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Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy
- Source :
- Epilepsy Currents, Nature Communications, Vol 9, Iss 1, Pp 1-17 (2018), Nature Communications
- Publication Year :
- 2017
-
Abstract
- Brain tumor patients commonly present with epileptic seizures. We show that tumor-associated seizures are the consequence of impaired GABAergic inhibition due to an overall loss of peritumoral fast spiking interneurons (FSNs) concomitant with a significantly reduced firing rate of those that remain. The reduced firing is due to the degradation of perineuronal nets (PNNs) that surround FSNs. We show that PNNs decrease specific membrane capacitance of FSNs permitting them to fire action potentials at supra-physiological frequencies. Tumor-released proteolytic enzymes degrade PNNs, resulting in increased membrane capacitance, reduced firing, and hence decreased GABA release. These studies uncovered a hitherto unknown role of PNNs as an electrostatic insulator that reduces specific membrane capacitance, functionally akin to myelin sheaths around axons, thereby permitting FSNs to exceed physiological firing rates. Disruption of PNNs may similarly account for excitation-inhibition imbalances in other forms of epilepsy and PNN protection through proteolytic inhibition may provide therapeutic benefits.<br />Brain tumours are associated with epilepsy. Here the authors show, using a mouse model, that the degradation of perineuronal nets around fast spiking interneurons near the tumour contribute to seizures by increasing their membrane capacitance and firing.
- Subjects :
- 0301 basic medicine
Male
Science
General Physics and Astronomy
Action Potentials
Mice, Nude
Mice, SCID
Electric Capacitance
Article
General Biochemistry, Genetics and Molecular Biology
Biophysical Phenomena
03 medical and health sciences
Epilepsy
0302 clinical medicine
Interneurons
medicine
Animals
Gliosis
lcsh:Science
Membrane potential
Multidisciplinary
Extramural
Chemistry
Brain Neoplasms
musculoskeletal, neural, and ocular physiology
Perineuronal net
Myelin sheaths
Cell Membrane
Proteolytic enzymes
General Chemistry
Glioma
medicine.disease
Current Literature in Basic Science
Extracellular Matrix
Disease Models, Animal
030104 developmental biology
nervous system
lcsh:Q
Gabaergic inhibition
Female
Neuroscience
030217 neurology & neurosurgery
Peptide Hydrolases
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....074185b2cf97ac928612fe5da7eb7368