio-inspired models based on lobula giant movement detectors (LGMDs) address certain gaps in constructing artificial collision-detecting vision systems with robust selectivity, offering reliable, low-cost, and miniaturized collision sensors across various scenes. Recent progress in neuroscience has revealed the energetic advantages of dendritic arrangements presynaptic to the LGMDs, which receive contrast polarity-specific signals on separate dendritic fields. Specifically, feed-forward inhibitory inputs arise from parallel ON/OFF pathways interacting with excitation. However, none of the previous research has investigated the evolution of a computational LGMD model with feed-forward inhibition (FFI) separated by opposite polarity. This study fills this vacancy by presenting an optimized neuronal model where FFI is divided into ON/OFF channels, each with distinct synaptic connections. To align with the energy efficiency of biological systems, we introduce an activation function associated with neural computation of FFI and interactions between local excitation and lateral inhibition within ON/OFF channels, ignoring non-active signal processing. This approach significantly improves the time efficiency of the LGMD model, focusing only on substantial luminance changes in image streams. The proposed neuronal model not only accelerates visual processing in relatively stationary scenes but also maintains robust selectivity to ON/OFF-contrast looming stimuli. Additionally, it can suppress translational motion to a moderate extent. Comparative testing with state-of-the-art based on ON/OFF channels was conducted systematically using a range of visual stimuli, including indoor structured and complex outdoor scenes. The results demonstrated significant time savings in silico while retaining original collision selectivity. Furthermore, the optimized model was implemented in the embedded vision system of a micro-mobile robot, achieving the highest success ratio of collision avoidance at 97.51% while nearly halving the processing time compared with previous models. This highlights a robust and parsimonious collision-sensing mode that effectively addresses real-world challenges. Full article

Background: Epilepsy surgery for extratemporal lobe epilepsy (ETLE) is challenging, particularly when MRI findings are non-lesional and seizure patterns are complex. Invasive diagnostic techniques are crucial for accurately identifying the epileptogenic zone and its relationship with surrounding functional tissue. Microscope-based augmented reality (AR) support, combined with navigation, may enhance intraoperative orientation, particularly in cases involving subtle or indistinct lesions, thereby improving patient outcomes and safety (e.g., seizure freedom and preservation of neuronal integrity). Therefore, this study was conducted to prove the clinical advantages of microscope-based AR support in ETLE surgery. Methods: We retrospectively analyzed data from ten patients with pharmacoresistant ETLE who underwent invasive diagnostics with depth and/or subdural grid electrodes, followed by resective surgery. AR support was provided via the head-up displays of the operative microscope, with navigation based on automatic intraoperative computed tomography (iCT)-based registration. The surgical plan included the suspected epileptogenic lesion, electrode positions, and relevant surrounding functional structures, all of which were visualized intraoperatively. Results: Six patients reported complete seizure freedom following surgery (ILAE 1), one patient was seizure-free at the 2-year follow-up, and one patient experienced only auras (ILAE 2). Two patients developed transient neurological deficits that resolved shortly after surgery. Conclusions: Microscope-based AR support enhanced intraoperative orientation in all cases, contributing to improved patient outcomes and safety. It was highly valued by experienced surgeons and as a training tool for less experienced practitioners. Full article

Over the last two decades, animal models have been used to evaluate the physiological and cognitive effects of mobile phone exposure. Here, we used a head-only exposure system in rats to determine whether exposure to 900 MHz GSM electromagnetic fields (EMFs) induces regional changes in neuronal activation as revealed by c-Fos imaging. In a first study, rats were exposed for 2 h to brain average specific absorption rates (BASARs) ranging from 0.5 to 6 W/kg. Changes in neuronal activation were found to be dose-dependent, with significant increases in c-Fos expression occurring at BASAR of 1 W/kg in prelimbic, infralimbic, frontal, and cingulate cortices. In a second study, rats were submitted to either a spatial working memory (WM) task in a radial maze or a spatial reference memory (RM) task in an open field arena. Exposures (45 min) were conducted before each daily training session (BASARs of 1 and 3.5 W/kg). Control groups included sham-exposed and control cage animals. In both tasks, behavioral performance evolved similarly in the four groups over testing days. However, c-Fos staining was significantly reduced in cortical areas (prelimbic, infralimbic, frontal, cingulate, and visual cortices) and in the hippocampus of animals engaged in the WM task (BASARs of 1 and 3.5 W/kg). In the RM task, EMF exposure-induced decreases were limited to temporal and visual cortices (BASAR of 1 W/kg). These results demonstrate that both acute and subchronic exposures to 900 MHz EMFs can produce region-specific changes in brain activity patterns, which are, however, insufficient to induce detectable cognitive deficits in the behavioral paradigms used here. Full article

