Nerve Impulses Research Articles

Simulations of nerve signal propagation in axons

PurposeIn the literature, soliton solutions of the Heimburg–Jackson model have been proposed by Drab et al. (2022), but for the considered models, i.e. Eq.(1) and Eq.(2), the existence of solitons, the dispersion analysis and the pseudospectral method have been studied (Engelbrecht et al., 2006, 2018, 2020; Tamm et al., 2017, 2022; Peets et al., 2013). Therefore, the gap should be filled by this work.Design/methodology/approachWhen nonlinear terms, dissipative terms and forcing terms are ignored, the system (Eq.(2)) reduces to a single, sixth-order partial differential equation (Tamm et al., 2022). In this work, our aim is to propose analytical solutions in the explicit form via ansatz-based method. Therefore, the parameter effects in wave profile will be proposed clearly in figures.FindingsWhile progress has been made in signal propagation in nerves, thanks to many experimental studies and theoretical predictions over the last two centuries, the results obtained in this study may answer new questions that arise.Originality/valueIn the literature, the existence of solitons, dispersion analysis and pseudospectral method have been investigated for the Heimburg-Jackson model (Engelbrecht et al., 2006, 2018, 2020; Tamm et al., 2017, 2022; Peets et al., 2013), and this study fills the gap in soliton solutions. Additionally, when nonlinear terms, dissipative term and forcing terms are ignored, the system (Eq.(2)) reduced to a single equation that is sixth-order partial differential equation (Tamm et al., 2022). In this work, our aim is to propose analytical solutions in the explicit form via ansatz-based method. Therefore, the parameter effects in wave profile will be proposed clearly in figures.

Establishment of a Serum-Free Human iPSC-Derived Model of Peripheral Myelination.

Myelination and the formation of nodes of Ranvier are essential for the rapid conduction of nerve impulses along axons in the peripheral nervous system (PNS). While many animal-based and serum-containing models of peripheral myelination have been developed, these have limited ability when it comes to studying genetic disorders affecting peripheral myelination. We report a fully induced pluripotent stem cell (iPSC)-derived human model of peripheral myelination using Schwann cells (SCs) and motoneurons, cultured in a serum-free medium on patterned and nonpatterned surfaces. Results demonstrated iPSC-derived SC-expressed early growth response protein 2 (Egr2), a key transcription factor for myelination, and after ∼30 days in coculture, hallmark features of myelination, including myelin segment and node of Ranvier formation, were observed. Myelin segments were stained for the myelin basic protein, which surrounded neurofilament-stained motoneuron axons. Clusters of voltage-gated sodium channels flanked by paranodal protein contactin-associated protein 1, indicating node of Ranvier formation, were also observed. High-resolution confocal microscopy allowed for 3D reconstruction and measurement of myelin g-ratios of myelin segments, with an average g-ratio of 0.67, consistent with reported values in the literature, indicating mature myelin segment formation. This iPSC-based model of peripheral myelination provides a platform to investigate numerous PNS diseases, including Charcot-Marie Tooth disorder, Guillian-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and antimyelin-associated glycoprotein peripheral neuropathy, with the potential for greater translatability to humans for improving the applicability for drug-screening programs.

Influence of Anesthesiology Protocol on the Quality of Intraoperative Nerve Monitoring During Thyroid Surgery, One-Year Single Center Experience

