scholarly journals Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders

2021 ◽  
Vol 22 (17) ◽  
pp. 9503
Author(s):  
Juan Prieto-Villalobos ◽  
Tanhia F. Alvear ◽  
Andrés Liberona ◽  
Claudia M. Lucero ◽  
Claudio J. Martínez-Araya ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Neuronal Damage ◽  
Redox Homeostasis ◽  
Harmful Effect ◽  
Brain Dysfunction ◽  
Autism Spectrum ◽  
Maternal Inflammation ◽  
Brain Structure And Function ◽  
Prenatal Inflammation ◽  
And Function

Maternal inflammation during pregnancy causes later-in-life alterations of the offspring’s brain structure and function. These abnormalities increase the risk of developing several psychiatric and neurological disorders, including schizophrenia, intellectual disability, bipolar disorder, autism spectrum disorder, microcephaly, and cerebral palsy. Here, we discuss how astrocytes might contribute to postnatal brain dysfunction following maternal inflammation, focusing on the signaling mediated by two families of plasma membrane channels: hemi-channels and pannexons. [Ca2+]i imbalance linked to the opening of astrocytic hemichannels and pannexons could disturb essential functions that sustain astrocytic survival and astrocyte-to-neuron support, including energy and redox homeostasis, uptake of K+ and glutamate, and the delivery of neurotrophic factors and energy-rich metabolites. Both phenomena could make neurons more susceptible to the harmful effect of prenatal inflammation and the experience of a second immune challenge during adulthood. On the other hand, maternal inflammation could cause excitotoxicity by producing the release of high amounts of gliotransmitters via astrocytic hemichannels/pannexons, eliciting further neuronal damage. Understanding how hemichannels and pannexons participate in maternal inflammation-induced brain abnormalities could be critical for developing pharmacological therapies against neurological disorders observed in the offspring.

scholarly journals Towards Neurosubtypes in Autism

2019 ◽  
Author(s):  
Seok-Jun Hong ◽  
Joshua Tzvi Vogelstein ◽  
Alessandro gozzi ◽  
Boris C. Bernhardt ◽  
B.T. Thomas Yeo ◽  
...  
Keyword(s):  
Autism Spectrum ◽  
Current Data ◽  
System Level ◽  
Diagnostic Labels ◽  
Study Results ◽  
Brain Structure And Function ◽  
Diagnostic Samples ◽  
And Function ◽  
Substantial Heterogeneity ◽  
Selection Of

There is a general consensus that substantial heterogeneity underlies the neurobiology in autism spectrum disorder (ASD). As such, it has become increasingly clear that a dissection of variation at the molecular-, cellular-, and system-level domains is a prerequisite for identifying biomarkers and developing more targeted therapeutic strategies in ASD. Advances in neuroimaging approaches to characterizing atypical brain patterns have recently motivated their application as viable tools to delineate more homogenous ASD subgroups at the level of brain structure and function - i.e., neurosubtyping. This review assesses and critically discusses the current data-driven neurosubtyping in ASD. It breaks this pursuit into key methodological steps: the selection of diagnostic samples, neuroimaging features, algorithm and validation approaches. For each step, we appraise the current literature in terms of progress, as well as remaining challenges and potential solutions. Convergence across findings is discussed and biological implications are highlighted. Although preliminary and with limited methodological overlap, results from this literature illustrate the feasibility of neurosubtyping. Across studies, there is general agreement that distinct neurosubtypes exist, but the exact number and their definitions vary depending on the specific features and approach utilized in a given study. Results also suggest the utility of subtypes in predicting symptom severity and diagnostic labels above and beyond group-average comparison designs. This review concludes with a discussion of future avenues towards a comprehensive understanding of the mechanisms underlying ASD heterogeneity.

scholarly journals Microglia and astrocyte involvement in neurodegeneration and brain cancer

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Arthur A. Vandenbark ◽  
Halina Offner ◽  
Szymon Matejuk ◽  
Agata Matejuk
Keyword(s):  
Neurological Disorders ◽  
Neurological Diseases ◽  
The Body ◽  
Normal Brain ◽  
Key Factors ◽  
Therapeutic Outcomes ◽  
Brain Structure And Function ◽  
And Function ◽  
Different Origins ◽  
Frontotemporal Lobar Dementia

AbstractThe brain is unique and the most complex organ of the body, containing neurons and several types of glial cells of different origins and properties that protect and ensure normal brain structure and function. Neurological disorders are the result of a failure of the nervous system multifaceted cellular networks. Although great progress has been made in the understanding of glia involvement in neuropathology, therapeutic outcomes are still not satisfactory. Here, we discuss recent perspectives on the role of microglia and astrocytes in neurological disorders, including the two most common neurodegenerative conditions, Alzheimer disease and progranulin-related frontotemporal lobar dementia, as well as astrocytoma brain tumors. We emphasize key factors of microglia and astrocytic biology such as the highly heterogeneic glial nature strongly dependent on the environment, genetic factors that predispose to certain pathologies and glia senescence that inevitably changes the CNS landscape. Our understanding of diverse glial contributions to neurological diseases can lead advances in glial biology and their functional recovery after CNS malfunction.

scholarly journals Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

2020 ◽  
Vol 21 (16) ◽  
pp. 5850 ◽  
Author(s):  
Sabrina I. Hanswijk ◽  
Marcia Spoelder ◽  
Ling Shan ◽  
Michel M. M. Verheij ◽  
Otto G. Muilwijk ◽  
...  
Keyword(s):  
Brain Development ◽  
Animal Studies ◽  
Fetal Brain ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
Hyperactivity Disorder ◽  
Maternal Genotype ◽  
Brain Structure And Function ◽  
And Function ◽  
And Behavior

Serotonin (5-HT) is a critical player in brain development and neuropsychiatric disorders. Fetal 5-HT levels can be influenced by several gestational factors, such as maternal genotype, diet, stress, medication, and immune activation. In this review, addressing both human and animal studies, we discuss how these gestational factors affect placental and fetal brain 5-HT levels, leading to changes in brain structure and function and behavior. We conclude that gestational factors are able to interact and thereby amplify or counteract each other’s impact on the fetal 5-HT-ergic system. We, therefore, argue that beyond the understanding of how single gestational factors affect 5-HT-ergic brain development and behavior in offspring, it is critical to elucidate the consequences of interacting factors. Moreover, we describe how each gestational factor is able to alter the 5-HT-ergic influence on the thalamocortical- and prefrontal-limbic circuitry and the hypothalamo-pituitary-adrenocortical-axis. These alterations have been associated with risks to develop attention deficit hyperactivity disorder, autism spectrum disorders, depression, and/or anxiety. Consequently, the manipulation of gestational factors may be used to combat pregnancy-related risks for neuropsychiatric disorders.

scholarly journals The Involvement of Neuron-Specific Factors in Dendritic Spinogenesis: Molecular Regulation and Association with Neurological Disorders

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hsiao-Tang Hu ◽  
Pu-Yun Shih ◽  
Yu-Tzu Shih ◽  
Yi-Ping Hsueh
Keyword(s):  
Actin Cytoskeleton ◽  
Dendritic Spine ◽  
Neurological Disorders ◽  
Synapse Formation ◽  
Adaptor Proteins ◽  
Autism Spectrum ◽  
Specific Gene ◽  
Excitatory Synapses ◽  
Specific Factors ◽  
And Function

Dendritic spines are the location of excitatory synapses in the mammalian nervous system and are neuron-specific subcellular structures essential for neural circuitry and function. Dendritic spine morphology is determined by the F-actin cytoskeleton. F-actin remodeling must coordinate with different stages of dendritic spinogenesis, starting from dendritic filopodia formation to the filopodia-spines transition and dendritic spine maturation and maintenance. Hundreds of genes, including F-actin cytoskeleton regulators, membrane proteins, adaptor proteins, and signaling molecules, are known to be involved in regulating synapse formation. Many of these genes are not neuron-specific, but how they specifically control dendritic spine formation in neurons is an intriguing question. Here, we summarize how ubiquitously expressed genes, including syndecan-2, NF1 (encoding neurofibromin protein), VCP, and CASK, and the neuron-specific gene CTTNBP2 coordinate with neurotransmission, transsynaptic signaling, and cytoskeleton rearrangement to control dendritic filopodia formation, filopodia-spines transition, and dendritic spine maturation and maintenance. The aforementioned genes have been associated with neurological disorders, such as autism spectrum disorders (ASDs), mental retardation, learning difficulty, and frontotemporal dementia. We also summarize the corresponding disorders in this report.

scholarly journals Repetitive Mild Head Trauma Induces Activity-Mediated Lifelong Brain Deficits in a Novel Drosophila Model

2021 ◽  
Author(s):  
Joseph A. Behnke ◽  
Changtian Ye ◽  
Aayush Setty ◽  
Kenneth H. Moberg ◽  
James Q. Zheng
Keyword(s):  
Head Trauma ◽  
Neuronal Excitability ◽  
Brain Dysfunction ◽  
Suitable Model ◽  
Long Term Effects ◽  
Head Impacts ◽  
Brain Structure And Function ◽  
Underlying Mechanisms ◽  
And Function

AbstractMild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Here, we developed a novel head impact system to investigate the long-term effects of mild head trauma on brain structure and function, as well as the underlying mechanisms in Drosophila melanogaster. We find that Drosophila subjected to repetitive head impacts develop long-term deficits, including impaired startle-induced climbing, progressive brain degeneration, and shortened lifespan, all of which are substantially exacerbated in female flies. Interestingly, head impacts elicit an elevation in neuronal activity and its acute suppression abrogates the detrimental effects in female flies. Together, our findings validate Drosophila as a suitable model system for investigating the long-term effects of mild head trauma, suggest an increased vulnerability in brain injury in female flies, and indicate that early altered neuronal excitability may be a key mechanism linking mild brain trauma to chronic degeneration.

Attention Deficit Hyperactivity Disorder

2021 ◽  
pp. 59-94
Author(s):  
Eric Taylor
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Stimulant Medication ◽  
Autism Spectrum ◽  
Hyperactivity Disorder ◽  
Cognitive Limitations ◽  
Time Treatment ◽  
Brain Structure And Function ◽  
Considerable Controversy ◽  
And Function

This chapter describes the recognition and associations of the syndrome of attention deficit hyperactivity disorder (ADHD), with special reference to the multitude of associated problems. Inattentiveness, overactivity, and impulsiveness are behaviour styles that predict later disadvantage in education, employment, physical health, substance use, mental health, and personal relationships. They very often coexist with features of oppositional disorders, anxiety, and the autism spectrum. These are considered both as differential diagnoses and as multiple morbidities needing to be recognized. Several cognitive limitations, including in executive function, can be identified by psychological testing. Genetic inheritance is a powerful influence. Neuroimaging is detecting an increasing number of changes in brain structure and function. The problems are widespread, but recognition of the syndrome varies between countries. The diagnosis is increasing in frequency over time. Treatment with stimulant medication is often helpful, but there is considerable controversy about how widely to apply it.

scholarly journals Could Perinatal Asphyxia Induce a Synaptopathy? New Highlights from an Experimental Model

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
María Inés Herrera ◽  
Matilde Otero-Losada ◽  
Lucas Daniel Udovin ◽  
Carlos Kusnier ◽  
Rodolfo Kölliker-Frers ◽  
...  
Keyword(s):  
Experimental Model ◽  
Neural Development ◽  
Neurological Disorders ◽  
Perinatal Asphyxia ◽  
Birth Asphyxia ◽  
Synaptic Connectivity ◽  
Synaptic Dysfunction ◽  
Preterm Neonates ◽  
Brain Structure And Function ◽  
And Function

Birth asphyxia also termed perinatal asphyxia is an obstetric complication that strongly affects brain structure and function. Central nervous system is highly susceptible to oxidative damage caused by perinatal asphyxia while activation and maturity of the proper pathways are relevant to avoiding abnormal neural development. Perinatal asphyxia is associated with high morbimortality in term and preterm neonates. Although several studies have demonstrated a variety of biochemical and molecular pathways involved in perinatal asphyxia physiopathology, little is known about the synaptic alterations induced by perinatal asphyxia. Nearly 25% of the newborns who survive perinatal asphyxia develop neurological disorders such as cerebral palsy and certain neurodevelopmental and learning disabilities where synaptic connectivity disturbances may be involved. Accordingly, here we review and discuss the association of possible synaptic dysfunction with perinatal asphyxia on the basis of updated evidence from an experimental model.

Development of Neural Structure and Function in Autism Spectrum Disorder: Potential Implications for Learning Language

2020 ◽  
Vol 29 (4) ◽  
pp. 1783-1797
Author(s):  
Kelly L. Coburn ◽  
Diane L. Williams
Keyword(s):  
Autism Spectrum Disorder ◽  
Language Development ◽  
Diffusion Tensor ◽  
Autism Spectrum ◽  
Language Intervention ◽  
Spectrum Disorder ◽  
Autistic Children ◽  
Neural Structure ◽  
Complex Information ◽  
And Function

Purpose Neurodevelopmental processes that begin during gestation and continue throughout childhood typically support language development. Understanding these processes can help us to understand the disruptions to language that occur in neurodevelopmental conditions, such as autism spectrum disorder (ASD). Method For this tutorial, we conducted a focused literature review on typical postnatal brain development and structural and functional magnetic resonance imaging, diffusion tensor imaging, magnetoencephalography, and electroencephalography studies of the neurodevelopmental differences that occur in ASD. We then integrated this knowledge with the literature on evidence-based speech-language intervention practices for autistic children. Results In ASD, structural differences include altered patterns of cortical growth and myelination. Functional differences occur at all brain levels, from lateralization of cortical functions to the rhythmic activations of single neurons. Neuronal oscillations, in particular, could help explain disrupted language development by elucidating the timing differences that contribute to altered functional connectivity, complex information processing, and speech parsing. Findings related to implicit statistical learning, explicit task learning, multisensory integration, and reinforcement in ASD are also discussed. Conclusions Consideration of the neural differences in autistic children provides additional scientific support for current recommended language intervention practices. Recommendations consistent with these neurological findings include the use of short, simple utterances; repetition of syntactic structures using varied vocabulary; pause time; visual supports; and individualized sensory modifications.

Sign in / Sign up

Export Citation Format

Share Document