Carotenoids, having strong antioxidant properties, have been associated with neurodegenerative conditions like dementia and glaucoma, characterized by neuronal loss leading to cognitive and visual dysfunction. Therefore, carotenoids have attracted attention as factors predictive of the onset and progression of these neurodegenerative diseases. However, the impact of carotenoids on cognitive impairment and glaucomatous visual field defects remains unexplored. We conducted a retrospective, observational clinical study to investigate the association between skin carotenoid (SC) levels and cognitive impairment, as screened by the Mini-Cog test, in glaucoma patients. The study included 406 participants and 812 eyes were examined (average age: 69.7 ± 11.4 years; 228 men, 178 women) with various types of glaucoma: primary open angle (57.6%), exfoliation (18.6%), and other types (23.8%). SC levels were estimated via pressure-mediated reflection spectroscopy. Mixed-effects regression models were utilized to examine the relationship between SC levels, visual field defects, and Mini-Cog results. Of the participants, 28 (6.9%) tested positive on the Mini-Cog, suggesting cognitive impairment. The average SC level in the Mini-Cog positive group was significantly lower than in the negative group (269.5 ± 86.4 A.U. vs. 329.2 ± 120.4 A.U., respectively; p = 0.01). Additionally, the visual field mean deviation (MD) in the Mini-Cog positive group was notably worse than that in the negative group (−19.64 ± 9.07 dB vs. −12.46 ± 9.28 dB, respectively; p < 0.0001). The mixed-effects regression analysis revealed a significant association between Mini-Cog positivity and lower SC levels (p = 0.0006), although SC levels did not significantly correlate with MD (p = 0.3). Our findings suggest that cognitive impairment in glaucoma patients is associated with lower SC levels, underscoring the potential benefits of maintaining carotenoid levels to slow cognitive function decline. The protective role of carotenoids in glaucoma merits further investigation. Full article

The 5xFAD transgenic mouse model widely used in Alzheimer’s disease (AD) research recapitulates many AD-related phenotypes with a relatively early onset and aggressive age-dependent progression. Besides developing amyloid peptide deposits alongside neuroinflammation by the age of 2 months, as well as exhibiting neuronal decline by the age of 4 months that intensifies by the age of 9 months, these mice manifest a broad spectrum of behavioural impairments. In this review, we present the extensive repertoire of behavioural dysfunctions in 5xFAD mice, organised into four categories: motor skills, sensory function, learning and memory abilities, and neuropsychiatric-like symptoms. The motor problems, associated with agility and reflex movements, as well as balance and coordination, and skeletal muscle function, typically arise by the time mice reach 9 months of age. The sensory function (such as taste, smell, hearing, and vision) starts to deteriorate when amyloid peptide buildups and neuroinflammation spread into related anatomical structures. The cognitive functions, encompassing learning and memory abilities, such as visual recognition, associative, spatial working, reference learning, and memory show signs of decline from 4 to 6 months of age. Concerning neuropsychiatric-like symptoms, comprising apathy, anxiety and depression, and the willingness for exploratory behaviour, it is believed that motivational changes emerge by approximately 6 months of age. Unfortunately, numerous studies from different laboratories are often contradictory on the conclusions drawn and the identification of onset age, making preclinical studies in rodent models not easily translatable to humans. This variability is likely due to a range of factors associated with animals themselves, housing and husbandry conditions, and experimental settings. In the forthcoming studies, greater clarity in experimental details when conducting behavioural testing in 5xFAD transgenic mice could minimise the inconsistencies and could ensure the reliability and the reproducibility of the results. Full article

