Complex Neurological Disorder Research Articles

Bi-allelic variants in the ectonucleotidase ENTPD1 cause a complex neurological disease consisting of intellectual disability, brain abnormalities, and spastic paraplegia (2093)

Bi-allelic variants in the ectonucleotidase ENTPD1 cause a complex neurological disease consisting of intellectual disability, brain abnormalities, and spastic paraplegia (2093)

Engineering in vitro human neural tissue analogs by 3D bioprinting and electrostimulation.

There is a fundamental need for clinically relevant, reproducible, and standardized in vitro human neural tissue models, not least of all to study heterogenic and complex human-specific neurological (such as neuropsychiatric) disorders. Construction of three-dimensional (3D) bioprinted neural tissues from native human-derived stem cells (e.g., neural stem cells) and human pluripotent stem cells (e.g., induced pluripotent) in particular is appreciably impacting research and conceivably clinical translation. Given the ability to artificially and favorably regulate a cell's survival and behavior by manipulating its biophysical environment, careful consideration of the printing technique, supporting biomaterial and specific exogenously delivered stimuli, is both required and advantageous. By doing so, there exists an opportunity, more than ever before, to engineer advanced and precise tissue analogs that closely recapitulate the morphological and functional elements of natural tissues (healthy or diseased). Importantly, the application of electrical stimulation as a method of enhancing printed tissue development in vitro, including neuritogenesis, synaptogenesis, and cellular maturation, has the added advantage of modeling both traditional and new stimulation platforms, toward improved understanding of efficacy and innovative electroceutical development and application.

Application of CGRP-Related Monoclonal Antibodies in Migraine Management

Migraine is a common and debilitating neurological disorder characterized by recurrent headaches of moderate-to-severe intensity. Because of its high prevalence, migraine causes a considerable financial burden on society. There is ample evidence showing that migraine is a complex neurological disorder that involves not only the trigeminovascular and autonomic systems, but also the hypothalamus and cerebral cortex. Calcitonin gene-related peptide (CGRP) was originally discovered as a 37-amino acid neuropeptide derived from a calcitonin gene splicing variant, is enriched in trigeminal ganglion neurons. Much attention has been paid to CGRP since it was found to be released from trigeminal terminals in animal migraine models. Subsequent studies demonstrated that CGRP administration induced migraine-like headaches specifically in migraineurs, thus highlighting its pivotal role CGRP in the development of migraine attacks. Monoclonal antibodies targeting CGRP and its receptor exhibited consistent efficacy for migraine prophylaxis with excellent safety profiles in clinical trials. Furthermore, emerging data support the long-term safety and efficacy of these antibodies. On the other hand, there are several concerns that have newly surfaced in the real-world setting. In this review, the development and perspective of anti-migraine therapeutic strategies using CGRP-related antibodies are discussed.

Immunohistological Examination of AKT Isoforms in the Brain: Cell-Type Specificity That May Underlie AKT's Role in Complex Brain Disorders and Neurological Disease.

Protein kinase B (PKB/AKT) is a central kinase involved in many neurobiological processes. AKT is expressed in the brain as three isoforms, AKT1, AKT2, and AKT3. Previous studies suggest isoform-specific roles in neural function, but very few studies have examined AKT isoform expression at the cellular level. In this study, we use a combination of histology, immunostaining, and genetics to characterize cell-type-specific expression of AKT isoforms in human and mouse brains. In mice, we find that AKT1 is the most broadly expressed isoform, with expression in excitatory neurons and the sole detectable AKT isoform in gamma-aminobutyric acid ergic interneurons and microglia. By contrast, we find that AKT2 is the sole isoform expressed in astroglia and is not detected in other neural cell types. We find that AKT3 is expressed in excitatory neurons with AKT1 but shows greater expression levels in dendritic compartments than AKT1. We extend our analysis to human brain tissues and find similar results. Using genetic deletion approaches, we also find that the cellular determinants restricting AKT isoform expression to specific cell types remain intact under Akt deficiency conditions. Because AKT signaling is linked to numerous neurological disorders, a greater understanding of cell-specific isoform expression could improve treatment strategies involving AKT.

The Implementation Science for Genomic Health Translation (INSIGHT) Study in Epilepsy: Protocol for a Learning Health Care System.