Background/Objectives: Anesthesia plays a very important role in the successful management of intraoperative neuromonitoring (IONM). The aim of our study was to investigate the impact of anesthesia induction and maintenance on the quality of signals during surgeries on the thyroid and parathyroid glands using neuromonitoring. Methods: The study included 72 patients who underwent surgery with IONM for one year. All the patients were intubated using a Glidescope videolaryngoscope with a hyperangulated blade. Two different approaches were used to facilitate intubation: succinylcholine-1 mg/kg and rocuronium bromide-0.3 mg/kg. For anesthesia maintenance, total intravenous anesthesia (TIVA) or combined anesthesia was used. Patients’ body movements during operations, as well as electromyography signals from the vagus and recurrent laryngeal nerves before resection, were recorded as V1 and R1. Results: Intraoperative unwanted movements were recorded in 25% of patients. Undesired movements were more frequently recorded in the TIVA group compared to the combined anesthesia group (p < 0.001) as well as in patients who received succinylcholine compared to patients who received rocuronium bromide (p = 0.028). Type of anesthesia maintenance as well as type of muscle relaxant did not affect the quality of recorded nerve signals. (p = 0.169 and p = 0.894, respectively). Conclusions: The type of muscle relaxant used significantly affects the occurrence of undesirable movements during thyroid surgery with IONM, while the type of anesthesia maintenance did not influence either the quality of the obtained signal or the occurrence of undesirable movements.

SPECIFICS OF PHYSICAL REHABILITATION OF CHILDREN WITH CEREBRAL PALSY

Cerebral palsy (CP) is an umbrella term that covers a group of diseases that manifest themselves mainly in impaired movement, balance and posture. The number of children affected by this disease is constantly growing around the world. Today, cerebral palsy is one of the most common forms of childhood disability, affecting approximately 2-3 children per 1000 births. Purpose. to analyse and systematise the specifics of physical rehabilitation of children with cerebral palsy. Materials and methods. To achieve the objectives of the study, the researchers analysed scientific literature and systematised information using electronic databases such as PubMed, Google Scholar and others. Research results. The main approaches and methods of physical rehabilitation for children with cerebral palsy are traditional physiotherapy, hydrotherapy, botulinum therapy, robotic systems and therapy using virtual reality technologies. The main aspects of physiotherapy are assessment and planning, improving mobility and correcting posture, rehabilitation after surgery, and involvement in everyday life. Hydrotherapy uses the therapeutic properties of water to improve the physical functions and general well-being of children with this disease. The methods of hydrotherapy include swimming, exercises in a hydromassage pool, therapeutic exercises in water, and physiotherapy techniques. Botulinum toxin therapy (BT) is a spasticity treatment with the highest level of scientific evidence, which has been used for ~30 years in patients with cerebral palsy (CP). Botulinum toxin type A is used during botulinum therapy, which is a neurotoxin that blocks the transmission of nerve impulses to the muscles. This leads to a temporary weakening of the muscles, which helps to reduce spasticity and alleviate symptoms. Robotic systems and virtual reality (VR) technologies are innovative approaches used to rehabilitate children with cerebral palsy (CP). These technologies offer new opportunities to improve physical function and quality of life for children. Conclusions. Among a large number of traditional methods of physiotherapy, scientists highlight the high efficiency of Bobath therapy in the physical rehabilitation of children with cerebral palsy. This is also confirmed by the research of Vitalia Kashuba and Bozhena Bukhovets, who developed a physical rehabilitation programme that included Bobath therapy. Hydrotherapy, or water therapy, is an important part of the rehabilitation of children with cerebral palsy. It uses the healing properties of water to improve the physical functions and overall well-being of children with this disease. Research by Aikaterini Bayraktariadou, Konstantinos Chandolias and others demonstrates that hydrotherapy, either as an individual treatment or in combination with a standard exercise programme on land, can significantly contribute to improved mobility, increased exercise endurance and a better quality of life. Botulinum toxin is widely used in the rehabilitation of children with cerebral palsy. A study by Farid Hareb and others shows that botulinum toxin therapy can be an effective method for improving the quality of life of children with cerebral palsy, helping to reduce spasticity and improve their motor function. Also, robotic technologies and VR have recently been actively introduced into the physical rehabilitation of children with cerebral palsy. Research by Hyun Cho Chang, Menekseoglu Ahmet Kivanc, and Rocio Llamas-Ramos confirms the feasibility of combining traditional physiotherapy with robotic systems and virtual reality.

