Primary cilia safeguard cortical neurons in neonatal mouse forebrain from environmental stress-induced dendritic degeneration
Year: 2020
Type: article
Abstract: The developing brain is under the risk of exposure to a multitude of environmental stressors. While perinatal exposure to excessive levels of environmental stress is responsible for a wide spectrum of neurological and psychiatric conditions, the developing brain is equipped with intrinsic cell protection, the mechanisms of which remain unknown. Here we show, using neonatal mouse as a model system, that primary cilia, hair-like protrusions from the neuronal cell body, play an essential role in protecting immature neurons from the negative impacts of exposure to environmental stress. More specifically, we found that primary cilia prevent the degeneration of dendritic arbors upon exposure to alcohol and ketamine, two major cell stressors, by activating cilia-localized insulin-like growth factor 1 receptor and downstream Akt signaling. We also found that activation of this pathway inhibits Caspase-3 activation and caspase-mediated cleavage/fragmentation of cytoskeletal proteins in stress-exposed neurons. These results indicate that primary cilia play an integral role in mitigating adverse impacts of environmental stressors such as drugs on perinatal brain development.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Ministry of Education, Culture, Sports, Science and Technology, Japan Society for the Promotion of Science, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G176129931, White Matter Protection in the Fetus with Congenital Heart Disease, Analysis of environmental stress response downstream cascade in cerebral cortex formation, District of Columbia Intellectual and Developmental Disabilities Research Center, G4476980562, G4695824253, G4731300183, The roles of alcohol-inducible RNA-operons in the fetal brain, G4809771986, Roles of Primary Cilia in the Developing Cortex Exposed to Alcohol, Significance and molecular mechanisms of primary cilia controlling the stress critical period of cortical development., Mechanisms and treatments of learning deficits in Fetal Alcohol Spectrum Disorders, G7073685522, Role of autism-linked genes in developmental refinement of the corpus callosum, Origin of Cortical Species-specific Distinctions., G8569187252, G8601401583, G8746722232, Cell Therapy for Neuroprotection in Congenital Heart Disease, Origin of Cortical Species-specific Distinctions
OpenAlex ID: W3114094797