BackgroundGenomic medicine is poised to improve care for common complex diseases such as epilepsy, but additional clinical informatics and implementation science research is needed for it to become a part of the standard of care. Epilepsy is an exemplary complex neurological disorder for which DNA diagnostics have shown to be advantageous for patient care.ObjectiveWe designed the Implementation Science for Genomic Health Translation (INSIGHT) study to leverage the fact that both the clinic and testing laboratory control the development and customization of their respective electronic health records and clinical reporting platforms. Through INSIGHT, we can rapidly prototype and benchmark novel approaches to incorporating clinical genomics into patient care. Of particular interest are clinical decision support tools that take advantage of domain knowledge from clinical genomics and can be rapidly adjusted based on feedback from clinicians.MethodsBuilding on previously developed evidence and infrastructure components, our model includes the following: establishment of an intervention-ready genomic knowledge base for patient care, creation of a health informatics platform and linking it to a clinical genomics reporting system, and scaling and evaluation of INSIGHT following established implementation science principles.ResultsINSIGHT was approved by the Institutional Review Board at the University of Texas Health Science Center at Houston on May 15, 2020, and is designed as a 2-year proof-of-concept study beginning in December 2021. By design, 120 patients from the Texas Comprehensive Epilepsy Program are to be enrolled to test the INSIGHT workflow. Initial results are expected in the first half of 2023.ConclusionsINSIGHT’s domain-specific, practical but generalizable approach may help catalyze a pathway to accelerate translation of genomic knowledge into impactful interventions in patient care.International Registered Report Identifier (IRRID)PRR1-10.2196/25576

Validation of an ASIC1a Ligand-Gated Assay on an Automated Patch Clamp Platform and its Use for Novel Ligand Screening

There is growing interest in automated patch clamp assays for ligand-gated targets, many of which are expressed throughout the nervous system and underlie complex neurological diseases. The Acid-Sensing Ion Channel (ASIC) family comprises combinations of ASIC1-4 proteins that form cation-selective channels in the central and peripheral nervous system. ASIC1a proteins are involved in synaptic plasticity, and implicated in stroke, ischemia and pain. Small molecules and toxins modulate ASIC1a channels, and fragments can bind to ASIC3 channels (Wolkenberg et al., 2010), so we screened a diverse low molecular weight library for novel ASIC1a modulators. All data was generated on the gigaseal QPatch48 system (Sophion) using coated metal pipetting tips and a CHO cell line stably expressing human ASIC1a. Currents were elicited from a holding potential of −60 mV by rapid application of saline or compound-containing solutions of varied pH. EC50 of pH activation and IC50 of test compound inhibition were determined by cumulative applications to the same cell. A proprietary low MW library was tested at 200 μM (N=2) and active hits were confirmed by cumulative IC50 testing (N=3). We validated the pharmacology of the hASIC1a cell line using toxins (e.g. IC50 of 120 nM for Mambalgin-3), small molecules (Benzamil IC50 of 4.0 μM), and clinical development compounds, which paved the way to screen a proprietary library of low molecular weight compounds in an effort to find chemical building blocks for the design of novel and efficacious ASIC1a modulators. A hit rate of 3.0% was achieved which included several novel scaffolds with low μM potency, which can be used in biophysical binding assays and structure-based drug design to develop ligand-efficient modulators of the human ASIC1a channel.

Chronic Intermittent Hypobaric Hypoxia Restores Hippocampus Function and Rescues Cognitive Impairments in Chronic Epileptic Rats via Wnt/β-catenin Signaling.

Epilepsy is a complex neurological disorder with frequent psychiatric, cognitive, and social comorbidities in addition to recurrent seizures. Cognitive impairment, one of the most common comorbidities, has severe adverse effects on quality of life. Chronic intermittent hypobaric hypoxia (CIHH) has demonstrated neuroprotective efficacy in several neurological disease models. In the present study, we examined the effects of CIHH on cognition and hippocampal function in chronic epileptic rats. CIHH treatment rescued deficits in spatial and object memory, hippocampal neurogenesis, and synaptic plasticity in pilocarpine-treated epileptic rats. The Wnt/β-catenin pathway has been implicated in neural stem cell proliferation and synapse development, and Wnt/β-catenin pathway inhibition effectively blocked the neurogenic effects of CIHH. Our findings indicate that CIHH rescues cognitive deficits in epileptic rats via Wnt/β-catenin pathway activation. This study establishes CIHH and Wnt/β-catenin pathway regulators as potential treatments for epilepsy- induced cognitive impairments.