Microenvironment‐Responsive Injectable Conductive Hydrogel for Spinal Cord Injury Repair

AbstractSpinal cord injury (SCI) represents a severe neurological condition often coupled with a drastic secondary inflammatory response, which further exacerbates the damage in most cases. Due to their unique electrical and mechanical compatibilities with the spinal cord, the utilization of conductive hydrogels through injection for SCI repair, particularly in scenarios involving non‐uniform and large gaps, has emerged as a promising approach. Herein, leveraging the acidic microenvironment characteristic of acute SCI sites, an injectable conductive hydrogel with pH‐responsive immunoregulation is engineered for SCI repair. Based on the dynamic Schiff base chemistry and covalent photo‐crosslinking, this composite hydrogel, composed of gelatin methacryloyl, oxidized dextran, and MoS2, exhibits adjustable mechanical and conductive properties, enabling a customized match with the natural spinal cord's attributes. Additionally, the incorporation of Wnt5a and its selective release in acidic conditions prompt the immediate suppression of inflammatory factors and enhances neural differentiation and regeneration. In the 2‐mm hemisection mouse SCI model, the optimized conductive hydrogel can effectively bridge the injury gap, establish nerve connections and signal, mitigate inflammatory response, and promoted recovery of mobility. This novel injectable conductive hydrogel system offers a promising advance in therapeutic materials for SCI repair.

Thumbtack needle at front-mu points for abnormal behavior in children with autism spectrum disorders

To compare the clinical effect of thumbtack needle at front-mu points combined with conventional rehabilitation training and simple conventional rehabilitation training in the treatment of autism spectrum disorders (ASD). A total of 40 children with ASD were randomly divided into a combination group (20 cases, 3 cases dropped out) and a conventional rehabilitation group (20 cases, 3 cases dropped out). Conventional rehabilitation training i.e. language-cognition training and comprehensive education training was adopted in the conventional rehabilitation group, once a day, 5 days a week. On the basis of the treatment in the conventional rehabilitation group, thumbtack needle was applied at Zhongwan (CV 12), bilateral Tianshu (ST 25) and Guanyuan (CV 4) in the combination group, the needles were retained for 3 days each time, 3-day interval was taken between each treatment, for 5 times per month. One-month treatment was as one course and a total of 3 courses were required in both groups, with 10-day break between each course. Before and after treatment, the scores of autism behavior checklist (ABC), childhood autism rating scale (CARS), TCM spleen-stomach symptoms and Achenbach child behavior checklist (CBCL) were observed, and the serum ratio of glutamate and gamma-aminobutyric acid (Glu/GABA) was measured. After treatment, the scores of ABC, CARS and CBCL were decreased compared with those before treatment (P<0.05, P<0.01) in both groups, the TCM spleen-stomach symptoms score was decreased compared with that before treatment (P<0.05) in the combination group; the changes in the scores of ABC, CARS, TCM spleen-stomach symptoms and CBCL, as well as the serum Glu/GABA in the combination group were lager than those in the conventional rehabilitation group (P<0.05, P<0.01). Both thumbtack needle at front-mu points combined with conventional rehabilitation training and simple conventional rehabilitation training can effectively treat ASD, the combination treatment has superior effect on improving the abnormal behavior, spleen-stomach symptoms and balance of nerve impulse and inhibition.

Acute Hypobaric Hypoxia Causes Alterations in Acetylcholine-Mediated Signaling Through Varying Expression of Muscarinic Receptors in the Prefrontal Cortex and Cerebellum of Rats' Brain.

