Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis
| Autor: | Adrian C Thompson, Eric J. James, Jenn J. Park, Andrea Berghella, Carlos D. Aizenman, Lin-Chien Huang, Hollis T. Cline, Sayali Gore |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
matrix metalloproteinase QH301-705.5 Science Xenopus Neurogenesis autism Matrix metalloproteinase MMP9 Nervous System General Biochemistry Genetics and Molecular Biology Extracellular matrix 03 medical and health sciences Xenopus laevis 0302 clinical medicine Seizures medicine Premovement neuronal activity Animals Humans Biology (General) Neurons Valproic Acid General Immunology and Microbiology biology General Neuroscience General Medicine biology.organism_classification Teratology 030104 developmental biology Matrix Metalloproteinase 9 Neurodevelopmental Disorders visual development plasticity Medicine Developmental plasticity lipids (amino acids peptides and proteins) Neuroscience 030217 neurology & neurosurgery medicine.drug Research Article |
| Zdroj: | eLife eLife, Vol 10 (2021) |
| ISSN: | 2050-084X |
| Popis: | Matrix metalloproteinase-9 (MMP-9) is a secreted endopeptidase targeting extracellular matrix proteins, creating permissive environments for neuronal development and plasticity. Developmental dysregulation of MMP-9 may also lead to neurodevelopmental disorders (ND). Here, we test the hypothesis that chronically elevated MMP-9 activity during early neurodevelopment is responsible for neural circuit hyperconnectivity observed in Xenopus tadpoles after early exposure to valproic acid (VPA), a known teratogen associated with ND in humans. In Xenopus tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development. |
| Databáze: | OpenAIRE |
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