Nanotheranostics in epilepsy: A perspective for multimodal diagnosis and strategic management

AbstractEpilepsy is a common but a complex neurological disorder with limited practices for successful management due to the complicated neuronal network and lack of knowledge of epileptic pathophysiology. Theranostic systems such as implantable devices and biodegradable nanomaterials offer better tailor‐made methods for the detection and treatment using nanotechnology‐based approaches for patients with epilepsy. Miniaturized nano‐implantable devices and biosensors equipped with operations to mimic neurostimulation demonstrate excellent opportunities in profiling the disease and assist in comprehension of the relationship between the disease and host. This strategy is developed for diagnoses and mapping brain activities to integrate and target therapeutic nanosystems in epilepsy. Non‐invasive class of nanotheranostics such as biodegradable and stimuli‐responsive polymers includes nanomaterials that utilize bio‐physico‐chemical processes or stimuli as a source for detecting the state and progress of the disease. The superior form of nanotheranostics encompasses in‐situ diagnostics with triggered release at the specific site. This review article focuses on the nanotheranostic strategies for epilepsy, their implications, challenges and new potentials for detection and therapy in personalized medicine. The concept of “on‐demand” release of drugs at the site of action using bio‐responsive theranostic approach reveals a potential for developing a point of primary care for epilepsy in the future.

Stem-cell-derived human microglia transplanted into mouse brain to study human disease.

Microglia are critically involved in complex neurological disorders with a strong genetic component, such as Alzheimer's disease, Parkinson's disease and frontotemporal dementia. Although mouse microglia can recapitulate aspects of human microglia physiology, they do not fully capture the human genetic aspects of disease and do not reproduce all human cell states. Primary cultures of human microglia or microglia derived from human induced pluripotent stem cells (PSCs) are difficult to maintain in brain-relevant cell states in vitro. Here we describe MIGRATE (microglia in vitro generation refined for advanced transplantation experiments, which provides a combined in vitro differentiation and in vivo xenotransplantation protocol to study human microglia in the context of the mouse brain. This article details an accurate, step-by-step workflow that includes in vitro microglia differentiation from human PSCs, transplantation into the mouse brain and quantitative analysis of engraftment. Compared to current differentiation and xenotransplantation protocols, we present an optimized, faster and more efficient approach that yields up to 80% chimerism. To quantitatively assess engraftment efficiency by flow cytometry, access to specialized flow cytometry is required. Alternatively, the percentage of chimerism can be estimated by standard immunohistochemical analysis. The MIGRATE protocol takes ~40 d to complete, from culturing PSCs to engraftment efficiency assessment.

Comparative Analysis of Chemotherapy-Induced Peripheral Neuropathy in Bioengineered Sensory Nerve Tissue Distinguishes Mechanistic Differences in Early-Stage Vincristine-, Cisplatin-, and Paclitaxel-Induced Nerve Damage.

Chemotherapy-induced peripheral neuropathy (CIPN) is a well-known, potentially permanent side effect of widely used antineoplastic agents. The mechanisms of neuropathic progression are poorly understood, and the need to test efficacy of novel interventions to treat CIPN continues to grow. Bioengineered microphysiological nerve tissue ("nerve on a chip") has been suggested as an in vitro platform for modeling the structure and physiology of in situ peripheral nerve tissue. Here, we find that length-dependent nerve conduction and histopathologic changes induced by cisplatin, paclitaxel, or vincristine in rat dorsal root ganglion-derived microphysiological sensory nerve tissue recapitulate published descriptions of clinical electrophysiological changes and neuropathologic biopsy findings in test animals and human patients with CIPN. We additionally confirm the postulated link between vincristine-induced axoplasmic transport failure and functional impairment of nerve conduction, the postulated paclitaxel-induced somal toxicity, and identify a potential central role of gliotoxicity in cisplatin-induced sensory neuropathy. Microphysiological CIPN combines the tight experimental control afforded by in vitro experimentation with clinically relevant functional and structural outputs that conventionally require in vivo models. Microphysiological nerve tissue provides a low-cost, high-throughput alternative to conventional nonclinical models for efficiently and effectively investigating lesions, mechanisms, and treatments of CIPN. Neural microphysiological systems are capable of modeling complex neurological disease at the tissue level offering unique advantages over conventional methodology for both testing and generating hypotheses in neurological disease modeling. Impact Statement Recapitulation of distinct hallmarks of clinical CIPN in microphysiological sensory nerve validates a novel peripheral neurotoxicity model with unique advantages over conventional model systems.

