Zebrafish Minichromosome Maintenance Protein 5 Gene Regulates the Development and Migration of Facial Motor Neurons via Fibroblast Growth Factor Signaling
Minichromosome maintenance protein 5 (MCM5), a member of the microchromosomal maintenance protein family, plays an important role in the initiation and extension of DNA replication. However, its role in neural development in zebrafish remains unclear. Here, we used morpholino (MO) and CRISPR/Cas9 to knock downmcm5 and investigated the developmental features of facial motor neurons (FMNs) in the hindbrain of zebrafish. We found that knockdown ofmcm5 usingmcm5 MO resulted in a small head, small eyes, and a blurred midbrain-hindbrain boundary, while MO injection ofmcm5 led to decrease in FMNs and their migration disorder. How...
Source: Developmental Neuroscience - June 15, 2021 Category: Neuroscience Source Type: research
Galectin-3 modulates microglia inflammation in vitro but not neonatal brain injury in vivo under inflammatory conditions
(Source: Developmental Neuroscience)
Source: Developmental Neuroscience - June 15, 2021 Category: Neuroscience Source Type: research
Maternal Interleukin-6 Hampers Hippocampal Neurogenesis in Adult Rat Offspring in a Sex-Dependent Manner
The objective of this study was to assess whether this naturally occurring IL-6 has long-lasting effects on brain plasticity and function. Therefore, pregnant rats were given either an IL-6-neutralizing antibody (IL-6Ab) or vehicle during the third week of pregnancy. Newly born (doublecortin) and mature neurons (NeuN) were monitored in the hippocampus of adult male and female offspring. Prenatal IL-6Ab led to an enhanced number of newly born and mature neurons in the dentate gyrus of the hippocampus of male but not female adult offspring. This enhanced neurogenesis was associated with an increased propensity in memory acqu...
Source: Developmental Neuroscience - May 21, 2021 Category: Neuroscience Source Type: research
The Dopamine Hypothesis of Autism Spectrum Disorder Revisited: Current Status and Future Prospects
Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. Despite intensive research, its etiopathogenesis remains largely unclear. Although studies consistently reported dopaminergic anomalies, a coherent dopaminergic model of ASD was lacking until recently. In 2017, we provided a theoretical framework for a “dopamine hypothesis of ASD” which proposed that autistic behavior arises from a dysfunctional midbrain dopaminergic system. Namely, we hypothesized that malfunction of 2 critical circuits originating in the midbrain, that is, the m...
Source: Developmental Neuroscience - May 19, 2021 Category: Neuroscience Source Type: research
Enhancing Translational Developmental Cognitive Neuroscience with Advanced Neuroimaging Analyses
Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - May 12, 2021 Category: Neuroscience Source Type: research
Targeting Poison Exons to Treat Developmental and Epileptic Encephalopathy
Developmental and epileptic encephalopathies (DEEs) describe a subset of neurodevelopmental disorders categorized by refractory epilepsy that is often associated with intellectual disability and autism spectrum disorder. The majority of DEEs are now known to have a genetic basis with de novo coding variants accounting for the majority of cases. More recently, a small number of individuals have been identified with intronicSCN1A variants that result in alternative splicing events that lead to ectopic inclusion of poison exons (PEs). PEs are short highly conserved exons that contain a premature truncation codon, and when spl...
Source: Developmental Neuroscience - May 10, 2021 Category: Neuroscience Source Type: research
CRISPR/dCas9 as a Therapeutic Approach for Neurodevelopmental Disorders: Innovations and Limitations Compared to Traditional Strategies
Brain development is a complex process that requires a series of precise and coordinated events to take place. When alterations in some of those events occur, neurodevelopmental disorders (NDDs) may appear, with their characteristic symptoms, including cognitive, social motor deficits, and epilepsy. While pharmacologic treatments have been the only therapeutic options for many years, more recently the research is turning to the direct removal of the underlying genetic cause of each specific NDD. This is possible thanks to the increased knowledge of genetic basis of those diseases and the enormous advances in genome-editing...
Source: Developmental Neuroscience - May 3, 2021 Category: Neuroscience Source Type: research
Adverse Maternal Environment Alters MicroRNA-10b-5p Expression and Its Epigenetic Profile Concurrently with Impaired Hippocampal Neurogenesis in Male Mouse Hippocampus
An adverse maternal environment (AME) predisposes adult offspring toward cognitive impairment in humans and mice. However, the underlying mechanisms remain poorly understood. Epigenetic changes in response to environmental exposure may be critical drivers of this change. Epigenetic regulators, including microRNAs, have been shown to affect cognitive function by altering hippocampal neurogenesis which is regulated in part by brain-derived neurotropic factor (BDNF). We sought to investigate the effects of AME on miR profile and their epigenetic characteristics, as well as neurogenesis and BDNF expression in mouse hippocampus...
