Human Neurological Disorders Research Articles

DVT: a high-throughput analysis pipeline for locomotion and social behavior in adult Drosophila melanogaster

BackgroundDrosophila melanogaster is excellent animal model for understanding the molecular basis of human neurological and motor disorders. The experimental conditions and chamber design varied between studies. Moreover, most previously established paradigms focus on fly trace detection algorithm development. A comprehensive understanding on how fly behaves in the chamber is still lacking.ResultsIn this report, we established 74 unique behavior metrics quantifying spatiotemporal characteristics of adult fly locomotion and social behaviors, of which 49 were newly proposed. By the aiding of the developed analysis pipeline, Drosophila video tracking (DVT), we identified siginificantly different patterns of fly behavior confronted with different chamber height, fly density, illumination and experimental time. Meanwhile, three fly strains which are widely used as control lines, Canton-S(CS), w1118 and Oregon-R (OR), were found to exhibit distinct motion explosiveness and exercise endurance.ConclusionsWe believe the proposed behavior metrics set and pipeline should help identify subtle spatial and temporal differences of drosophila behavior confronted with different environmental factors or gene variants.

Assessing Drug Administration Techniques in Zebrafish Models of Neurological Disease.

Neurological diseases, including neurodegenerative and neurodevelopmental disorders, affect nearly one in six of the world's population. The burden of the resulting deaths and disability is set to rise during the next few decades as a consequence of an aging population. To address this, zebrafish have become increasingly prominent as a model for studying human neurological diseases and exploring potential therapies. Zebrafish offer numerous benefits, such as genetic homology and brain similarities, complementing traditional mammalian models and serving as a valuable tool for genetic screening and drug discovery. In this comprehensive review, we highlight various drug delivery techniques and systems employed for therapeutic interventions of neurological diseases in zebrafish, and evaluate their suitability. We also discuss the challenges encountered during this process and present potential advancements in innovative techniques.

A SACS deletion variant in Great Pyrenees dogs causes autosomal recessive neuronal degeneration.

ARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is a human neurological disorder characterized by progressive cerebellar ataxia and peripheral neuropathy. A recently recognized disorder in Great Pyrenees dogs is similarly characterized by widespread central nervous system degeneration leading to progressive cerebellar ataxia and spasticity, combined with peripheral neuropathy. Onset of clinical signs occurred in puppies as young as 4 months of age, with slow progression over several years. A multi-generation pedigree suggested an autosomal recessive mode of inheritance. Histopathology revealed consistent cerebellar Purkinje cell degeneration, neuronal degeneration in brainstem nuclei, widespread spinal cord white matter degeneration, ganglion cell degeneration, inappropriately thin myelin sheaths or fully demyelinated peripheral nerve fibers, and normal or only mild patterns of denervation atrophy in skeletal muscles. Genome-wide single nucleotide polymorphism (SNP) genotype data was collected from 6 cases and 26 controls, where homozygosity mapping identified a 3.3Mb region on CFA25 in which all cases were homozygous and all controls were either heterozygous or homozygous for alternate haplotypes. This region tagged the SACS gene where variants are known to cause ARSACS. Sanger sequencing of SACS in affected dogs identified a 4bp deletion that causes a frame shift and truncates 343 amino acids from the C terminus of the encoded sacsin protein (p.Val4244AlafsTer32). Our clinical and histopathological descriptions of this canine disorder contribute to the description of human ARSACS and represents the first naturally occurring large animal model of this disorder.

Coordination between aminoacylation and editing to protect against proteotoxicity.

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ligate amino acids to tRNAs, and often require editing to ensure accurate protein synthesis. Recessive mutations in aaRSs cause various neurological disorders in humans, yet the underlying mechanism remains poorly understood. Pathogenic aaRS mutations frequently cause protein destabilization and aminoacylation deficiency. In this study, we report that combined aminoacylation and editing defects cause severe proteotoxicity. We show that the ths1-C268A mutation in yeast threonyl-tRNA synthetase (ThrRS) abolishes editing and causes heat sensitivity. Surprisingly, experimental evolution of the mutant results in intragenic mutations that restore heat resistance but not editing. ths1-C268A destabilizes ThrRS and decreases overall Thr-tRNAThr synthesis, while the suppressor mutations in the evolved strains improve aminoacylation. We further show that deficiency in either ThrRS aminoacylation or editing is insufficient to cause heat sensitivity, and that ths1-C268A impairs ribosome-associated quality control. Our results suggest that aminoacylation deficiency predisposes cells to proteotoxic stress.

