Pilocarpine-induced seizures are accompanied by a transient elevation in the messenger RNA expression of the prohormone convertase PC1 in rat hippocampus: comparison with nerve growth factor and brain-derived neurotrophic factor expression.
Several prohormone convertases that are involved in the posttranslational processing of precursor proteins, including neuropetides, hormones and neurotrophic factors, are produced in the central nervous system. These include enzymes named furin, PC1, PC2, PC5 and PACE4. To understand better the potential role played by prohormone convertases in the central nervous system we studied the expression of their messenger RNAs in the hippocampus of rats with pilocarpine-induced seizures. Moreover, we compared their expression patterns with those of neurotrophins such as nerve growth factor and brain-derived neurotrophic factor, which are up-regulated in the hippocampus during seizures. Pilocarpine (380 mg/kg, i.p.) induced seizure activity that appeared within the first hour and persisted for approximately 8 h. In situ hybridization showed transient increases in messenger RNA for nerve growth factor and brain-derived neurotrophic factor that peaked at 120 min in the hippocampus. Among the convertases studied, only PC1 messenger RNA displayed up-regulation, with temporal and topographic features comparable to those of nerve growth factor and brain-derived neurotrophic factor messenger RNA. The expression of furin, PC2 and PC5 messenger RNA changed little, while PACE4 was not expressed at all, both before and after pilocarpine administration. The highest increase in PC1 messenger RNA expression was found in granule cells of the dentate gyrus and, to a lesser extent, in the pyramidal layer of CA1 and CA3 subfields. Thus, in the rat hippocampus, the epileptiform activity induced by pilocarpine mediates a co-ordinated expression of messenger RNAs for PC1, nerve growth factor and brain-derived neurotrophic factor. Our findings suggest the involvement of PC1 in the processing of precursor proteins during seizure activity.
Marcinkiewicz
M
M
J. A. DeSève Laboratory of Molecular Neuroendocrinology, University ofMontreal, Quebec, Canada.
Nagao
T
T
Day
R
R
Seidah
N G
NG
Chrétien
M
M
Avoli
M
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D018679:Cholinergic Agonists / Q000494:pharmacology; D015342:DNA Probes; D004569:Electroencephalography; D045683:Furin; D006624:Hippocampus / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D010862:Pilocarpine / Q000494:pharmacology; D010957:Plasmids; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013381:Subtilisins / Q000096:biosynthesis*
D019208:Brain-Derived Neurotrophic Factor; D018679:Cholinergic Agonists; D015342:DNA Probes; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D010862:Pilocarpine; D013381:Subtilisins; D045683:Furin