Neural Cells Research Articles

Construction of a Prognostic Model for Mitochondria and Macrophage Polarization Correlation in Glioma Based on Single-Cell and Transcriptome Sequencing.

Numerous diseases are associated with the interplay of mitochondrial and macrophage polarization. However, the correlation of mitochondria-related genes (MRGs) and macrophage polarization-related genes (MPRGs) with the prognosis of glioma remains unclear. This study aimed to examine this relationship based on bioinformatic analysis. Glioma-related datasets (TCGA-GBMLGG, mRNA-seq-325, mRNA-seq-693, GSE16011, GSE4290, and GSE138794) were included in this study. The intersection genes were obtained by overlapping differentially expressed genes (DEGs) from differential expression analysis in GSE16011, key module genes from WGCNA, and MRGs. Subsequently, the intersection genes were further screened to obtain prognostic genes. Following this, a risk model was developed and verified. After that, independent prognostic factors were identified, followed by the construction of a nomogram and subsequent evaluation of its predictive ability. Furthermore, immune microenvironment analysis and expression validation were implemented. The GSE138794 dataset was utilized to evaluate the expression of prognostic genes at a cellular level, followed by conducting an analysis on cell-to-cell communication. Finally, the results were validated in different datasets and tissue samples from patients. ECI2, MCCC2, OXCT1, SUCLG2, and CPT2 were identified as prognostic genes for glioma. The risk model constructed based on these genes in TCGA-GBMLGG demonstrated certain accuracy in predicting the occurrence of glioma. Additionally, the nomogram constructed based on risk score and grade exhibited strong performance in predicting patient survival. Significant differences were observed in the proportion of 27 immune cell types (e.g., activated B cells and macrophages) and the expression of 32 immune checkpoints (e.g., CD70, CD200, and CD48) between the two risk groups. Single-cell RNA sequencing showed that CPT2, ECI2, and SUCLG2 were highly expressed in oligodendrocytes, neural progenitor cells, and BMDMs, respectively. The results of cell-cell communication analysis revealed that both oligodendrocytes and BMDMs exhibited a substantial number of interactions with high strength. This study revealed five genes associated with the prognosis of glioma (ECI2, MCCC2, OXCT1, SUCLG2, and CPT2), providing novel insights into individualized treatment and prognosis.

Neurodegenerative Diseases: What Can Be Learned from Toothed Whales?

Neurodegeneration involves a wide range of neuropathological alterations affecting the integrity, physiology, and architecture of neural cells. Many studies have demonstrated neurodegeneration in different animals. In the case of Alzheimer's disease (AD), spontaneous animal models should display two neurohistopathological hallmarks: the deposition of β-amyloid and the arrangement of neurofibrillary tangles. However, no natural animal models that fulfill these conditions have been reported and most research into AD has been performed using transgenic rodents. Recent studies have also demonstrated that toothed whales - homeothermic, long-lived, top predatory marine mammals - show neuropathological signs of AD-like pathology. The neuropathological hallmarks in these cetaceans could help to better understand their endangered health as well as neurodegenerative diseases in humans. This systematic review analyzes all the literature published to date on this trending topic and the proposed causes for neurodegeneration in these iconic marine mammals are approached in the context of One Health/Planetary Health and translational medicine.

Comparison of forced and voluntary exercise types on male rat brain monoamine levels, anxiety-like behaviour, and physiological indexes under light and dark phases

PurposePhysical exercise improves physical and mental health; however, the differences between voluntary and forced exercise protocols are unclear. In addition, knowledge regarding the consequences of differences in testing timing, such as light and dark phases, in response to exercise type is limited. We investigated the effects of chronic forced and voluntary wheel running on the changes in brain monoamine levels (5-HT: serotonin, DA: dopamine, NA: noradrenaline), anxiety-like behaviours, and physiological stress responses in the light and dark phases. MethodsAdult male Wistar rats were equally and randomly assigned to four groups: sedentary control, voluntary exercise (free running on a wheel, V-EX), voluntary limited exercise (wheel available only 1h/day, VL-EX), and forced exercise (running on a motorised wheel, F-EX). Each group was further divided into dark- or light-experimental condition groups. After 4 weeks, the rats underwent an open-field test. The monoamines and their metabolite levels were measured in the major neural cell bodies and the projection areas related to behaviour, cognition, anxiety, and stress in the brain. ResultsAdrenal hypertrophy and elevated body temperature, except during the exercise period, were observed in the F-EX rats that exhibited anxiety-like behaviour. The levels of monoamines and their metabolites, particularly the 5-HTergic and DAergic systems, in specific areas, were significantly altered in the rats in the V-EX group compared to those in the VL-EX and other groups. These differences were observed only in the dark phase. ConclusionThe results suggest that V-EX mainly stimulates the 5-HTergic and DAergic systems, while F-EX induces physiological stress and increases anxiety-like behaviour during the dark phase. This study highlights the importance of accounting for exercise types and light/dark phases in behavioural neuroscience experiments.