DMCA-GAN: Dual Multilevel Constrained Attention GAN for MRI-Based Hippocampus Segmentation.

Precise segmentation of the hippocampus is essential for various human brain activity and neurological disorder studies. To overcome the small size of the hippocampus and the low contrast of MR images, a dual multilevel constrained attention GAN for MRI-based hippocampus segmentation is proposed in this paper, which is used to provide a relatively effective balance between suppressing noise interference and enhancing feature learning. First, we design the dual-GAN backbone to effectively compensate for the spatial information damage caused by multiple pooling operations in the feature generation stage. Specifically, dual-GAN performs joint adversarial learning on the multiscale feature maps at the end of the generator, which yields an average Dice coefficient (DSC) gain of 5.95% over the baseline. Next, to suppress MRI high-frequency noise interference, a multilayer information constraint unit is introduced before feature decoding, which improves the sensitivity of the decoder to forecast features by 5.39% and effectively alleviates the network overfitting problem. Then, to refine the boundary segmentation effects, we construct a multiscale feature attention restraint mechanism, which forces the network to concentrate more on effective multiscale details, thus improving the robustness. Furthermore, the dual discriminators D1 and D2 also effectively prevent the negative migration phenomenon. The proposed DMCA-GAN obtained a DSC of 90.53% on the Medical Segmentation Decathlon (MSD) dataset with tenfold cross-validation, which is superior to the backbone by 3.78%.

ATP2B2 de novo variants as a cause of variable neurodevelopmental disorders that feature dystonia, ataxia, intellectual disability, behavioral symptoms, and seizures

PurposeATP2B2 encodes the variant-constrained plasma-membrane calcium-transporting ATPase-2, expressed in sensory ear cells and specialized neurons. ATP2B2/Atp2b2 variants were previously linked to isolated hearing loss in patients and neurodevelopmental deficits with ataxia in mice. We aimed to establish the association between ATP2B2 and human neurological disorders. MethodsMultinational case recruitment, scrutiny of trio-based genomics data, in silico analyses, and functional variant characterization were performed. ResultsWe assembled 7 individuals harboring rare, predicted deleterious heterozygous ATP2B2 variants. The alleles comprised 5 missense substitutions that affected evolutionarily conserved sites and 2 frameshift variants in the penultimate exon. For 6 variants, a de novo status was confirmed. Unlike described patients with hearing loss, the individuals displayed a spectrum of neurological abnormalities, ranging from ataxia with dystonic features to complex neurodevelopmental manifestations with intellectual disability, autism, and seizures. Two cases with recurrent amino-acid variation showed distinctive overlap with cerebellar atrophy-associated ataxia and epilepsy. In cell-based studies, all variants caused significant alterations in cytosolic calcium handling with both loss- and gain-of-function effects. ConclusionPresentations in our series recapitulate key phenotypic aspects of Atp2b2-mouse models and underline the importance of precise calcium regulation for neurodevelopment and cerebellar function. Our study documents a role for ATP2B2 variants in causing heterogeneous neurodevelopmental and movement-disorder syndromes.

Differential gene expression analysis under salinity stress in the selected turmeric (Curcuma longa L.) cultivars for curcuminoid biosynthesis.

Curcuminoids are the phenolic compounds found exclusively in turmeric. Their presence is known to increase immunity and resistance against certain cancers and neurological disorders in humans also, protecting the plant itself against salinity stress. In this experiment, we studied the expression levels of MAPK1 and DCS genes, their curcuminoid biosynthesis under salinity stress conditions so that the impact of individual genes can be understood using semi- quantitative PCR. The expressions of the genes with respect to curcuminoid biosynthesis showed fluctuations in their band intensity values due to the production of curcuminoids, which is initiated first in the leaves followed by the rhizomes. Not all the genes responsible for the curcuminoid biosynthesis show positive regulation under salt stress conditions which is observed in response to the severity of the stress imposed on the cultivars. In our findings, both the genes MAPK1 and DCS were down-regulated for curcuminoid biosynthesis compared to their controls in both the cultivars Vallabh Sharad and Selection 1.

A burning question from the first international BPAN symposium: is restoration of autophagy a promising therapeutic strategy for BPAN?