Sharma, Narendra Kumar, Mansi Srivastava, Tikam Chand Dakal, Vipin Ranga, and Pawan Kumar Maurya. Acute hypobaric hypoxia (HH) causes alterations in acetylcholine-mediated signaling through varying expression of muscarinic receptors in the PFC and cerebellum of rats' brain. High Alt Med Biol. 00:00-00, 2024. Background: Muscarinic receptor (CHRM) proteins are G-protein-associated acetylcholine receptors found in neuronal membranes. Five major subtypes, CHRM1-CHRM5, modulate acetylcholine in central nervous system signaling cascades. CHRM1, CHRM3, and CHRM5 are linked to Gαq/Gα11 proteins, whereas CHRM2 and CHRM4 are linked to Gαi/Gαo proteins. Objective: Limited research has been conducted to explore the impact of HH on CHRM gene expressions. It is caused by low oxygen availability at high altitudes, which impairs neurotransmission, cognitive performance, and physiological functions. Previous studies have shown that exposure to hypoxia leads to a reduction in CHRM receptors, which in turn causes alteration in signal transduction, physiological responses, cognitive deficits, and mood alterations. Method: In the present study, we have used semiquantitative PCR to measure muscarinic receptor gene expression after 6, 12, and 24 hours of HH exposure at 25,000 feet using a decompression chamber in rat brain's PFC and cerebellum. Result: We have found that CHRM1-CHRM5 downregulated after acute exposure to hypoxia until 12 hours, and then, the expression level of these receptors increased to 24 hours when compared with 12 hours in PFC. All subtypes have shown a similar pattern in PFC regions under hypoxia exposure. On the other hand, these receptors have shown altered expression at different time points in the cerebellum. CHRM1 and CHRM4 acutely downregulated, CHRM2 and CHRM5 downregulated, while CHRM3 upregulated after hypoxia exposure. Conclusion: Our study, for the first time, has shown the altered expressions of muscarinic receptors under temporal hypoxia exposure. The altered expression pattern has shown an association with acclimatization and protection against necrosis due to hypoxia. This study may pave further investigations for understanding and addressing the cognitive, behavioral, and physiological impacts of hypoxia and therapeutic development.

Transgenic zebrafish as a model for investigating diabetic peripheral neuropathy: investigation of the role of insulin signaling.

Diabetic peripheral neuropathy (DPN), a complication of diabetes mellitus (DM), is a neurodegenerative disorder that results from hyperglycemic damage and deficient insulin receptor (IR) signaling in peripheral nerves, triggered by failure of insulin production and insulin resistance. IR signaling plays an important role in nutrient metabolism and synaptic formation and maintenance in peripheral neurons. Although several animal models of DPN have been developed to identify new drug candidates using cytotoxic reagents, nutrient-rich diets, and genetic manipulations, a model showing beneficial effects remains to be established. In this study, we aimed to develop a DPN animal model using zebrafish to validate the effects of drug candidates on sensory neuropathy through in vivo imaging during the early larval stage. To achieve this, we generated Tg (ins:gal4p16);Tg (5uas:epNTR-p2a-mcherry) zebrafish using an enhanced potency nitroreductase (epNTR)-mediated chemogenetic ablation system, which showed highly efficient ablation of pancreatic β-cells following treatment with low-dose metronidazole (MTZ). Using in vivo live imaging, we observed that sensory nerve endings and postsynaptic formation in the peripheral lateral line (PLL) were defective, followed by a disturbance in rheotaxis behavior without any locomotory behavioral changes. Despite defects in sensory nerves and elevated glucose levels, both reactive oxygen species (ROS) levels, a primary cause of DPN, and the number of ganglion cells, remained normal. Furthermore, we found that the activity of mTOR, a downstream target of IR signaling, was decreased in the PLL ganglion cells of the transgenic zebrafish. Our data indicates that peripheral neuropathy results from the loss of IR signaling due to insulin deficiency rather than hyperglycemia alone.

Rita Levi-Montalcini: From Persecution to the Nobel Prize and an Honorary Degree From a Canadian University.