Evaluating chemical effects on human neural cells through calcium imaging and deep learning

Evaluating chemical effects on human neural cells through calcium imaging and deep learning

Hepatocellular carcinoma hosts cholinergic neural cells and tumoral hepatocytes harboring targetable muscarinic receptors

Background & aimsUnexplained interpatient variation and treatment failure in HCC prompt for renewed approaches. Hepatic neurons, belonging to the autonomic nervous system (ANS), mediate liver/whole body cross-talks. Pathological innervation of the ANS have been identified in cancer, nurturing tumor stroma and conferring stronger carcinogenic properties. MethodsWe characterized the innervation of liver tumors from the French Liver Biobank, then applied bioinformatics to the TCGA, several other datasets and a European validation cohort, to re-evaluate patient stratification. Cell biology and pharmacology studies were also done. ResultsDensely packed nucleated DCX+, synaptophysin+, NeuN+, VAChT+, TH-, CD31-, CD45- clusters, to date undetected, were identified in human HCCs, and independently confirmed by scRNA-seq data. Using the new concept of neuronal score, human and rat HCCs displayed tightly netrin-1-associated neural reconfiguration towards cholinergic polarity along with CLD progression, cancer onset and many features of aggressive (proliferative class) HCC, including shortened survival. This score was conditioned by tumoral hepatocytes, and predicted sorafenib efficacy in the STORM HCC phase 3 trial. Conversely, intratumoral adrenergic lymphocytes were enriched in TEMRA and cytotoxic phenotypes. Amongst all cholinergic transcripts, the medically-targeted CHRM3 receptor was enriched in HCC and associated with cells’ and tumors’ pathogenic traits, displayed adverse prognostic value by the log-rank test in HCC stages 1-2, while collapsing upon experimental re-differentiation. Its pharmacological inhibition by low concentrations of anticholinergic drugs, but not cholinomimetics, decreased anchorage-independent and anoikis growth, synergized with sorafenib and lenvatinib in HCC class 1 to 3 lines, yet not in primary human hepatocytes, and preserved mature hepatocytic functions. ConclusionThese data identify cholinergic processes as instrumental in liver carcinogenesis, and support the use of EMA/FDA-approved cholinergic drugs in HCC research. Impact and implicationsHCC care has long been hampered by the enigmatic nature of disease evolution, as well as of response or resistance to treatment. Hepatic neurons are likely the least studied liver cell type and mediate patients singularities to the organ in real-time. Cholinergic inputs identified in this study as pathogenic may be targeted with the well charted pharmacopoeia of neurotropic drugs already available, for basic or clinical research purposes, with an expected high level of safety.

Brain single-cell transcriptomics highlights comorbidity-related cell type-specific changes of Parkinson’s disease with major depressive disorder after paraquat exposure

Paraquat (PQ), a commonly used herbicide, is a potent environmental neurotoxin associated with Parkinson’s disease (PD) and major depressive disorder (MDD). While the involvement of various brain cell types in the etiology of each disorder is well recognized, the specific cell subtypes implicated in the comorbidity of PD and MDD, especially under PQ neurotoxicity, remain poorly understood. In this study, we used single-cell RNA sequencing (scRNA-seq) to analyze brain tissues from mice with PQ-induced PD with MDD. By integrating genomic data with scRNA-seq profiles, we identified differences in cellular heterogeneity related to the pathogenesis of PD and MDD under PQ exposure. Our analysis of risk enrichment in genes with cell type-specific expression patterns revealed that astrocytes are predominantly linked to the comorbidity of PQ-induced PD and MDD. Furthermore, we identified a specific astrocyte subtype that plays a major role in the comorbidity-related changes observed in PQ-induced PD and MDD. This subtype appears to interact with and potentially transform into MDD-specific and PD-specific subtypes. Additionally, pathways related to chemical synaptic function and neuro-projection development were involved in all key stages of PD and MDD co-occurrence. We also identified RNF7 and MTCH2 as shared diagnostic hub genes for PD and MDD, which changed significantly in astrocytes following PQ exposure. These genes may serve as potential markers for astrocyte-specific prognostic diagnosis of PQ-induced PD with MDD. In summary, this study provides the first scRNA-seq profile of comorbidity in a PQ-exposed model. It highlights the heterogeneity of astrocytes in comorbidity and elucidates potential mechanisms underlying the co-occurrence of PD and MDD. These findings emphasize the need for further research into the pathogenesis of PD comorbid with MDD and offer novel insights into PQ neurotoxicity.

