Stress alleviates reduced expression of cell adhesion molecules (NCAM, L1), and deficits in learning and corticosterone regulation of apolipoprotein E knockout mice
Cell adhesion molecules (CAMs) involved in synaptic changes underlying learning and memory processes, are implicated in the effect of stress on behavioural performance. The present study was designed to test the hypothesis that (i) expression of CAMs is apolipoprotein E- (apoE) genotype dependent and (ii) repeated exposure to stress modulates the synthesis of CAMs in an apoE-genotype dependent manner. Using ELISA we tested this hypothesis and measured expression of NCAM and L1 in different brain regions of naive and stressed apolipoprotein E-knockout (apoE0/0) and C57Bl6 (wild-type) mice. Naive apoE0/0 mice had elevated basal morning corticosterone and ACTH concentrations and decreased expression of NCAM and L1 compared to wild-type mice. Repeated exposure of mice to rats, as the common stressor, alleviated the reduction in expression of CAMs in apoE0/0 mice; seven days after the last rat exposure, expression of NCAM was increased in frontal brain and hippocampus whereas expression of L1 was increased in hippocampus and cerebellum. Rat stress attenuated the elevation of basal morning corticosterone concentration in apoE0/0 mice towards concentrations detected in wild-type mice. Moreover, rat stress improved learning and memory of apoE0/0 mice in the water maze. In conclusion, repeated exposure to stress eliminated apoE-genotype-related differences in expression of CAMs. Under these same conditions the differences in cognitive performance and corticosterone concentrations were abolished between wild type and apoE0/0 mice.
Keywords: Adrenocorticotropic Hormone/blood ; Animals ; Apolipoproteins E/ deficiency/genetics ; Brain/growth & development/ metabolism ; Cell Adhesion Molecules ; Neuronal/ biosynthesis/genetics ; Corticosterone/ blood ; Down-Regulation/ genetics ; Genotype ; Learning Disorders/genetics/ metabolism/physiopathology ; Leukocyte L1 Antigen Complex ; Male ; Maze Learning/physiology ; Membrane Glycoproteins/biosynthesis/genetics ; Mice ; Mice ; Knockout ; Neural Cell Adhesion Molecules/biosynthesis/genetics ; Stress/genetics/ metabolism
Author address: Division of Medical Pharmacology, LACDR and Leiden University Medical Center, Leiden University, PO Box 9503, 2300 RA Leiden, The Netherlands.
Record created on 2007-01-18, modified on 2016-08-08