Gender influence on antioxidant capacity and oxidative damage in saliva of children with autism spectrum disorder: a preliminary study

Abstract Introduction Autism is a complex neurological disorder with multifactorial causes, which compromises physical, psychological, emotional and social skills. This disorder also impairs dental care and patient oral health. Saliva can be easily obtained using a non-invasive technique and has been used in the diagnosis and screening of many pathologies. Total antioxidant capacity of saliva is reduced in the presence of caries in children and has been studied as a possible marker for autism. However, data on salivary antioxidants in children with autism spectrum disorder (ASD) is scarce. Objective This preliminary study evaluated the existence of gender influence on non-enzymatic antioxidant capacity and protein oxidative damage in the saliva of children with this disorder. Our hypothesis is that there are gender differences in these biochemical parameters in children with austim. Material and method Whole saliva samples were collected by aspiration between 8:00-11:00 am from 12 girls and 12 boys aged 5 to 15 years, with previous diagnosis for this disorder. Total antioxidant capacity, uric acid, protein concentration and oxidative damage to proteins were analyzed by spectrophotometry. Values were presented as mean ± standard deviation and tested for adherence to normality (Shapiro-Wilk test). The data were then compared using the Mann-Whitney test, considering a 5% significance level. Result There was no significant difference between groups for all analyzed parameters (P>0.05). Conclusion Based on the results obtained, we concluded that gender does not influence the levels of oxidative stress markers in the saliva of children with ASD.

Childhood Hydrocephalus in Sokoto: Experience with 401 Series.

ABSTRACTBackground:Hydrocephalus is a complex and multifactorial neurological disorders. Childhood hydrocephalus like other chronic childhood illness is a major contributor to poor quality of life and huge financial burden to the affected family and nation. Epidemiological factors tend to vary with geographical location. Unlike in developed countries, most data from developing countries showed infection as the most common etiology. This study was conducted to analyze our epidemiological features of childhood hydrocephalus in Sokoto with a review of the literature.Aims:The aims of this study were to determine the frequency of causes of hydrocephalus in Sokoto and to determine the short-term outcomes of treatment and compare results with the literatures.Materials and Methods:This was a retrospective study with patients’ data from the theatre records, patients’ case notes, and radiological records. Outcomes were based on complications and changes in the occipitofrontal circumferences. Criteria for statistical significant was P < 0.05.Results:One hundred and thirty-eight patients satisfied inclusion criteria. No sex preponderance was found with a mean age of 16.41 months. Maternal illiteracy rate was 60% with 49.3% of the parents at lower socioeconomic class. Infection was the most frequent etiology (45.7%). Myelomeningocele associated hydrocephalus was also common (16.7%). However, post-hemorrhagic hydrocephalus was rare (2.9%). Mean preoperative and postoperative occipitofrontal circumferences were 54.22 cm and 47.92 cm, respectively, with P = 0.001.Conclusion:Poverty and illiteracy were strongly associated with childhood hydrocephalus in our patients. Infection was predominantly associated with morbidity with large number of patients being lost to follow-up.

Migraine attacks as a result of hypothalamic loss of control

Migraine is a complex neurological disorder affecting approximately 12% of the population. The pathophysiology is not yet fully understood, however the clinical features of the disease, such as the cyclic behaviour of attacks and vegetative symptoms, suggest a prominent role of the hypothalamus. Previous research has observed neuronal alterations at different time points during the migraine interval, specifically just before the headache is initiated. We therefore aimed to assess the trajectory of migraineurs’ brain activity over an entire migraine cycle.Using functional magnetic resonance imaging (fMRI) with pseudo-continuous arterial spin labelling (ASL), we designed a longitudinal intra-individual study to detect the rhythmicity of (1) the cerebral perfusion and (2) the hypothalamic connectivity over an entire migraine cycle. Twelve episodic migraine patients were examined in 82 sessions during spontaneous headache attacks with follow-up recordings towards the next attack.We detected cyclic changes of brain perfusion in the limbic circuit (insula and nucleus accumbens), with the highest perfusion during the headache attack. In addition, we found an increase of hypothalamic connectivity to the limbic system over the interictal interval towards the attack, then collapsing during the headache phase.The present data provide strong evidence for the predominant role of the hypothalamus in generating migraine attacks. Due to a genetically-determined cortical hyperexcitability, migraineurs are most likely characterised by an increased susceptibility of limbic neurons to the known migraine trigger. The hypothalamus as a metronome of internal processes is suggested to control these limbic circuits: migraine attacks may occur as a result of the hypothalamus losing control over the limbic system. Repetitive psychosocial stress, one of the leading trigger factors reported by patients, might make the limbic system even more vulnerable and lead to a premature triggering of a migraine attack. Potential therapeutic interventions are therefore suggested to strengthen limbic circuits with dedicated medication or psychological approaches.

