Primary cilia safeguard cortical neurons in neonatal mouse forebrain from environmental stress-induced dendritic degeneration
| Autor: | Toru Sasaki, Masaaki Torii, Nobuyuki Ishibashi, Seiji Ishii, Shahid Mohammad, Edwin Tomy, Hye Hwang, Kazue Hashimoto-Torii, Hideyuki Okano, Fahad Somaa, Pasko Rakic |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Cell Biology Mice Prosencephalon Neural Stem Cells Pregnancy medicine Animals Cilia Insulin-Like Growth Factor I Cytoskeleton Receptor Protein kinase B Neurons Multidisciplinary Perinatal Exposure Growth factor Cilium Brain Dendrites Biological Sciences Cell biology Mice Inbred C57BL medicine.anatomical_structure Animals Newborn Prenatal Exposure Delayed Effects Forebrain Female Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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