Microarray analysis of postictal transcriptional regulation of neuropeptides
- 147 Downloads
Unlike adults, kainic acid (KA)-induced status epilepticus (SE) in immature rats causes neither cell death nor recurrent spontaneous seizures. To elucidate the mechanisms of these distinct responses, transcriptional changes in neuropeptides were examined following KA-induced SE. We aimed to determine whether neuropeptides with anticonvulsant/neuroprotective properties were preferentially increased in immature rats while those with a proconvulsant/neurotoxic role were elevated to a greater extent in mature rats. We used high-density oligonucleotide gene arrays and directly compared transcriptional regulation of seven select neuropeptides at P15 and P30 over five time points. Total RNAs were isolated from hippocampi of 12 animals and pooled to hybridize to triplicate Affymetrix Genechips. Microarray results were validated by real-time quantitative RT-PCR (qRT-PCR). Independent individual RNA samples were purified for triplicate runs of qRT-PCR. Neuropeptides are significantly regulated by seizures in both immature and mature hippocampus. The magnitude of increase is significantly higher at P30 compared with that at P15, not only for neuropeptides with neurotoxic/proconvulsant properties but also for those with neuroprotective/anticonvulsant properties. Galanin is induced at 24 h only in P30 rats. CST shows high expression in immature hippocampus and is further increased after KA-induced SE only in P15. The expression trends seen in the microarray data are confirmed by qRT-PCR for all six neuropeptides analyzed. CST might play a neuroprotective role in immature rats, and its overexpression might prevent neuronal loss after seizure in adults. Also, suppression of tachykinin and corticotropin-releasing hormone might be effective in alleviating seizure-induced neuronal damage.
Index EntriesEpilepsy gene expression hippocampus kainic acid seizure
- Cortes R., Ceccatelli S., Schalling M., and Hokfelt T. (1990) Differential effects of intracerebroventricular colchicine administration on the expression of mRNAs for neuropeptides and neurotransmitter enzymes, with special emphasis on galanin: an in situ hybridization study. Synapse 6, 369–391.PubMedCrossRefGoogle Scholar
- Liu H., Mazarati A. M., Katsumori H., Sankar R., and Wasterlain C. G. (1999) Sustance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus. Proc. Natl. Acad. Sci. U. S. A. 96, 5286–5291.PubMedCrossRefGoogle Scholar
- Perez J., Vezzani A., Civenni G., Tutka P., Rizzi M., Schupbach E., and Hoyer D. (1995) Functional effects of D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Trp-NH2 and differential changes in somatostatin receptor messenger RNAs, binding sites and somatostatin release in kainic acid-treated rats. Neuroscience 65, 1087–1097.PubMedCrossRefGoogle Scholar
- Senut M. C., Menetrey D., and Lamour Y. (1989) Cholinergic and peptidergic projections from the medial septum and the nucleus of the diagonal band of Broca to dorsal hippocampus, cingulate cortex and olfactory bulb: a combined wheatgerm agglutinin-apohorseradish peroxidase-gold immunohistochemical study. Neuroscience 30, 385–403.PubMedCrossRefGoogle Scholar