Source: Developmental Neuroscience - May 3, 2021 Category: Neuroscience Source Type: research
Current Approaches and Future Directions for the Treatment of mTORopathies
The mechanistic target of rapamycin (mTOR) is a kinase at the center of an evolutionarily conserved signaling pathway that orchestrates cell growth and metabolism. mTOR responds to an array of intra- and extracellular stimuli and in turn controls multiple cellular anabolic and catabolic processes. Aberrant mTOR activity is associated with numerous diseases, with particularly profound impact on the nervous system. mTOR is found in two protein complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which are governed by different upstream regulators and have distinct cellular actions. Mutations in genes encoding for mTOR regulato...
Source: Developmental Neuroscience - April 28, 2021 Category: Neuroscience Source Type: research
Gene Transfer Therapy for Neurodevelopmental Disorders
Neurodevelopmental disorders (NDDs) include a broad spectrum of disorders that disrupt normal brain development. Though some NDDs are caused by acquired insults (i.e., toxic or infectious encephalopathy) or may be cryptogenic, many NDDs are caused by variants in a single gene or groups of genes that disrupt neuronal development or function. In this review, we will focus on those NDDs with a genetic etiology. The exact mechanism, timing, and progression of the molecular pathology are seldom well known; however, the abnormalities in development typically manifest in similar patterns such as delays or regression in motor func...
Source: Developmental Neuroscience - April 21, 2021 Category: Neuroscience Source Type: research
Repetitive Mild Traumatic Brain Injury in a Perinatal Nicotine Exposure Mouse Model of Attention Deficit Hyperactivity Disorder
Attention deficit hyperactivity disorder (ADHD) increases the risk for concussion or mild traumatic brain injury (mTBI). At the same time, recommendations for the management of ADHD include participation in sports and other organized physical activities, including those that carry an increased risk of mTBI. Very little work has been done to determine the extent to which untreated ADHD adversely impacts behavioral outcomes of repeated mild concussions. Here, we used a perinatal nicotine exposure (PNE) mouse model of ADHD combined with a closed-head, repetitive mTBI model. The PNE mouse model carries significant construct, f...
Source: Developmental Neuroscience - April 13, 2021 Category: Neuroscience Source Type: research
Aluminum Microcomb Electrodes on Silicon Wafer for Detecting Val66Met Polymorphism in Brain-Derived Neurotrophic Factor
Conclusion: The above detection strategy will be useful for the detection and quantification of BDNF, thereby aiding in the provision of suitable treatments for BDNF-related disorders.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - April 13, 2021 Category: Neuroscience Source Type: research
Long Noncoding RNA SPRY4-IT1 Modulates Ketamine-Induced Neurotoxicity in Human Embryonic Stem Cell-Derived Neurons through EZH2
Conclusions: SPRY4-IT1 is involved in anesthesia-induced neurotoxicity, possibly through the regulation on EZH2 gene.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - April 7, 2021 Category: Neuroscience Source Type: research
Abnormal Cerebellar Development in Autism Spectrum Disorders
Autism spectrum disorders (ASD) comprise a group of heterogeneous neurodevelopmental conditions characterized by impaired social interactions and repetitive behaviors with symptom onset in early infancy. The genetic risks for ASD have long been appreciated: concordance of ASD diagnosis may be as high as 90% for monozygotic twins and 30% for dizygotic twins, and hundreds of mutations in single genes have been associated with ASD. Nevertheless, only 5 –30% of ASD cases can be explained by a known genetic cause, suggesting that genetics is not the only factor at play. More recently, several studies reported that up to 40% o...
Source: Developmental Neuroscience - April 6, 2021 Category: Neuroscience Source Type: research
A Role for Vasoactive Intestinal Peptide Interneurons in Neurodevelopmental Disorders
GABAergic inhibitory interneurons of the cerebral cortex expressing vasoactive intestinal peptide (VIP-INs) are rapidly emerging as important regulators of network dynamics and normal circuit development. Several recent studies have also identified VIP-IN dysfunction in models of genetically determined neurodevelopmental disorders (NDDs). In this article, we review the known circuit functions of VIP-INs and how they may relate to accumulating evidence implicating VIP-INs in the mechanisms of prominent NDDs. We highlight recurring VIP-IN-mediated circuit motifs that are shared across cerebral cortical areas and how VIP-IN a...
Source: Developmental Neuroscience - April 1, 2021 Category: Neuroscience Source Type: research
