Format

Send to

Choose Destination
Nat Commun. 2018 Nov 9;9(1):4724. doi: 10.1038/s41467-018-07113-0.

Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy.

Author information

1
Glial Biology in Health, Disease, and Cancer Center, Virginia Tech Carilion Research Institute, 2 Riverside Cir., Roanoke, VA, 24016, USA.
2
Department of Animal and Poultry Sciences, Virginia Tech, 3460 Litton Reaves Hall, Blacksburg, VA, 24061, USA.
3
Virginia Tech Carilion School of Medicine and Research Institute, 2 Riverside Cir., Roanoke, VA, 24016, USA.
4
Glial Biology in Health, Disease, and Cancer Center, Virginia Tech Carilion Research Institute, 2 Riverside Cir., Roanoke, VA, 24016, USA. sontheim@vt.edu.
5
School of Neuroscience, College of Science, Virginia Tech, 300 Turner Street NW, Blacksburg, VA, 24061, USA. sontheim@vt.edu.

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.

PMID:
30413686
PMCID:
PMC6226462
DOI:
10.1038/s41467-018-07113-0
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center