In the present study, we conducted a scoping review to provide an overview of the existing literature on the carbocyanine dye DiI, in human neuroanatomical tract tracing. The PubMed, Scopus, and Web of Science databases were systematically searched. We identified 61 studies published during the last three decades. While studies incorporated specimens across human life from the embryonic stage onwards, the majority of studies focused on adult human tissue. Studies that utilized peripheral nervous system (PNS) tissue were a minority, with the majority of studies focusing on the central nervous system (CNS). The most common topic of interest in previous tract tracing investigations was the connectivity of the visual pathway. DiI crystals were more commonly applied. Nevertheless, several studies utilized DiI in a paste or dissolved form. The maximum tracing distance and tracing speed achieved was, respectively, 70 mm and 1 mm/h. We identified studies that focused on optimizing tracing efficacy by varying parameters such as fixation, incubation temperature, dye re-application, or the application of electric fields. Additional studies aimed at broadening the scope of DiI use by assessing the utility of archival tissue and compatibility of tissue clearing in DiI applications. A combination of DiI tracing and immunohistochemistry in double-labeling studies have been shown to provide the means for assessing connectivity of phenotypically defined human CNS and PNS neuronal populations. Full article

EEG, which can provide brain alteration information via recording the electrical activity of neurons in the cerebral cortex, has been widely used in neurophysiology. However, conventional wet electrodes in EEG monitoring typically suffer from inherent limitations, including the requirement of skin pretreatment, the risk of superficial skin infections, and signal performance deterioration that may occur over time due to the air drying of the conductive gel. Although the emergence of dry electrodes has overcome these shortcomings, their electrode–skin contact impedance is significantly high and unstable, especially in hair-covered areas. To address the above problems, an active claw-shaped dry electrode is designed, moving from electrode morphological design, slurry preparation, and coating to active electrode circuit design. The active claw-shaped dry electrode, which consists of a claw-shaped electrode and active electrode circuit, is dedicated to offering a flexible solution for elevating electrode fittings on the scalp in hair-covered areas, reducing electrode–skin contact impedance and thus improving the quality of the acquired EEG signal. The performance of the proposed electrodes was verified by impedance, active electrode circuit, eyes open-closed, steady-state visually evoked potential (SSVEP), and anti-interference tests, based on EEG signal acquisition. Experimental results show that the proposed claw-shaped electrodes (without active circuit) can offer a better fit between the scalp and electrodes, with a low electrode–skin contact impedance (18.62 KΩ@1 Hz in the hairless region and 122.15 KΩ@1 Hz in the hair-covered region). In addition, with the active circuit, the signal-to-noise ratio (SNR) of the acquiring EEG signal was improved and power frequency interference was restrained, therefore, the proposed electrodes can yield an EEG signal quality comparable to wet electrodes. Full article

We present novel workflows for Q-FISH nanoscopy with the potential for prognostic applications and resolving novel chromatin compaction changes. DNA-fluorescence in situ hybridization (DNA-FISH) is a routine application to visualize telomeres, repetitive terminal DNA sequences, in cells and tissues. Telomere attrition is associated with inherited and acquired diseases, including cancer and cardiomyopathies, and is frequently analyzed by quantitative (Q)-FISH microscopy. Recently, nanoscopic imaging techniques have resolved individual telomere dimensions and their compaction as a prognostic marker, in part leading to conflicting conclusions still unresolved to date. Here, we developed a comprehensive Q-FISH nanoscopy workflow to assess telomeres with PNA telomere probes and 3D-Stimulated Emission Depletion (STED) microscopy combined with Dynamic Intensity Minimum (DyMIN) scanning. We achieved single-telomere resolution at high, unprecedented telomere coverage. Importantly, our approach revealed a decrease in telomere signal density during mitotic cell division compared to interphase. Innovatively expanding FISH-STED applications, we conducted double FISH targeting of both telomere- and chromosome-specific sub-telomeric regions and accomplished FISH-STED in human cardiac biopsies. In summary, this work further advanced Q-FISH nanoscopy, detected a new aspect of telomere compaction related to the cell cycle, and laid the groundwork for future applications in complex cell types such as post-mitotic neurons and muscle cells. Full article