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Parvalbumin interneuron-derived tissue-type plasminogen activator shapes perineuronal net structure.
Matthieu Lépine1, Sara Douceau1, Gabrielle Devienne2
1Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders, Institut Blood and Brain @ Caen Normandie, Cyceron, Bd Becquerel, BP 5229-14074, 14000, Caen, France.
BMC Biology
|October 5, 2022
Summary
Tissue-type plasminogen activator (tPA) released by specific neurons remodels perineuronal nets (PNNs) by degrading key components. This finding reveals a novel mechanism controlling brain plasticity and PNN structure.
Area of Science:
- Neuroscience
- Extracellular Matrix Biology
- Molecular Cell Biology
Background:
- Perineuronal nets (PNNs) are crucial extracellular matrix structures surrounding fast-spiking parvalbumin (FS-PV) interneurons.
- Altered PNNs are implicated in neurodevelopmental disorders and neurodegenerative diseases like Alzheimer's.
- The role of tissue-type plasminogen activator (tPA) in PNN remodeling is unknown.
Purpose of the Study:
- To investigate the cellular source and function of tPA in the brain.
- To determine if tPA influences PNN structure and plasticity.
- To elucidate the molecular mechanisms of tPA-mediated PNN remodeling.
Main Methods:
- GFP reporter mice
- Immunohistology
- Electrophysiology
- Single-cell RT-PCR
- Primary interneuron cultures
Main Results:
- Cortical FS-PV interneurons were identified as a source of tPA in vivo.
- Mice lacking tPA in FS-PV interneurons exhibited denser PNNs.
- In vitro, tPA converted plasminogen to plasmin, which degraded aggrecan, a major PNN proteoglycan.
Conclusions:
- tPA released by FS-PV interneurons reduces PNN density via aggrecan degradation.
- This tPA-dependent PNN remodeling offers new insights into brain plasticity regulation.
