Calpain-2 activation in mouse hippocampus plays a critical role in seizure-induced neuropathology.
Neurobiol Dis
; 147: 105149, 2021 01.
Article
in En
| MEDLINE
| ID: mdl-33132163
ABSTRACT
Calpain has been proposed to play a critical role in the development of epilepsy. Here we used conditional calpain-2 knock-out (C2CKO) mice in a C57/Bl6 background and a selective calpain-2 inhibitor to analyze the role of calpain-2 in epilepsy. Neurodegeneration was evident in various hippocampal subfields, in particular in mossy cells in the hilus of the dentate gyrus (DG) in C57/Bl6 mice 7 days after kainic acid (KA)-induced seizures. Calpain-2 activation was still observed in mossy cells 7 days after seizures. Calpain activation, astroglial and microglial activation, neurodegeneration, and cognitive impairment were absent in C2CKO mice and in C57/Bl6 mice treated with a selective calpain-2 inhibitor for 7 days after seizure initiation. Levels of the potassium chloride cotransporter 2 (KCC2) were decreased in mossy cells 7 days after seizures and this decrease was prevented by calpain-2 deletion or selective inhibition. Our results indicate that prolonged calpain-2 activation plays a critical role in neuropathology following seizures. A selective calpain-2 inhibitor could represent a therapeutic treatment for seizure-induced neuropathology.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calpain
/
Epilepsy
/
Hippocampus
Limits:
Animals
Language:
En
Journal:
Neurobiol Dis
Journal subject:
NEUROLOGIA
Year:
2021
Document type:
Article
Affiliation country:
United States