Retracted] Brain cell apoptosis inhibition by butylphthalide in Alzheimer's disease model in rats.

[This retracts the article DOI: 10.3892/etm.2017.4322.].

Nanoparticle-Based Drug Delivery Systems Enhance Treatment of Cognitive Defects.

Nanoparticle-based drug delivery presents a promising solution in enhancing therapies for neurological diseases, particularly cognitive impairment. These nanoparticles address challenges related to the physicochemical profiles of drugs that hinder their delivery to the central nervous system (CNS). Benefits include improved solubility due to particle size reduction, enhanced drug penetration across the blood-brain barrier (BBB), and sustained release mechanisms suitable for long-term therapy. Successful application of nanoparticle delivery systems requires careful consideration of their characteristics tailored for CNS delivery, encompassing particle size and distribution, surface charge and morphology, loading capacity, and drug release kinetics. Literature review reveals three main types of nanoparticles developed for cognitive function enhancement: polymeric nanoparticles, lipid-based nanoparticles, and metallic or inorganic nanoparticles. Each type and its production methods possess distinct advantages and limitations. Further modifications such as coating agents or ligand conjugation have been explored to enhance their brain cell uptake. Evidence supporting their development shows improved efficacy outcomes, evidenced by enhanced cognitive function assessments, modulation of pro-oxidant markers, and anti-inflammatory activities. Despite these advancements, clinical trials validating the efficacy of nanoparticle systems in treating cognitive defects are lacking. Therefore, these findings underscore the need for researchers to expedite clinical testing to provide robust evidence of the potential of nanoparticle-based drug delivery systems.

Recent Advancements and SAR Studies of Synthetic Coumarins as MAO-B Inhibitors: An Updated Review.

The oxidative deamination of a wide range of endogenous and exogenous amines is catalyzed by a family of enzymes known as monoamine oxidases (MAOs), which are reliant on flavin-adenine dinucleotides. Numerous neurological conditions, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are significantly correlated with changes in the amounts of biogenic amines in the brain caused by MAO. Hydrogen peroxide, reactive oxygen species, and ammonia, among other toxic consequences of this oxidative breakdown, can harm brain cells' mitochondria and cause oxidative damage. The prime objective of this review article was to highlight and conclude the recent advancements in structure-activity relationships of synthetic derivatives of coumarins for MAO-B inhibition, published in the last five years' research articles. The literature (between 2019 and 2023) was searched from platforms like Science Direct, Google Scholar, PubMed, etc. After going through the literature, we have found a number of coumarin derivatives being synthesized by researchers for the inhibition of MAO-B for the management of diseases associated with the enzyme such as Alzheimer's Disease and Parkinson's Disease. The effect of these coumarin derivatives on the enzyme depends on the substitutions associated with the structure. The structure-activity relationships of the synthetic coumarin derivatives that are popular nowadays have been described and summarized in the current study. The results revealed the updated review on SAR studies of synthetic coumarins as MAO-B inhibitors, specifically for Alzheimer's Disease and Parkinson's Disease. The patents reported on coumarin derivatives as MAO-B inhibitors were also highlighted. Recently, coumarins, a large class of chemicals with both natural and synthetic sources, have drawn a lot of attention because of the vast range of biological actions they have that are linked to neurological problems. Numerous studies have demonstrated that chemically produced and naturally occurring coumarin analogs both exhibited strong MAO-B inhibitory action. Coumarins bind to MAO-B reversibly thereby preventing the breakdown of neurotransmitters like dopamine leading to the inhibition of the enzyme A number of MAO-B blockers have been proven to be efficient therapies for treating neurological diseases like Alzheimer's Disease and Parkinson's Disease. To combat these illnesses, there is still an urgent need to find effective treatment compounds.