ABSTRACT Beta-propeller protein-associated neurodegeneration (BPAN) is a rare neurodegenerative disease associated with severe cognitive and motor deficits. BPAN pathophysiology and phenotypic spectrum are still emerging due to the fact that mutations in the WDR45 (WD repeat domain 45) gene, a regulator of macroautophagy/autophagy, were only identified a decade ago. In the first international symposium dedicated to BPAN, which was held in Lyon, France, a panel of international speakers, including several researchers from the autophagy community, presented their work on human patients, cellular and animal models, carrying WDR45 mutations and their homologs. Autophagy researchers found an opportunity to explore the defective function of autophagy mechanisms associated with WDR45 mutations, which underlie neuronal dysfunction and early death. Importantly, BPAN is one of the few human monogenic neurological diseases targeting a regulator of autophagy, which raises the possibility that it is a relevant model to directly assess the roles of autophagy in neurodegeneration and to develop autophagy restorative therapeutic strategies for more common disorders. Abbreviations: ATG: autophagy related; BPAN: beta-propeller protein-associated neurodegeneration; ER: endoplasmic reticulum; KO: knockout; NBIA: neurodegeneration with brain iron accumulation; PtdIns3P: phosphatidylinositol-3-phosphate; ULK1: unc-51 like autophagy activating kinase 1; WDR45: WD repeat domain 45; WIPI: WD repeat domain, phosphoinositide interacting.

LncRNAs: the good, the bad, and the unknown.

Long non-coding RNAs (lncRNAs) are significant contributors in maintaining genomic integrity through epigenetic regulation. LncRNAs can interact with chromatin-modifying complexes in both cis and trans pathways, drawing them to specific genomic loci and influencing gene expression via DNA methylation, histone modifications, and chromatin remodeling. They can also operate as building blocks to assemble different chromatin-modifying components, facilitating their interactions and gene regulatory functions. Deregulation of these molecules has been associated with various human diseases, including cancer, cardiovascular disease, and neurological disorders. Thus, lncRNAs are implicated as potential diagnostic indicators and therapeutic targets. This review discusses the current understanding of how lncRNAs mediate epigenetic control, genomic integrity, and their putative functions in disease pathogenesis.

Advancing therapeutics using antibody-induced dimerization of receptor tyrosine phosphatases.

Receptor protein tyrosine phosphatases (RPTPs) are involved in a broad list of cellular, developmental, and physiological functions. Altering their expression leads to significant changes in protein phosphorylation linked to a growing list of human diseases, including cancers and neurological disorders. In this issue of Genes & Development, Qian and colleagues (pp. 743-759) present the identification of a monoclonal antibody targeting PTPRD extracellular domain-inducing dimerization and inhibition of the phosphatase activities, causing the proteolysis of dimeric PTPRD by a mechanism involving intracellular degradation pathways. Their study supports the potential of modulating PTPRD via its extracellular domains. This opens a new framework in the clinical manipulation of PTPRD and its closely related family members.

The Pig as a Translational Animal Model for Biobehavioral and Neurotrauma Research.

In recent decades, the pig has attracted considerable attention as an important intermediary model animal in translational biobehavioral research due to major similarities between pig and human neuroanatomy, physiology, and behavior. As a result, there is growing interest in using pigs to model many human neurological conditions and injuries. Pigs are highly intelligent and are capable of performing a wide range of behaviors, which can provide valuable insight into the effects of various neurological disease states. One area in which the pig has emerged as a particularly relevant model species is in the realm of neurotrauma research. Indeed, the number of investigators developing injury models and assessing treatment options in pigs is ever-expanding. In this review, we examine the use of pigs for cognitive and behavioral research as well as some commonly used physiological assessment methods. We also discuss the current usage of pigs as a model for the study of traumatic brain injury. We conclude that the pig is a valuable animal species for studying cognition and the physiological effect of disease, and it has the potential to contribute to the development of new treatments and therapies for human neurological and psychiatric disorders.

Ifit2 restricts murine coronavirus spread to the spinal cord white matter and its associated myelin pathology.

Interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is critical in restricting neurotropic murine-β-coronavirus, RSA59 infection. RSA59 intracranial injection of Ifit2-deficient (-/-) compared to wild-type (WT) mice results in impaired acute microglial activation, reduced CX3CR1 expression, limited migration of peripheral lymphocytes into the brain, and impaired virus control followed by severe morbidity and mortality. While the protective role of Ifit2 is established for acute viral encephalitis, less is known about its influence during the chronic demyelinating phase of RSA59 infection. To understand this, RSA59 infected Ifit2-/- and Ifit2+/+ (WT) were observed for neuropathological outcomes at day 5 (acute phase) and 30 post-infection (chronic phase). Our study demonstrates that Ifit2 deficiency causes extensive RSA59 spread throughout the spinal cord gray and white matter, associated with impaired CD4+ T and CD8+ T cell infiltration. Further, the cervical lymph nodes of RSA59 infected Ifit2-/- mice showed reduced activation of CD4+ T cells and impaired IFNγ expression during acute encephalomyelitis. Interestingly, BBB integrity was better preserved in Ifit2-/- mice, as evidenced by tight junction protein Claudin-5 and adapter protein ZO-1 expression surrounding the meninges and blood vessels and decreased Texas red dye uptake, which may be responsible for reduced leukocyte infiltration. In contrast to sparse myelin loss in WT mice, the chronic disease phase in Ifit2-/- mice was associated with severe demyelination and persistent viral load, even at low inoculation doses. Overall, our study highlights that Ifit2 provides antiviral functions by promoting acute neuroinflammation and thereby aiding virus control and limiting severe chronic demyelination. IMPORTANCE Interferons execute their function by inducing specific genes collectively termed as interferon-stimulated genes (ISGs), among which interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is known for restricting neurotropic viral replication and spread. However, little is known about its role in viral spread to the spinal cord and its associated myelin pathology. Toward this, our study using a neurotropic murine β-coronavirus and Ifit2-deficient mice demonstrates that Ifit2 deficiency causes extensive viral spread throughout the gray and white matter of the spinal cord accompanied by impaired microglial activation and T cell infiltration. Furthermore, infected Ifit2-deficient mice showed impaired activation of T cells in the cervical lymph node and relatively intact blood-brain barrier integrity. Overall, Ifit2 plays a crucial role in mounting host immunity against neurotropic murine coronavirus in the acute phase while preventing mice from developing viral-induced severe chronic neuroinflammatory demyelination, the characteristic feature of human neurological disease multiple sclerosis (MS).

Co-Circulation of Coronaviruses among Rodents and Insectivores

Coronaviruses (family Coronaviridae, genera Alphacoronavirus and Betacoronavirus) are the causative agents of respiratory, intestinal and neurological diseases in humans and animals. Natural reservoirs of coronaviruses include bats, rodents and insectivores, however, the circulation of coronaviruses among rodents and insectivores in the Russian Federation has been unexplored. The aim of the study was to investigate the diversity of coronaviruses among rodents and insectivores co-inhabiting natural biotopes. Materials and methods. Rodents (68 specimens) and shrews of the genus Sorex (23 specimens) were caught in a limited forest area not exceeding 1.5 sq. km, in the vicinity of Novosibirsk. All samples were screened using reverse transcription polymerase chain reaction followed by sequencing. Results and discussion. Four distinct coronaviruses have been detected in four species of small mammals. Rodent-borne coronaviruses were classed within subgenera Embecovirus, genus Betacoronavirus, and demonstrated host-associated phylogenetic clustering. The level of homology between the new RNA isolates from red-backed vole (Myodes rutilus), root vole (Microtus oeconomus) and field mouse (Apodemus agrarius) is 85.5–87.7 %. The nucleotide sequences of Siberian coronavirus isolates are closely related (>93 % homology) to previously published sequences in each of the carrier groups found in Europe and China, which suggests their common evolutionary origin. The coronavirus identified in the common shrew (Sorex araneus) belongs to the genus Alphacoronavirus, but is significantly different (>36 % difference) from earlier identified strains included in the genus. It has been shown that different coronaviruses co-circulate in a limited area among rodents and insectivores.

An intellectual-disability-associated mutation of the transcriptional regulator NACC1 impairs glutamatergic neurotransmission.

