Gene x environment interaction and cognitive performance: animal studies on the role of corticosterone.
A fundamental question in the neurobiology of cognition is how stress and glucocorticoids modify learning and memory processes. Why some individuals develop cognitive deficits after stress, while other individuals improve in cognitive performance under similar adverse conditions is still unresolved. To address these questions we focus on those issues. First, corticosterone, which appears to be the preferred glucocorticoid for the rodent and human brain, acts via brain mineralocorticoid (MR) and glucocorticoid receptors (GR) on the expression of networks of corticosteroid-responsive genes. Different effects are achieved by MR and GR activation. Second, the experimental context that determines the timing and the consequences of corticosterone action during the various stages of information processing is reviewed. Third, the genetic context and the environmental context are investigated. Using apolipoprotein E knockout (apoE0/0) mice we show that apoE (apoE4 is a genetic risk factor for Alzheimer's disease) is a candidate gene with an important function in shaping the cognitive outcome (genotype x environment interaction).
de Kloet
E Ronald
ER
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, PO Box 9502, 2300 RA Leiden, The Netherlands. e.kloet@lacdr.leidenuniv.nl
Grootendorst
Jeannette
J
Karssen
Adriaan M
AM
Oitzl
Melly S
MS
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003345:Corticosterone / Q000494:pharmacology*; D004777:Environment; D005838:Genotype; D051379:Mice; D008817:Mice, Mutant Strains; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009446:Neurobiology; D011965:Receptors, Glucocorticoid / Q000187:drug effects*
D001057:Apolipoproteins E; D019006:Neural Cell Adhesion Molecules; D011965:Receptors, Glucocorticoid; D003345:Corticosterone