Increased expression of caspase 2 in experimental and human temporal lobe epilepsy.
Temporal lobe epilepsy (TLE) is often caused by a neurodegenerative brain insult that triggers epileptogenesis, and eventually results in spontaneous seizures, i.e., epilepsy. Understanding the mechanisms of cell death is a key for designing new drug therapies for preventing the neurodegeneration associated with TLE. Here, we investigated the expression of caspase 2, a protein involved in programmed cell death, during the course of epilepsy. We investigated caspase 2 expression in hippocampal samples derived from patients operated on for drug refractory TLE. To understand the evolution of altered-caspase 2 expression during the epileptic process, we also examined caspase 2 expression and activity in the rat hippocampus after status epilepticus-induced acute damage, during epileptogenesis, and after the onset of epilepsy. Caspase 2 expression was enhanced in the hippocampal neurons in chronic TLE patients. In rats, status epilepticus-induced caspase 2 labeling paralleled the progression of neurodegeneration. Proteolytic activation and cleavage of caspase 2 was also detected in the rat brain undergoing epileptogenesis. Our data suggest that caspase 2-mediated programmed cell death participates in the seizure-induced degenerative process in experimental and human TLE.
Narkilahti
Susanna
S
A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, and Department of Neurology, Kuopio University Hospital, Finland. susanna.narkilahti@regea.fi
Jutila
Leena
L
Alafuzoff
Irina
I
Karkola
Kari
K
Paljärvi
Leo
L
Immonen
Arto
A
Vapalahti
Matti
M
Mervaala
Esa
E
Kälviäinen
Reetta
R
Pitkänen
Asla
A
D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053143:Caspase 2 / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology* / Q000473:pathology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced
D018690:Excitatory Amino Acid Agonists; D053143:Caspase 2; D007608:Kainic Acid