Neuroprotective Effects of the Anti-cancer Drug Lapatinib Against Epileptic Seizures via Suppressing Glutathione Peroxidase 4-Dependent Ferroptosis.

Epilepsy is a complex neurological disorder characterized by recurrent and unprovoked seizures. Neuronal death process is implicated in the development of repetitive epileptic seizures. Therefore, cell death can be harnessed for ceasing seizures and epileptogenesis. Oxidative stress is regarded as a contributing factor of neuronal death activation and there is compelling evidence supporting antioxidants hold promise in abrogating seizure-related cell modality. Lapatinib, a well-known anti-cancer drug, has been traditionally reported to exert anti-tumor effect via modulating oxidative stress and a recent work illustrates the improvement of encephalomyelitis in rodent models after lapatinib treatment. However, whether lapatinib is beneficial for inhibiting neuronal death and epileptic seizure remains unknown. Here, we found that lapatinib remarkably prevented kainic acid (KA)-epileptic seizures in mice and ferroptosis, a newly defined cell death which is associated with oxidative stress, was involved in the neuroprotection of lapatinib. In the ferroptotic cell death model, lapatinib exerted neuroprotection via restoring glutathione peroxidase 4 (GPX4). Treatment with GPX4 inhibitor ras-selective lethal small molecule 3 (RSL3) abrogated its anti-ferroptotic potential. In a mouse model of KA-triggered seizure, it was also validated that lapatinib blocked GPX4-dependent ferroptosis. It is concluded that lapatinib has neuroprotective potential against epileptic seizures via suppressing GPX4-mediated ferroptosis.

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Parkinson's disease (PD) is a complex neurological disorder characterized by motor and nonmotor symptoms. The onset of visual symptoms may occur many years before motor ones. Growing evidence shows a strong involvement of the visual system, including corneal changes, retinal layer thinning, and alterations of gray and white matter. These modifications can explain the wide range of visual symptoms, including visual acuity loss, eye movements and pupillary defects, electrophysiology alterations, and visual processing impairment.Moreover, visual symptoms and visual system involvement also can be detected in other forms of parkinsonism, such as Lewy body dementia and multiple system atrophy. However, the deep characterization of common features and differences between each parkinsonism, in terms of visual system changes, is still missing.The main aim of the present chapter is to describe the main alterations reported in the literature of the visual system in PD.

Functional Comparison of Blood-Derived Human Neural Progenitor Cells.

Induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) are promising tools to model complex neurological or psychiatric diseases, including schizophrenia. Multiple studies have compared patient-derived and healthy control NPCs derived from iPSCs in order to investigate cellular phenotypes of this disease, although the establishment, stabilization, and directed differentiation of iPSC lines are rather expensive and time-demanding. However, interrupted reprogramming by omitting the stabilization of iPSCs may allow for the generation of a plastic stage of the cells and thus provide a shortcut to derive NPSCs directly from tissue samples. Here, we demonstrate a method to generate shortcut NPCs (sNPCs) from blood mononuclear cells and present a detailed comparison of these sNPCs with NPCs obtained from the same blood samples through stable iPSC clones and a subsequent neural differentiation (classical NPCs—cNPCs). Peripheral blood cells were obtained from a schizophrenia patient and his two healthy parents (a case–parent trio), while a further umbilical cord blood sample was obtained from the cord of a healthy new-born. The expression of stage-specific markers in sNPCs and cNPCs were compared both at the protein and RNA levels. We also performed functional tests to investigate Wnt and glutamate signaling and the oxidative stress, as these pathways have been suggested to play important roles in the pathophysiology of schizophrenia. We found similar responses in the two types of NPCs, suggesting that the shortcut procedure provides sNPCs, allowing an efficient screening of disease-related phenotypes.

