DIVERGENT EXPRESSION PATTERNS OF GENES INVOLVED IN LIPID METABOLISM DURING EARLY DEVELOPMENT MAY UNDERLIE DIFFERENCES IN ADULT BRAIN MORPHOLOGY IN SEIZURE-PRONE AND SEIZURE-RESISTANT RATS
Abstract number :
1.177
Submission category :
Year :
2003
Submission ID :
1899
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Krista L. Gilby, Peter Crino, Dan C. McIntyre Psychology, Neuroscience Institute, Carleton University, Ottawa, ON, Canada; Neurology, University of Pennsylvania Medical Center, Philadelphia, PA; Psychology, Neuroscience Institute, Carleton University, Ott
Rat strains that were selectively bred to be seizure-prone or seizure-resistant have been shown to exhibit differences in adult brain morphology. In seizure-prone animals the ventricles and piriform cortex are significantly larger than in seizure-resistant animals, while the corpus callosum and dorsal hippocampus are significantly smaller. The mechanism through which these differences in brain morphology arise remains unknown.
We used a number of gene screening technologies to investigate putative differences in gene expression that arise during ontogenesis of the strains which may, in turn, implicate underlying genetic control mechanisms that operate differently during critical periods of development. These techniques included superarrays and differential display.
Of nearly 2500 genes sampled, the results of this study revealed only 3 differences in gene expression between the strains during embryogenesis. When cDNA from the head of embryonic day 21 (E21) rats from each strain was probed using superarray technology, mRNA levels for apolipoprotein E (ApoE) and the beta 2 subunit of the sodium channel were shown to be significantly reduced in seizure-prone rats. In addition, when differential display was used to examine differences in gene expression between the strains at varying embryonic time points (E11, E13, E15, E19 and E21) alpha 2 macroglobulin was shown to be expressed at E11 in seizure-prone rats but was not expressed until E13 in seizure-resistant rats.
Clearly, divergent expression patterns occur for a very limited number of developmentally important genes during early embryogenesis of the strains. Interestingly, both ApoE and alpha-2 macroglobulin are intricately involved in lipid metabolism and reelin-based control of brain formation. These findings suggest that alterations in the timing and/or degree of expression for ApoE or alpha 2 macroglobulin, such as those shown here in the two strains, may be critical to initiate developmental cascades that give rise to the different brain morphologies, and possibly the differing seizure vulnerabilities characterized by the seizure-prone and the seizure-resistant phenotypes.
[Supported by: CIHR]