Advances in genome sequencing technologies have favored the identification of rare de novo mutations linked to neurological disorders in humans. Recently, a de novo autosomal dominant mutation in NACC1 was identified (NM_052876.3: c.892C > T, NP_443108.1; p.Arg298Trp), associated with severe neurological symptoms including intellectual disability, microcephaly, and epilepsy. As NACC1 had never before been associated with neurological diseases, we investigated how this mutation might lead to altered brain function. We examined neurotransmission in autaptic glutamatergic mouse neurons expressing the murine homolog of the human mutant NACC1, i.e., Nacc1-R284W. We observed that expression of Nacc1-R284W impaired glutamatergic neurotransmission in a cell-autonomous manner, likely through a dominant negative mechanism. Furthermore, by screening for Nacc1 interaction targets in the brain, we identified SynGAP1, GluK2A, and several SUMO E3 ligases as novel Nacc1 interaction partners. At a biochemical level, Nacc1-R284W exhibited reduced binding to SynGAP1 and GluK2A, and also showed greatly increased SUMOylation. Ablating the SUMOylation of Nacc1-R284W partially restored its interaction with SynGAP1 but did not restore binding to GluK2A. Overall, these data indicate a role for Nacc1 in regulating glutamatergic neurotransmission, which is substantially impaired by the expression of a disease-associated Nacc1 mutant. This study provides the first functional insights into potential deficits in neuronal function in patients expressing the de novo mutant NACC1 protein.

Germline pathogenic variants in HNRNPU are associated with alterations in blood methylome

HNRNPU encodes a multifunctional RNA-binding protein that plays critical roles in regulating pre-mRNA splicing, mRNA stability, and translation. Aberrant expression and dysregulation of HNRNPU have been implicated in various human diseases, including cancers and neurological disorders. We applied a next generation sequencing based assay (EPIC-NGS) to investigate genome-wide methylation profiling for >2 M CpGs for 7 individuals with a neurodevelopmental disorder associated with HNRNPU germline pathogenic loss-of-function variants. Compared to healthy individuals, 227 HNRNPU-associated differentially methylated positions were detected. Both hyper- and hypomethylation alterations were identified but the former predominated. The identification of a methylation episignature for HNRNPU-associated neurodevelopmental disorder (NDD) implicates HNPRNPU-related chromatin alterations in the aetiopathogenesis of this disorder and suggests that episignature profiling should have clinical utility as a predictor for the pathogenicity of HNRNPU variants of uncertain significance. The detection of a methylation episignaure for HNRNPU-associated NDD is consistent with a recent report of a methylation episignature for HNRNPK-associated NDD.

Rational Design and Acoustic Assembly of Human Cerebral Cortex-Like Microtissues from hiPSC-Derived Neural Progenitors and Neurons.

Development of biologically relevant and clinically relevant human cerebral cortex models is demanded by mechanistic studies of human cerebral cortex-associated neurological diseases and discovery of preclinical neurological drug candidates. Here, rational design of human-sourced brain-like cortical tissue models is demonstrated by reverse engineering and bionic design. To implement this design, the acoustic assembly technique is employed to assemble hiPSC-derived neural progenitors and neurons separately in a label-free and contact-free manner followed by subsequent neural differentiation and culture. The generated microtissues encapsulate the neuronal microanatomy of human cerebral-cortex tissue that contains six-layered neuronal architecture, a 400-µm interlayer distance, synaptic connections between interlayers, and neuroelectrophysiological transmission. Furthermore, these microtissues are infected with herpes simplex virus type I (HSV-1)virus, and the HSV-induced pathogenesis associated with Alzheimer's disease is determined, including neuron loss and the expression of Aβ. Overall, a high-fidelity human-relevant in vitro histotypic model is provided for thecerebral cortex, which will facilitate wide applications in probing the mechanisms of neurodegenerative diseases and screening the candidates for neuroprotective agents.

Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations

BackgroundYungui Plateau in Southwest China is characterized by multi-language and multi-ethnic communities and is one of the regions with the wealthiest ethnolinguistic, cultural and genetic diversity in East Asia. There are numerous Tai-Kadai (TK)-speaking populations, but their detailed evolutionary history and biological adaptations are still unclear.ResultsHere, we genotyped genome-wide SNP data of 77 unrelated TK-speaking Zhuang and Dong individuals from the Yungui Plateau and explored their detailed admixture history and adaptive features using clustering patterns, allele frequency differentiation and sharing haplotype patterns. TK-speaking Zhuang and Dong people in Guizhou are closely related to geographically close TK and Hmong-Mien (HM)-speaking populations. Besides, we identified that Guizhou TK-speaking people have a close genetic relationship with Austronesian (AN)-speaking Atayal and Paiwan people, which is supported by the common origin of the ancient Baiyue tribe. We additionally found subtle genetic differences among the newly studied TK people and previously reported Dais via the fine-scale genetic substructure analysis based on the shared haplotype chunks. Finally, we identified specific selection candidate signatures associated with several essential human immune systems and neurological disorders, which could provide evolutionary evidence for the allele frequency distribution pattern of genetic risk loci.ConclusionsOur comprehensive genetic characterization of TK people suggested the strong genetic affinity within TK groups and extensive gene flow with geographically close HM and Han people. We also provided genetic evidence that supported the common origin hypothesis of TK and AN people. The best-fitted admixture models further suggested that ancestral sources from northern millet farmers and southern inland and coastal people contributed to the formation of the gene pool of the Zhuang and Dong people.