Digesting science: Developing educational activities about multiple sclerosis, prevention and treatment to increase the confidence of affected families

BackgroundThe majority of information sources for children of people with multiple sclerosis (MS) are paper, or text, based and require high levels of literacy. ObjectiveTo develop educational activities to inform children who have a parent with MS about a number of aspects around MS and to improve the confidence levels of both parents and children to discuss MS. MethodsA structured interactive event, Digesting Science (DS), was developed. This covers the effect MS can have on: vision, bladder function, walking, the mechanisms of action of disease-modifying treatments, the potential importance of vitamin D supplementation, and risk factors for developing MS. Qualitative and semi-quantitative feedback and other data were collected from event questionnaires and a follow-up online survey. ResultsIn total, 86 DS events have been delivered internationally, reaching approximately 345 families affected by MS. Confidence ratings around discussing MS improved in 57/77 families (74%; 95% CI: 62.6–83.1) following a DS event. 39/87 (45%) families who attended DS events reported taking vitamin D prior to the event, and 48/87 (55%) were not supplementing. Of those not taking vitamin D supplements, 71% now take vitamin D supplements, 6% have not changed their behaviour, and the remainder were unsure. ConclusionEducational activities that explain complex neurological diseases to children can be developed and successfully implemented at an international level. These activities give families the confidence to discuss the impact of MS on their lives and also have the potential to change health-related behaviour. Implications for practiceCreative approaches to health behaviour communication can inform children of parents with MS and may affect their behaviour with the aim of potentially reducing their risk of developing MS in the future. Now more than ever, we need educational resources that can facilitate conversations within families that can respond to health information needs in a timely manner.

Neural mass modeling of slow-fast dynamics of seizure initiation and abortion.

Epilepsy is a dynamic and complex neurological disease affecting about 1% of the worldwide population, among which 30% of the patients are drug-resistant. Epilepsy is characterized by recurrent episodes of paroxysmal neural discharges (the so-called seizures), which manifest themselves through a large-amplitude rhythmic activity observed in depth-EEG recordings, in particular in local field potentials (LFPs). The signature characterizing the transition to seizures involves complex oscillatory patterns, which could serve as a marker to prevent seizure initiation by triggering appropriate therapeutic neurostimulation methods. To investigate such protocols, neurophysiological lumped-parameter models at the mesoscopic scale, namely neural mass models, are powerful tools that not only mimic the LFP signals but also give insights on the neural mechanisms related to different stages of seizures. Here, we analyze the multiple time-scale dynamics of a neural mass model and explain the underlying structure of the complex oscillations observed before seizure initiation. We investigate population-specific effects of the stimulation and the dependence of stimulation parameters on synaptic timescales. In particular, we show that intermediate stimulation frequencies (>20 Hz) can abort seizures if the timescale difference is pronounced. Those results have the potential in the design of therapeutic brain stimulation protocols based on the neurophysiological properties of tissue.

Identification of a β-Arrestin 2 Mutation Related to Autism by Whole-Exome Sequencing.

Autism spectrum disorder (ASD) is a complex neurological disease characterized by impaired social communication and interaction skills, rigid behavior, decreased interest, and repetitive activities. The disease has a high degree of genetic heterogeneity, and the genetic cause of ASD in many autistic individuals is currently unclear. In this study, we report a patient with ASD whose clinical features included social interaction disorder, communication disorder, and repetitive behavior. We examined the patient's genetic variation using whole-exome sequencing technology and found new de novo mutations. After analysis and evaluation, ARRB2 was identified as a candidate gene. To study the potential contribution of the ARRB2 gene to the human brain development and function, we first evaluated the expression profile of this gene in different brain regions and developmental stages. Then, we used weighted gene coexpression network analysis to analyze the associations between ARRB2 and ASD risk genes. Additionally, the spatial conformation and stability of the ARRB2 wild type and mutant proteins were examined by simulations. Then, we further established a mouse model of ASD. The results showed abnormal ARRB2 expression in the mouse ASD model. Our study showed that ARRB2 may be a risk gene for ASD, but the contribution of de novo ARRB2 mutations to ASD is unclear. This information will provide references for the etiology of ASD and aid in the mechanism-based drug development and treatment.

Oral health in children with cerebral palsy: A pediatric neurologist’s perspective

Cerebral palsy, one of the most common causes of physical disability in children, is a group of complex neurological disorders caused by non-progressive injury to the developing brain which leads to abnormalities of movement and posture. Dental surgeons must be aware of common practical neurological problems encountered by these children on a day-to-day basis. Awareness of the various factors and strategies mentioned in the article will not only have a major impact on the child’s oral health but also on the quality of life of these children and their families.