Microenvironment Self-Adaptive Nanomedicine Promotes Spinal Cord Repair by Suppressing Inflammation Cascade and Neural Apoptosis.

Despite various biomaterial-based strategies are tried in spinal cord injury (SCI), developing safe and effective microinvasive pharmacotherapy strategies is still an unmet clinical need. Stimuli-responsive nanomedicine has emerged as a promising non-invasion technology, which enhances drug delivery and promotes functional recovery following SCI. Considering the multiple progressive pathological events and the blood spinal cord barrier (BSCB) associating SCI, a microenvironment self-adaptive nanoparticle (custom-designed with rabies virus glycoprotein 29-RVG29 and hyaluronic acid-HA, RHNP) capable of consistently crossing the BSCB and selectively targeting inflammatory cells and neural cells based on different stages of SCI are developed. The data indicated that RHNP can effectively traverse the BSCB through RVG29, and adaptively modulate cellular internalization by selectively exposing either HA or RVG29 through diselenide bonds, depending on pathological reactive oxygen species (ROS) signals. Furthermore, curcumin is loaded into RHNP (RHNP-Cur) to improve motor function and coordination of hind-limbs in a traumatic SCI mouse model. This study finds that RHNP-Cur exhibited inhibitory effects on the inflammatory cascade originating from M1 microglia/macrophages and neurotoxic astrocytes, and protected neural cells from inflammation-induced apoptosis during nerve regeneration. Collectively, the work provides a microenvironment self-adaptive nanomedicine which enables efficient microinvasive treatment of SCI.

Features of Brain Damage after Neutron Irradiation of the Head and Modification of the Damage by Lactoferrin.

: Mouse heads were irradiated in a beam of neutrons and gamma rays from the IR-8 nuclear reactor. The brain cells of control and irradiated mice were isolated using Percoll. Neurons and resting and activated microglial cells were analyzed using the fluorescently labeled antibodies and flow cytometry. The level of DNA double-strand breaks in neurons was determined by γH2AX histone content. Cytokine gene expression in the hippocampus was studied by RT-PCR. Behavior and cognitive functions were studied using the open field, Morris water maze, and novel object recognition tests. LF was isolated from female colostrum by preparative ion-exchange chromatography and purified by affinity chromatography on heparin-Sepharose. : γ,n-Irradiation of the mouse head at a dose of 1.5 Gy led to an increase in the level of DNA double-strand breaks in neurons. Twenty-four hours after irradiation the total number of cells and the number of neurons in the isolated fraction of brain cells decreased, but the number of microglial cells remained unchanged. The number of resting and activated microglia did not change within 3-72 h after γ,n-irradiation. The expression level of the TNFα, IL-1β, and IL-6 genes increased 2 months after γ,n-irradiation of the mouse head at a dose of 1.5 Gy, indicating the development of neuroinflammation. At this time, irradiated mice demonstrated the anxiety-like behavior and impaired spatial and episodic memory. A single i.p. administration of human LF to mice immediately after γ,n-irradiation of the head did not affect the observed radiation-induced disturbances, but decreased the gene expression levels of TNFα, IL-1β, and IL-6 pro-inflammatory cytokines and increased the gene expression level of TGFβ anti-inflammatory cytokine in the hippocampus 2 months after radiation exposure. The obtained results indicate a partial decrease in the level of hippocampal neuroinflammation of irradiated animals treated with LF. . γ,n-Irradiation of the mouse head at a dose of 1.5 Gy leads to DNA damage of neurons and the decrease in the number of neurons. Microglia cells are more resistant to such radiation exposure. Late after head-only γ,n-irradiation, mice develop neuroinflammation, which is detected by an increase in the pro-inflammatory cytokine gene expression in the hippocampus and also by anxiety-like behavior and impaired cognitive functions. A single LF administration leads to a partial decrease in the neuroinflammation level, but does not affect the other studied parameters. The optimal dosing regimen of LF remains to be determined to preserve cognitive functions after γ,n-irradiation of the brain.

