View Project Koh-2K08NS002068-04

Project Summary
Status:	Public
Publications:	1 Published
Project Detail		Data Detail
Platform:	Affymetrix	MIAME Areas	Compliance
Species:	Rat	Array Design Detail	true
Organ/Tissue Type:	brain	Experiment Detail	false
Organ Region:	hippocampus	Sample Detail	false
Cell Type:	mixed neural cells	Hybridization Detail	true
Study Type:	time_series_design	Measurement Detail	true
Disease/Condition:	Epilepsy
Replicates:	3
Expected Samples:

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Investigator Contact Detail
Name	Sookyong Koh
Street Address:	BOX 51 Division of Neurology, Children's Memorial Hospital
	Northwestern Med School, 2300 Children's Plaza
City, State/Province:	Chicago , IL
Zip/Postal Code:	60614
Country:	United States
Work Phone:	773-880-3179
Fax:	773-880-3374
E-mail:	skoh@childrensmemorial.org

Proposal Detail

Grant:

2K08NS002068-04

Status:

Public

Service Type:

Start to Finish Profiling

IACUC:

A3303-01

IACUC date:

2001-05-07

Study Relevance:

Early childhood convulsions have been correlated with hippocampal neuron loss in patients with intractable temporal lobe epilepsy. Using a "two-hit" rat seizure model, we have shown that animals subjected to kainate (KA)- or hypoxia-induced seizures during early postnatal period showed no cell death, yet sustained more extensive neuronal death after second seizures in adulthood. An early life seizure, without causing overt cellular injury, predisposes the brain to the damaging effect of seizures in later life. Cellular and molecular changes that accompany early seizures and that lead to subsequent epileptogenesis and increased susceptibility to seizure-induced neuronal injury, however, remain poorly understood. We propose to investigate age-specific, time-dependent changes in gene expression that may underlie this priming effect of early-life seizures.

Hypothesis:

Previous studies have shown that AMPA receptor subtype of glutamate receptors play a crucial role in the age-specific vulnerability and in the long-term epileptogenic effects of perinatal hypoxia seizures. We found that AMPA receptor antagonists block the increased susceptibility caused by early life seizures to later seizures and seizure-induced brain damage. We hypothesize that an alteration of AMPA receptor composition is one of many changes caused by early-life seizures that leads to an increase in Ca2+ permeability, which then results in cascade of downstream events and modifies array of gene expression that promote epileptogenesis and susceptibility to neuronal death in later life.

Specific Aim:

We will determine the sequence of gene expression pattern in the hippocampus at various times following KA induced seizures at postnatal day (P) 15.

Experimental Procedure and Design:

We will examine three time points: 1hr, 72 hr, and 15 days following systemic KA-induced seizures at P15 as we have previously observed structural changes within the hippocampus at these time points. Within an hour of KA seizures, a marked swelling of dendrites, disassembly of dendritic microtubules and glycogen depletion are observed by electron microscopy. Within 5 days, basal dendrites of CA3 hippocampal pyramidal neurons show abnormal spine morphology and decreased branching pattern. 15 days after the seizures, aberrant growth of mossy fibers in the CA3 stratum oriens is observed in animals exposed to KA. Ten hippocampi will be pooled from five animals treated with KA (3mg/kg i.p.) and from five littermate controls injected with PBS. Animals will be decapitated and hippocampi will be rapidly dissected from the brain, flash frozen in liquid nitrogen, and stored at -80C until extraction of total RNA, which will be sent to the center. We will provide 4 tissue samples-2 controls and 2 KA, each a pool of five animals - for each time points. Mixing tissues from multiple rats will normalize single nucleotide polymorphisms and tissue heterogeneity.

Experimental Factors:

Conditions that are tested in the experiment. At least one is required. Experimental factors are the independent variables in the experiment.


Experimental Factors is empty.

Project Samples

Samples associated with this project.

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Name	Description	Extracts
Ctr-240h-P15-I	Control rats 240h after inj...	1
Ctr-240h-P15-II	Control rats 240h after inj...	1
Ctr-240h-P15-III	Control rats 240h after inj...	1
KA-1h-P15-I	Rats 1h after injection wit...	1
KA-1h-P15-II	Rats 1h after injection wit...	1
KA-1h-P15-III	Rats 1h after injection wit...	1
KA-6h-P15-I	Rats 6h after injection wit...	1
KA-6h-P15-II	Rats 6h after injection wit...	1
KA-6h-P15-III	Rats 6h after injection wit...	1
KA-24h-P15-I	Rats 24h after injection wi...	1
KA-24h-P15-II	Rats 24h after injection wi...	1
KA-24h-P15-III	Rats 24h after injection wi...	1
KA-72h-P15-I	Rats 72h after injection wi...	1
KA-72h-P15-II	Rats 72h after injection wi...	1
KA-72h-P15-III	Rats 72h after injection wi...	1
KA-240h-P15-I	Rats 240h after injection w...	1
KA-240h-P15-II	Rats 240h after injection w...	1
KA-240h-P15-III	Rats 240h after injection w...	1
Ctr-1h-P15-I	Control rats 1h after injec...	1
Ctr-1h-P15-II	Control rats 1h after injec...	1
Ctr-1h-P15-III	Control rats 1h after injec...	1
Ctr-6h-P15-I	Control rats 6h after injec...	1
Ctr-6h-P15-II	Control rats 6h after injec...	1
Ctr-6h-P15-III	Control rats 6h after injec...	1
Ctr-24h-P15-I	Control rats 24h after inje...	1
Ctr-24h-P15-II	Control rats 24h after inje...	1
Ctr-24h-P15-III	Control rats 24h after inje...	1
Ctr-72h-P15-I	Control rats 72h after inje...	1
Ctr-72h-P15-II	Control rats 72h after inje...	1
Ctr-72h-P15-III	Control rats 72h after inje...	1

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