Rita Levi-Montalcini (RLM) is recognized as a prestigious and renowned researcher of her time. She was the fourth woman to earn the Nobel Prize in Physiology and Medicine in 1986 for the discovery of nerve growth factor (NGF). We review her biography and scientific discovery, and provide an example of why her discovery is still important. She had a special relationship with McGill University, Canada, which we describe. We searched for articles and books about her for biographical and scientific material and met with Dr. Claudio Cuello, Former Chair of McGill's Faculty of Medicine. RLM was born in 1909 in Turin, Italy, where she had studied medicine. She started her career in research. Because of the anti-Jewish racial laws in Italy in 1938, she went underground and continued her projects in her bedroom. After the war, she visited St. Louis, USA, and conducted research there. Her experiments confirmed that tumors release a factor that causes nerve growth and cancer proliferation. Initially, scientists responded to this discovery with skepticism, but after its purification in 1959 and determination of its protein structure in 1971, NGF became widely accepted.Currently, crosstalk between cancers and nerves is poorly understood. The example of prostate cancer shows that surgical or chemical denervation of sympathetic nerves prevents the initiation of prostate tumors, whereas inhibition of parasympathetic nerve signaling reduces the spread of prostate cancer. McGill University awarded RLMa doctoral degree in 2011. It was the first time in itshistory that the University awarded an honorary doctorate outside of Canada, and the second one outside of Quebec.Through her discovery of NGF, RLM exemplified the power of passion and determination despite the obstacles she faced. Her relentless dedication has led to remarkable achievements.

Cajal's contributions to vestibular research.

The Spanish neurohistologist Santiago Ramón y Cajal (1852-1934) is widely regarded as the father of modern Neuroscience. In addition to identifying the individuality of cells in the nervous system (the neuron theory) or the direction followed by nerve impulses (the principle of dynamic polarization), he described numerous details regarding the organization of the different structures of the nervous system. This task was compiled in his magnum opus, "Textura del Sistema Nervioso del Hombre y los Vertebrados," first published in Spanish between 1899 and 1904, and later revised and updated in French as "Histologie du système nerveux de l'homme et des vertébrés" between 1909 and 1911 for wider distribution among the international scientific community. Some of Cajal's findings are fundamental to our understanding of the anatomy and histology of the vestibular system. He depicted the nerve endings in the sensory epithelia, the structure of the vestibular nerve and Scarpa ganglion, afferent vestibular fibers, vestibular nuclei, lateral vestibulospinal tract, vestibulocerebellar connections, and the fine structure of the cerebellum. However, most of these pioneering descriptions were published years earlier in Spanish journals with limited circulation. Our study aimed to gather Cajal's findings on the vestibular system and identify his original publications. After this endeavor, we claim a place for Cajal among the founders of anatomy and histology of the vestibular system.

Exploring the role of Yuxuebi tablet in neuropathic pain with the method of similarity research of drug pharmacological effects based on unsupervised machine learning.

Having multiple pharmacological effects is a characteristic of Traditional Chinese Medicine (TCM). Currently, there is a lack of suitable methods to explore and discover modern diseases suitable for TCM treatment using this characteristic. Unsupervised machine learning technology is an efficient strategy to predict the pharmacological activity of drugs. This study takes Yuxuebi Tablet (YXB) as the research object. Using the unsupervised machine learning technology of drug cell functional fingerprint similarity research, the potential pharmacological effects of YXB were discovered and verified. LC-MS combined with the in vitro intestinal absorption method was used to identify components of YXB that could be absorbed by the intestinal tract of rats. Unsupervised learning hierarchical clustering was used to calculate the degree of similarity of cellular functional fingerprints between these components and 121 marketed Western drugs whose indications are diseases and symptoms that YXB is commonly used to treat. Then, based on the Library of Integrated Network-based Cellular Signatures database, pathway analysis was performed for selected Western drugs with high similarity in cellular functional fingerprints with the components of YXB to discover the potential pharmacological effects of YXB, which were validated by animal experiments. We identified 40 intestinally absorbed components of YXB. Through predictive studies, we found that they have pharmacological effects very similar to non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. In addition, we found that they have very similar pharmacological effects to anti-neuropathic pain medications (such as gabapentin, duloxetine, and pethidine) and may inhibit the NF-κB signaling pathway and biological processes related to pain perception. Therefore, YXB may have an antinociceptive effect on neuropathic pain. Finally, we demonstrated that YXB significantly reduced neuropathic pain in a rat model of sciatic nerve chronic constriction injury (CCI). Transcriptome analysis further revealed that YXB regulates the expression of multiple genes involved in nerve injury repair, signal transduction, ion channels, and inflammatory response, with key regulatory targets including Sgk1, Sst, Isl1, and Shh. This study successfully identified and confirmed the previously unknown pharmacological activity of YXB against neuropathic pain through unsupervised learning prediction and experimental verification.

PHYSIOLOGICAL ASPECT OF AALOCHAK PITTA PERSPECTIVE OF THE MODERN ERA

Ayurvedic science is based on Dosha, Dhatu, and Mala Vijnana. The body's origin and maintenance depend upon the three primary and fundamental units or principles: Doshas Vata, Pitta, and Kapha. The first Aacharya to categorise Pitta Dosha into five categories was Sushruta. Rupa grahana, or the perception of vision, is attributed to the Pitta known as Alochaka Pitta, located in the retina (Drishti). Acharya Bhela has divided this Alochaka Pitta into two categories: intellectually (Buddhi) and visually or optically (Chakshu’s) differentiative. An example of an optically differentiative Pitta creates a differentiation by placing a picture. The visual process, also known as the physiology of vision, is the mechanism by which the outside world is perceived. Specialised cells called photoreceptors start the process that turns light rays into nerve impulses. There are two categories of photoreceptors: Rodes and cones.

The Possible Involvement of Glucagon-like Peptide-2 in the Regulation of Food Intake through the Gut-Brain Axis.

Food intake regulation is a complex mechanism involving the interaction between central and peripheral structures. Among the latter, the gastrointestinal tract represents one of the main sources of both nervous and hormonal signals, which reach the central nervous system that integrates them and sends the resulting information downstream to effector organs involved in energy homeostasis. Gut hormones released by nutrient-sensing enteroendocrine cells can send signals to central structures involved in the regulation of food intake through more than one mechanism. One of these is through the modulation of gastric motor phenomena known to be a source of peripheral satiety signals. In the present review, our attention will be focused on the ability of the glucagon-like peptide 2 (GLP-2) hormone to modulate gastrointestinal motor activity and discuss how its effects could be related to peripheral satiety signals generated in the stomach and involved in the regulation of food intake through the gut-brain axis. A better understanding of the possible role of GLP-2 in regulating food intake through the gut-brain axis could represent a starting point for the development of new strategies to treat some pathological conditions, such as obesity.

Maid gene dysfunction promotes hyperobesity via the reduction of adipose tissue inflammation in Mc4r gene-deficient mice

The onset and progression mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are being studied. We developed and analyzed a new mouse model of obesity by combining maternal Id-like molecule (Maid) and melanocortin-4 receptor (Mc4r) gene deletions. Four mice, each at 12 and 28 weeks of age, were analyzed for each genotype: Maid gene knockout, Mc4r gene knockout, combined Mc4r and Maid gene knockout, and Mc4r gene knockout with a high-fat diet. Mice with a combined deficiency of Mc4r and Maid gene showed significantly more severe obesity compared to all other genotypes, but no liver fibrosis or a decline in metabolic status were observed. In visceral white adipose tissue, Maid and Mc4r gene knockout mice had fewer CD11c-positive cells and lower mRNA expression of both inflammatory and anti-inflammatory cytokines. Furthermore, Maid and Mc4r gene knockout mice showed lower expression of adipocytokines in visceral white adipose tissue and uncoupling protein-1 in scapular brown adipose tissue. The expression of adipocytokines and uncoupling protein-1 is regulated by sympathetic nerve signaling that contribute severe obesity in Maid and Mc4r gene knockout mice. These mechanisms contribute hyperobesity in Maid and Mc4r gene knockout mice.