Potentialities of IGF-1 for regulating oxidative stress in neuroinflammation and neurodegeneration: theoretical review

Insulin-like growth factor-1 (IGF-1) elicits a variety of effects on the regulation of oxidative stress, a topic that remains shrouded in controversy. This intricate regulation plays a pivotal role in the aging process and its associated diseases. Notably, it centers around the challenge posed by endogenous antioxidant defenses, which often struggle to counteract free radicals-induced damage to various neural cell macromolecules. The interplay between IGF-1 and oxidative stress holds significant implications. Both factors are intertwined in the context of degenerative and inflammatory disruptions within the central nervous system (CNS), giving rise to dysfunctions in neurons and glial cells. These dysfunctions encompass detrimental outcomes such as excitotoxicity, neuronal attrition, and axonal impairment, all of which are closely related to behavioral irregularities. However, the complexities of IGF-1’s impact remain a topic of debate. Divergent research findings present IGF-1 as both an antioxidative agent and a catalyst to produce reactive oxygen species (ROS) in various neuropathologies. This diversity of outcomes has contributed to the ongoing controversy in the field. The present theoretical review undertakes a comprehensive vision, shedding light on the role of IGF-1 as a regulator within the mechanistic framework of oxidative stress responses. This regulatory role serves as the basis for the emergence of progressive neurodegenerative and neuroinflammatory conditions. Particularly compelling is the exploration of IGF-1 as a potential target for promising therapeutic interventions in this domain. However, the review also highlights significant limitations, including the considerations to work with this factor and the need for further research to clarify IGF-1’s role. Future perspectives should focus on refining our understanding of IGF-1’s mechanisms and exploring its therapeutic potential in more detail.

SARS-CoV-2 persistence: A potential catalyst for age-associated neurodegenerative diseases

The persistence of RNA viruses in the brain is increasingly recognized as a significant factor in the progression of age-related neurodegenerative diseases. This phenomenon is particularly evident in infections caused by various neurotropic and non-neurotropic viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has underscored the urgent need to explore the complex relationship between viral persistence and neurological decline. Growing evidence indicates that SARS-CoV-2 affects brain structure and function, although the precise molecular mechanisms remain poorly understood. Chronic neuroinflammation induced by viral infections is thought to accelerate age-related neurodegeneration. While the immune system typically clears many viral infections in the brain, some viruses establish chronic infections, leading to restricted viral replication. These persistent infections can exacerbate neuroinflammation and contribute to ongoing neuronal damage, key drivers of age-related neurodegeneration. This review explores current knowledge on how SARS-CoV-2 infiltrates the brain, evades immune defenses, and persists within brain cells, potentially using them as viral reservoirs. As individuals age, the cumulative effects of such viral infections may accelerate cognitive decline and increase vulnerability to neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Understanding the molecular mechanisms of viral persistence and its long-term impact on brain health is crucial for developing targeted therapies to combat these age-related diseases.

Single-cell transcriptomic and proteomic analysis of Parkinson's disease brains.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, and recent evidence suggests that pathogenesis may be in part mediated by inflammatory processes, the molecular and cellular architectures of which are largely unknown. To identify and characterize selectively vulnerable brain cell populations in PD, we performed single-nucleus transcriptomics and unbiased proteomics to profile the prefrontal cortex from postmortem human brains of six individuals with late-stage PD and six age-matched controls. Analysis of nearly 80,000 nuclei led to the identification of eight major brain cell types, including elevated brain-resident T cells in PD, each with distinct transcriptional changes in agreement with the known genetics of PD. By analyzing Lewy body pathology in the same postmortem brain tissues, we found that α-synuclein pathology was inversely correlated with chaperone expression in excitatory neurons. Examining cell-cell interactions, we found a selective abatement of neuron-astrocyte interactions and enhanced neuroinflammation. Proteomic analyses of the same brains identified synaptic proteins in the prefrontal cortex that were preferentially down-regulated in PD. By comparing this single-cell PD dataset with a published analysis of similar brain regions in Alzheimer's disease (AD), we found no common differentially expressed genes in neurons but identified many shared differentially expressed genes in glial cells, suggesting that the disease etiologies, especially in the context of neuronal vulnerability, in PD and AD are likely distinct.

Notch signaling regulates limb regeneration through Hes1 and HeyL in the Chinese mitten crab

Tissue regeneration is an efficient strategy developed by animals to compensate for damaged tissues, involving various types of progenitor cells. Deciphering the signal network that modulates the activity of these progenitors during regeneration is crucial for understanding the differences in regenerative capacities across species. In this study, we evaluated the expression profile and phenotypic function of Notch signaling during limb regeneration in arthropod Chinese mitten crabs. The expression of key components of the Notch signaling pathway was upregulated at 7-day post-autotomy (7 DPA), and declined later at 18-day post-autotomy (18 DPA). To assess the role of Notch, we injected dsRNA targeting the Notch gene into the automized area and evaluated the regeneration efficiency. Our results indicated that blocking Notch signaling led to regenerative defects, manifested by delays in the wound closure and blastema emergence processes. Furthermore, the expression of Notch target genes, Hes1 and HeyL, was significantly reduced following Notch knockdown by dsRNA. Knockdown of Hes1 specifically impaired the proliferation and expression of neural progenitor cell markers, without affecting myogenic cells. In contrast, blockage of HeyL inhibited the proliferation and expression of markers in both activated neurogenic and myogenic progenitor cells, while up-regulating markers of quiescent neural progenitor cells. These findings suggest that Notch signaling plays an important role in limb regeneration of E. sinensis by activating downstream effectors Hes1 and HeyL, regulating neurogenesis and myogenesis through distinct mechanisms.

Microglia cannibalism and efferocytosis leads to shorter lifespans of developmental microglia.

The overproduction of cells and subsequent production of debris is a universal principle of neurodevelopment. Here, we show an additional feature of the developing nervous system that causes neural debris-promoted by the sacrificial nature of embryonic microglia that irreversibly become phagocytic after clearing other neural debris. Described as long-lived, microglia colonize the embryonic brain and persist into adulthood. Using transgenic zebrafish to investigate the microglia debris during brain construction, we identified that unlike other neural cell types that die in developmental stages after they have expanded, necroptosis-dependent microglial debris is prevalent when microglia are expanding in the zebrafish brain. Time-lapse imaging of microglia demonstrates that this debris is cannibalized by other microglia. To investigate features that promote microglia death and cannibalism, we used time-lapse imaging and fate-mapping strategies to track the lifespan of individual developmental microglia. These approaches revealed that instead of embryonic microglia being long-lived cells that completely digest their phagocytic debris, once most developmental microglia in zebrafish become phagocytic they eventually die, including ones that are cannibalistic. These results establish a paradox-which we tested by increasing neural debris and manipulating phagocytosis-that once most microglia in the embryo become phagocytic, they die, create debris, and then are cannibalized by other microglia, resulting in more phagocytic microglia that are destined to die.

Pathogenic mechanism and therapeutic intervention of impaired N7-methylguanosine (m7G) tRNA modification

Mutations modification enzymes including the tRNA N7-methylguanosine (m7G) methyltransferase complex component WDR4 were frequently found in patients with neural disorders, while the pathogenic mechanism and therapeutic intervention strategies are poorly explored. In this study, we revealed that patient-derived WDR4 mutation leads to temporal and cell-type-specific neural degeneration, and directly causes neural developmental disorders in mice. Mechanistically, WDR4 point mutation disrupts the interaction between WDR4 and METTL1 and accelerates METTL1 protein degradation. We further uncovered that impaired tRNA m7G modification caused by Wdr4 mutation decreases the mRNA translation of genes involved in mTOR pathway, leading to elevated endoplasmic reticulum stress markers, and increases neural cell apoptosis. Importantly, treatment with stress-attenuating drug Tauroursodeoxycholate (TUDCA) significantly decreases neural cell death and improves neural functions of the Wdr4 mutated mice. Moreover, adeno-associated virus mediated transduction of wild-type WDR4 restores METTL1 protein level and tRNA m7G modification in the mouse brain, and achieves long-lasting therapeutic effect in Wdr4 mutated mice. Most importantly, we further demonstrated that both TUDCA treatment and WDR4 restoration significantly improve the survival and functions of human iPSCs-derived neuron stem cells that harbor the patient's WDR4 mutation. Overall, our study uncovers molecular insights underlying WDR4 mutation in the pathogenesis of neural diseases and develops two promising therapeutic strategies for treatment of neural diseases caused by impaired tRNA modifications.

