title: Role of stress system disturbance and enhanced novelty response in spatial learning of NCAM-deficient mice.
abstract: The neural cell adhesion molecule (NCAM) plays a crucial role in stress-related brain function, emotional behavior and memory formation. In this study, we investigated the functions of the glucocorticoid and serotonergic systems in mice constitutively deficient for NCAM (NCAM-/- mice). Our data provide evidence for a hyperfunction of the hypothalamic-pituitary-adrenal axis, with enlarged adrenal glands and increased stress-induced corticosterone release, but reduced hippocampal glucocorticoid receptor expression in NCAM-/- mice when compared to NCAM+/+ mice. We also obtained evidence for a hypofunction of 5-HT1A autoreceptors as indicated by increased 8-0H-DPAT-induced hypothermia. These findings suggest a disturbance of both humoral and neural stress systems in NCAM-/- mice. Accordingly, we not only confirmed previously observed hyperarousal of NCAM-/- mice in various anxiety tests, but also observed an increased response to novelty exposure in these animals. Spatial learning deficits of the NCAM-/- mice in a Morris Water maze persisted, even when mice were pretrained to prevent effects of novelty or stress. We suggest that NCAM-mediated processes are involved in both novelty/stress-related emotional behavior and in cognitive function during spatial learning.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg , Hamburg , Germany .
authors.forename: Joerg
authors.initials: J
authors.lastname: Brandewiede
authors.forename: Mira
authors.initials: M
authors.lastname: Jakovcevski
authors.forename: Oliver
authors.initials: O
authors.lastname: Stork
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D003345:Corticosterone / Q000097:blood; D006624:Hippocampus / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced; D018782:Maze Learning / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000172:deficiency*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: D019006:Neural Cell Adhesion Molecules; D011965:Receptors, Glucocorticoid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone