The molecular and cellular mechanisms by which alcohol produces its deleterious effects on neuronal networks are only now beginning to be understood. This review focused on alcohol-induced neurobiological alterations ...The molecular and cellular mechanisms by which alcohol produces its deleterious effects on neuronal networks are only now beginning to be understood. This review focused on alcohol-induced neurobiological alterations on neuronal network components underlying information processing, for further understanding of intellectual disability related to FASD. Abnormal neurodevelopmental events related to alcohol-damaged fetal brain included neurogenesis inhibition, aberrant migration, impaired differentiation, exacerbated apoptosis, impaired axon outgrowth and branching altering synaptogenesis and synaptic plasticity, abnormal GABAergic interneurons triggering synaptic inhibitory/excitatory imbalance, reduced myelinogenesis causing injured white matter in prefrontal lobe and atrophied corpus callosum compromising interhemispheric information transfer, the whole compromising neuronal network scaffolding which may lead to biased information processing with deficits in executive function. What added to these abnormalities are smaller gray matter and reduced hippocampus, resulting in cognition and memory failures. As a whole, these developmental disorders may underlie intellectual disability related to FASD. In rodents, these neuronal network components matured mainly during the second and third trimesters equivalents of human gestation. Transferability of results from animal to human was also discussed. It was hoped that the understanding of alcohol-induced neuronal networks failure mechanisms during the developing brain may lay a foundation for prospective new treatments and interventions.展开更多
Neurons are polarized cells with a complex and unique morphology.Each specific type of neuron has distinct functional organelles and protein compositions.This compartmental complexity relies on adaptor protein(AP)comp...Neurons are polarized cells with a complex and unique morphology.Each specific type of neuron has distinct functional organelles and protein compositions.This compartmental complexity relies on adaptor protein(AP)complexes transporting intracellular components to target locations.Malfunctions in the AP complexes can result in a range of abnormalities in neurons that affect neuronal migration,axogenesis,dendritogenesis,neuronal protection,and neural differentiation.These abnormalities also have crucial consequences for the proper functioning of the nervous system.In this article,we review the neuronal functions of AP complexes and provide a comprehensive overview of their links to neurological diseases.展开更多
文摘The molecular and cellular mechanisms by which alcohol produces its deleterious effects on neuronal networks are only now beginning to be understood. This review focused on alcohol-induced neurobiological alterations on neuronal network components underlying information processing, for further understanding of intellectual disability related to FASD. Abnormal neurodevelopmental events related to alcohol-damaged fetal brain included neurogenesis inhibition, aberrant migration, impaired differentiation, exacerbated apoptosis, impaired axon outgrowth and branching altering synaptogenesis and synaptic plasticity, abnormal GABAergic interneurons triggering synaptic inhibitory/excitatory imbalance, reduced myelinogenesis causing injured white matter in prefrontal lobe and atrophied corpus callosum compromising interhemispheric information transfer, the whole compromising neuronal network scaffolding which may lead to biased information processing with deficits in executive function. What added to these abnormalities are smaller gray matter and reduced hippocampus, resulting in cognition and memory failures. As a whole, these developmental disorders may underlie intellectual disability related to FASD. In rodents, these neuronal network components matured mainly during the second and third trimesters equivalents of human gestation. Transferability of results from animal to human was also discussed. It was hoped that the understanding of alcohol-induced neuronal networks failure mechanisms during the developing brain may lay a foundation for prospective new treatments and interventions.
基金supported by the Shanghai Municipal Commission of Science and Technology Research Project(19JC1411001)the National Key Research and Development Program from the Ministry of Science and Technology of the People’s Republic of China(2021YFC2700800)+2 种基金the National Natural Science Foundation of China(31972880,32170615,31371274,and U21A20347)the National Key Research and Development Plan for Stem Cell and Transformation Research(2017YFA0104202)the Collaborative Innovation Center Project Construction for Shanghai Women and Children’s Health.
文摘Neurons are polarized cells with a complex and unique morphology.Each specific type of neuron has distinct functional organelles and protein compositions.This compartmental complexity relies on adaptor protein(AP)complexes transporting intracellular components to target locations.Malfunctions in the AP complexes can result in a range of abnormalities in neurons that affect neuronal migration,axogenesis,dendritogenesis,neuronal protection,and neural differentiation.These abnormalities also have crucial consequences for the proper functioning of the nervous system.In this article,we review the neuronal functions of AP complexes and provide a comprehensive overview of their links to neurological diseases.