An ensemble convolutional neural network model for brain stroke prediction using brain computed tomography images

A stroke is a potentially fatal brain attack that causes an interruption in the blood supply to the brain. As a result, brain cells start to die due to a lack of oxygen and nutrients. After a stroke, every minute is critical. A million or more brain cells perish every minute during a stroke. The prompt identification of a stroke can prevent lasting brain damage or even save the patient’s life. Doctors advise computed tomography (CT) images of the brain for earlier stroke detection. If doctors delay CT diagnosis or may make erroneous diagnoses, this can be life-threatening. For that reason, an automatic diagnosis of stroke from a brain CT scan image will be beneficial for stroke patients. This study moderates three pre-trained convolutional neural network (CNN) models named Inceptionv3, MobileNetv2, and Xception by updating the top layer of those models using the transfer-learning technique based on CT images of the brain. A new ensemble convolutional neural network (ENSNET) model is proposed for automatic brain stroke prediction from brain CT scan images. ENSNET is the average of two improved CNN models named InceptionV3 and Xception. We have relied on the following metrics: accuracy, precision, recall, f1-score, confusion matrix, accuracy versus epoch, loss versus epoch, and the receiver operating characteristic (ROC) curve to assess performance matrices. The accuracy of the moderated Inceptionv3 is 97.48%, the moderated MobileNetv2 is 83.29%, and the moderated Xception is 96.11%. Nonetheless, the suggested ensemble model ENSNET performs better than the other models when it comes to the diagnosis of stroke from brain CT scans, providing 98.86% accuracy, 97.71% precision, 98.46% recall, 98.08% f1-score, and 98.74% area under the ROC curve(AUC). Therefore, the proposed model ENSNET can detect strokes from computed tomography images of the brain more successfully than other models.

GHRH and its analogues in central nervous system diseases.

Growth hormone-releasing hormone (GHRH) is primarily produced by the hypothalamus and stimulates the release of growth hormone (GH) in the anterior pituitary gland, which subsequently regulates the production of hepatic insulin-like growth factor-1 (IGF-1). GH and IGF-1 have potent effects on promoting cell proliferation, inhibiting cell apoptosis, as well as regulating cell metabolism. In central nerve system (CNS), GHRH/GH/IGF-1 promote brain development and growth, stimulate neuronal proliferation, and regulate neurotransmitter release, thereby participating in the regulation of various CNS physiological activities. In addition to hypothalamus-pituitary gland, GHRH and GHRH receptor (GHRH-R) are also expressed in other brain cells or tissues, such as endogenous neural stem cells (NSCs) and tumor cells. Alternations in GHRH/GH/IGF-1 axis are associated with various CNS diseases, for example, Alzheimer's disease, amyotrophic lateral sclerosis and emotional disorders manifest GHRH, GH or IGF-1 deficiency, and GH or IGF-1 supplementation exerts beneficial therapeutic effects on these diseases. CNS tumors, such as glioma, can express GHRH and GHRH-R, and activating this signaling pathway promotes tumor cell growth. The synthesized GHRH antagonists have shown to inhibit glioma cell growth and may hold promising as an adjuvant therapy for treating glioma. In addition, we have shown that GHRH agonist MR-409 can improve neurological sequelae after ischemic stroke by activating extrapituitary GHRH-R signaling and promoting endogenous NSCs-derived neuronal regeneration. This article reviews the involvement of GHRH/GH/IGF-1 in CNS diseases, and potential roles of GHRH agonists and antagonists in treating CNS diseases.

The role of mirror neurons in empathy, with a focus on their relevance in autism spectrum disorder and other clinical implications

Introduction Mirror neurons are brain cells that engage when an individual performs an action and then observes another person completing the same action. These neurons are supposed to help us grasp others' emotions and intentions by mimicking their experiences. This has led to the theory that mirror neurons influence empathy, or the ability to share and understand the experiences of others. The article investigates the role of mirror neurons in empathy, specifically their potential contribution to emotional resonance, perspective-taking, their relevance in autism spectrum disorder and other clinical implications. Aim of the study The aim of this comprehensive review is to provide an overview of how mirror neurones contribute to the development and expression of empathy in humans, with a focus on their role in autism spectrum disorder. The objective of this research is to clarify the role of mirror neurons in social cognition and gain a better understanding of the neurological foundation for empathy. Materials and methods Scientific articles from the Pubmed, Google Scholar, and Web of Science databases were analysed. The goal of this study was to choose recent articles that most adequately encompassed the problems under consideration. The search was conducted out using the following keylords: mirror neurones, empathy and autism spectrum disorder. Summary Mirror neurones appear to play an important part in empathy, as evidenced by neural activity patterns during emotion identification. While they are not the single source of empathy or the only trigger, they are definitely present. Conflicting evidence limits our understanding of their exact impact, and more credible studies need to be conducted. However, current research reveals that mirror neurones have a measurable, although limited, impact on empathy.