Patterns of status epilepticus-induced substance P expression during development.
Substance P, which modulates synaptic excitability, can be induced by a variety of stimuli. We studied the expression of hippocampal substance P in rats in using lithium-pilocarpine model of status epilepticus during development. Status epilepticus resulted in an age-specific manner of substance P expression that was anatomically distinctive in hippocampal subfields. Maximal induction of substance P immunoreactivity was seen in the CA1 region of the two-week-old rats, and progressively decreased in the three-, four-week-old rats and adults. Meanwhile, the number of substance P-immunoreactive neurons in the CA3 region and dentate granule cell layer was minimal in the two-week-old animals, but approximated the adult level in the three- and four-week-old rats. No substance P-immunoreactive axon terminals were seen in the strata pyramidale and lucidum in the CA3 region of the two-week-old rats, but they were found to progressively increase in the three-, four-week-old rats and adults. To confirm substance P expression after status epilepticus, we studied the expression of preprotachykinin-A mRNA in the hippocampus of the three-week-old rats by in situ hybridization. Two hours following injection of lithium-pilocarpine, preprotachykinin-A mRNA dramatically increased in the granule cells, as well as in the CA3 and CA1 pyramidal cell layers of the hippocampus. To evaluate the relationship between behavioral seizures and substance P induction, we used the NMDA receptor antagonist MK-801. Injection of MK-801 completely blocked lithium-pilocarpine-induced behavioral seizures and SP induction in the two-week-old rats. These results indicate that seizure activity selectively evokes age-dependent and region-selective expression of substance P.
Liu
H
H
Epilepsy Research Laboratory, Veteran Administration Medical Center, Sepulveda, CA 91343, USA. htliu@ucla.edu
Sankar
R
R
Shin
D H
DH
Mazarati
A M
AM
Wasterlain
C G
CG
D000367:Age Factors; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D018021:Lithium Chloride / Q000009:adverse effects; D008297:Male; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010862:Pilocarpine / Q000009:adverse effects; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013373:Substance P / Q000378:metabolism*; D015320:Tachykinins / Q000378:metabolism
D011498:Protein Precursors; D016194:Receptors, N-Methyl-D-Aspartate; D015320:Tachykinins; C044206:preprotachykinin; D010862:Pilocarpine; D013373:Substance P; D016291:Dizocilpine Maleate; D018021:Lithium Chloride