Environmental Temperature Variation Affects Brain Lipid Composition in Adult Zebrafish (Danio rerio).

This study delves deeper into the impact of environmental temperature variations on the nervous system in teleost fish. Previous research has demonstrated that exposing adult zebrafish (Danio rerio) to 18 °C and 34 °C for 4 or 21 days induces behavioural changes compared to fish kept at a control temperature of 26 °C, suggesting alterations in the nervous system. Subsequent studies revealed that these temperature conditions also modify brain protein expression, indicating potential neurotoxic effects. The primary aim of this work was to investigate the effects of prolonged exposure (21 days) to 18 °C or 34 °C on the brain lipidomes of adult zebrafish compared to a control temperature. Analysis of the brain lipidome highlighted significant alteration in the relative abundances of specific lipid molecules at 18 °C and 34 °C, confirming distinct effects induced by both tested temperatures. Exposure to 18 °C resulted in an increase in levels of phospholipids, such as phosphatidylethanolamine, alongside a general reduction in levels of sphingolipids, including sphingomyelin. Conversely, exposure to 34 °C produced more pronounced effects, with increases in levels of phosphatidylethanolamine and those of various sphingolipids such as ceramide, gangliosides, and sphingomyelin, alongside a reduction in levels of ether phospholipids, including lysophosphatidylethanolamine ether, phosphatidylethanolamine ether, and phosphatidylglycerol ether, as well as levels of glycolipids like monogalactosyldiacylglycerol. These results, when integrated with existing proteomic and behavioural data, offer new insights into the effects of thermal variations on the nervous system in teleost fish. Specifically, our proteomic and lipidomic findings suggest that elevated temperatures may disrupt mitochondrial function, increase neuronal susceptibility to oxidative stress and cytotoxicity, alter axonal myelination, impair nerve impulse transmission, hinder synapse function and neurotransmitter release, and potentially lead to increased neuronal death. These findings are particularly relevant in the fields of cell biology, neurobiology, and ecotoxicology, especially in the context of global warming.

Potential brain biomarkers in patients with Autism spectrum syndrome

Autism spectrum disorder (ASD) is referred as a cluster of neurodevelopmental disorders with relatively high incidence. ASD is believed to be a multifactorial condition, and genetics is one of the most important factors in its formation. Therefore, profiling gene expression in ASD patients can lead to the identification of new molecular insights. To evaluate gene expression patterns, we have utilized NCBI GEO microarray data. The dataset of ASD patients (GSE28475, GSE28521, GSE38322 and GSE113834) were defined as two meta-data, Total brain meta-data and Lobe specified meta-data. Meta-analysis and batch effect removal was conducted by the SVA package. Microarray data analysis was performed using the LIMMA package under R 4.2.1 software. Total Meta-Analysis (TMA) identified 525 significantly differentially expressed genes (DEGs) in ASD patient’s brain. The temporal and frontal lobes of ASD patients showed 96 and 23 DEGs respectively. Among the mentioned DEGs, there were 11 common DEGs between the temporal and frontal lobes that were also dysregulated in TMA except for UTP4 which was only dysregulated in the temporal and frontal lobes. However, the occipital and cerebellum lobes did not show any significant DEGs. Enrichment analysis pointed out the vital roles of identified DEGs in transmembrane transportation, ATP production, and cellular respiration. According to our findings, gene expression profile in the temporal and frontal lobes of ASD patients are significantly different than a control group. This aberrant gene expression potentially leads to crucial complications in nerve signal transmission and defects energy production in neurons. Therefore, potential therapeutic targets may be suggested based on these findings.