Natural product-derived therapies for treating drug-resistant epilepsies: From ethnopharmacology to evidence-based medicine

Ethnopharmacological relevanceEpilepsy is one of the most prevalent neurological human diseases, affecting 1% of the population in all age groups. Despite the availability of over 25 anti-seizure medications (ASMs), which are approved in most industrialized countries, approximately 30% of epilepsy patients still experience seizures that are resistant to these drugs. Since ASMs target only limited number of neurochemical mechanisms, drug-resistant epilepsy (DRE) is not only an unmet medical need, but also a formidable challenge in drug discovery. AimIn this review, we examine recently approved epilepsy drugs based on natural product (NP) such as cannabidiol (CBD) and rapamycin, as well as NP-based epilepsy drug candidates still in clinical development, such as huperzine A. We also critically evaluate the therapeutic potential of botanical drugs as polytherapy or adjunct therapy specifically for DRE. MethodsArticles related to ethnopharmacological anti-epileptic medicines and NPs in treating all forms of epilepsy were collected from PubMed and Scopus using keywords related to epilepsy, DRE, herbal medicines, and NPs. The database clinicaltrials.gov was used to find ongoing, terminated and planned clinical trials using herbal medicines or NPs in epilepsy treatment. ResultsA comprehensive review on anti-epileptic herbal drugs and natural products from the ethnomedical literature is provided. We discuss the ethnomedical context of recently approved drugs and drug candidates derived from NPs, including CBD, rapamycin, and huperzine A. Recently published studies on natural products with preclinical efficacy in animal models of DRE are summarized. Moreover, we highlight that natural products capable of pharmacologically activating the vagus nerve (VN), such as CBD, may be therapeutically useful to treat DRE. ConclusionsThe review highlights that herbal drugs utilized in traditional medicine offer a valuable source of potential anti-epileptic drug candidates with novel mechanisms of action, and with clinical promise for the treatment of drug-resistant epilepsy (DRE). Moreover, recently developed NP-based anti-seizure medications (ASMs) indicate the translational potential of metabolites of plant, microbial, fungal and animal origin.

Virus infection participates in the occurrence and development of human diseases through monoamine oxidase.

Monoamine oxidase (MAO) is a membrane-bound mitochondrial enzyme that maintains the steady state of neurotransmitters and other biogenic amines in biological systems through catalytic oxidation and deamination. MAO dysfunction is closely related to human neurological and psychiatric diseases and cancers. However, little is known about the relationship between MAO and viral infections in humans. This review summarises current research on how viral infections participate in the occurrence and development of human diseases through MAO. The viruses discussed in this review include hepatitis C virus, dengue virus, severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus, Japanese encephalitis virus, Epstein-Barr virus, and human papillomavirus. This review also describes the effects of MAO inhibitors such as phenelzine, clorgyline, selegiline, M-30, and isatin on viral infectious diseases. This information will not only help us to better understand the role of MAO in the pathogenesis of viruses but will also provide new insights into the treatment and diagnosis of these viral diseases.

Imaging Approaches to Investigate Pathophysiological Mechanisms of Brain Disease in Zebrafish.

Zebrafish has become an essential model organism in modern biomedical research. Owing to its distinctive features and high grade of genomic homology with humans, it is increasingly employed to model diverse neurological disorders, both through genetic and pharmacological intervention. The use of this vertebrate model has recently enhanced research efforts, both in the optical technology and in the bioengineering fields, aiming at developing novel tools for high spatiotemporal resolution imaging. Indeed, the ever-increasing use of imaging methods, often combined with fluorescent reporters or tags, enable a unique chance for translational neuroscience research at different levels, ranging from behavior (whole-organism) to functional aspects (whole-brain) and down to structural features (cellular and subcellular). In this work, we present a review of the imaging approaches employed to investigate pathophysiological mechanisms underlying functional, structural, and behavioral alterations of human neurological diseases modeled in zebrafish.