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Patterns of status epilepticus-induced substance P expression during development
1Epilepsy Research Laboratory, Veteran Administration Medical Center, Sepulveda, CA 91343, USA. htliu@ucla.edu
Insights
Seizure activity in developing rats triggers age-specific hippocampal substance P expression. This neuropeptide
Area of Science:
- Neuroscience
- Developmental Biology
- Epilepsy Research
Background:
- Substance P (SP) is a neuropeptide involved in synaptic excitability.
- SP can be induced by various stimuli, but its developmental expression in epilepsy is not well understood.
Purpose of the Study:
- To investigate the age-dependent and region-specific expression of hippocampal substance P following status epilepticus in developing rats.
- To explore the relationship between seizure activity and substance P induction.
Main Methods:
- Lithium-pilocarpine-induced status epilepticus model in rats of different ages (2-week-old to adult).
- Immunohistochemistry to detect substance P expression.
- In situ hybridization to analyze preprotachykinin-A mRNA levels.
- NMDA receptor antagonist (MK-801) administration to block seizures.
Main Results:
- Status epilepticus induced age-specific patterns of substance P expression in the hippocampus.
- Maximal SP induction in CA1 was observed in 2-week-old rats, decreasing with age.
- CA3 and dentate gyrus showed increased SP neuron numbers and axon terminals in older rats.
- Preprotachykinin-A mRNA significantly increased in hippocampus post-seizure.
- MK-801 blocked both seizures and SP induction in young rats.
Conclusions:
- Seizure activity selectively induces age-dependent and region-specific expression of substance P in the developing hippocampus.
- This suggests a critical role for SP in the immature brain's response to seizures.
Abstract:
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.