Back to Search
Start Over
Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis
- Source :
- eLife, eLife, Vol 10 (2021)
- Publication Year :
- 2021
- Publisher :
- eLife Sciences Publications, Ltd, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....00654d22ad75b2ae59cd3ae2c8a35996