Inhibition of inflammatory osteoclasts accelerates callus remodeling in osteoporotic fractures by enhancing CGRP+TrkA+ signaling.

Impaired callus remodeling significantly contributes to the delayed healing of osteoporotic fractures; however, the underlying mechanisms remain unclear. Sensory neuronal signaling plays a crucial role in bone repair. In this study, we aimed to investigate the pathological mechanisms hindering bone remodeling in osteoporotic fractures, particularly focusing on the role of sensory neuronal signaling. We demonstrate that in ovariectomized (OVX) mice, the loss of CGRP+TrkA+ sensory neuronal signaling during callus remodeling correlates with increased Cx3cr1+iOCs expression within the bone callus. Conditional knockout of Cx3cr1+iOCs restored CGRP+TrkA+ sensory neuronal, enabling normal callus remodeling progression. Mechanistically, we further demonstrate that Cx3cr1+iOCs secrete Sema3A in the osteoporotic fracture repair microenvironment, inhibiting CGRP+TrkA+ sensory neurons' axonal regeneration and suppressing nerve-bone signaling exchange, thus hindering bone remodeling. Lastly, in human samples, we observed an association between the loss of CGRP+TrkA+ sensory neuronal signaling and increased expression of Cx3cr1+iOCs. In conclusion, enhancing CGRP+TrkA+ sensory nerve signaling by inhibiting Cx3cr1+iOCs activity presents a potential strategy for treating delayed healing in osteoporotic fractures. Inhibition of inflammatory osteoclasts enhances CGRP+TrkA+ signaling and accelerates callus remodeling in osteoporotic fractures.

Microalgal biofilm induces larval settlement in the model marine worm Platynereis dumerilii.

A free-swimming larval stage features in many marine invertebrate life cycles. To transition to a seafloor-dwelling juvenile stage, larvae need to settle out of the plankton, guided by specific environmental cues that lead them to an ideal habitat for their future life on the seafloor. Although the marine annelid Platynereis dumerilii has been cultured in research laboratories since the 1950s and has a free-swimming larval stage, specific environmental cues that induce settlement in this nereid worm are yet to be identified. Here, we demonstrate that microalgal biofilm is a key settlement cue for P. dumerilii larvae, inducing earlier onset of settlement and enhancing subsequent juvenile growth as a primary food source. We tested the settlement response of P. dumerilii to 40 different strains of microalgae, predominantly diatom species, finding that P. dumerilii have species-specific preferences in their choice of settlement substrate. The most effective diatom species for inducing P. dumerilii larval settlement were benthic pennate species including Grammatophora marina, Achnanthes brevipes and Nitzschia ovalis. The identification of specific environmental cues for P. dumerilii settlement enables a link between its ecology and the sensory and nervous system signalling that regulates larval behaviour and development. Incorporation of diatoms into P. dumerilii culture practices will improve the husbandry of this marine invertebrate model.

Ultraconformable cuff implants for long-term bidirectional interfacing of peripheral nerves at sub-nerve resolutions

Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices record nerve action potentials with fascicle-specific resolution and extract from these the conduction velocity and direction of propagation. The cuffs exhibit high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices are able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. When used in a partial nerve ligation rodent model, the cuffs identify and characterise changes in nerve C fibre activity associated with the development of neuropathic pain in freely-moving animals. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.

Canavan disease: a rare case report

Canavan disease is a very rare, fatal, autosomal recessive neurodegenerative disorder. It usually manifests during infancy. Mutations in the aspartoacylase (ASPA) gene (17p13.3), which code for the aspartoacylase enzyme, cause this disease. It is a leukodystrophy and affects white matter of the brain. This disease is associated with deficiency of an essential enzyme, aspartoacylase. The deficiency leads to loss of white matter in brain, leading to defective transmission of nerve signals. This disorder affects all ethnic groups, but occurs with greater frequency, in individuals of Ashkenazi Jewish descent.