title: Age-related cognitive impairments in mice with a conditional ablation of the neural cell adhesion molecule.
abstract: Most of the mechanisms involved in neural plasticity support cognition, and aging has a considerable effect on some of these processes. The neural cell adhesion molecule (NCAM) of the immunoglobulin superfamily plays a pivotal role in structural and functional plasticity and is required to modulate cognitive and emotional behaviors. However, whether aging is associated with NCAM alterations that might contribute to age-related cognitive decline is not currently known. In this study, we determined whether conditional NCAM-deficient mice display increased vulnerability to age-related cognitive and emotional alterations. We assessed the NCAM expression levels in the hippocampus and medial prefrontal cortex (mPFC) and characterized the performance of adult and aged conditional NCAM-deficient mice and their age-matched wild-type littermates in a delayed matching-to-place test in the Morris water maze and a delayed reinforced alternation test in the T-maze. Although aging in wild-type mice is associated with an isoform-specific reduction of NCAM expression levels in the hippocampus and mPFC, these mice exhibited only mild impairments in working/episodic-like memory performance. However, aged conditional NCAM-deficient mice displayed pronounced impairments in both the delayed matching-to-place and the delayed reinforced alternation tests. Importantly, the deficits of aged NCAM-deficient mice in these working/episodic-like memory tasks could not be attributed to increased anxiety-like behaviors or to differences in locomotor activity. Taken together, these data indicate that reduced NCAM expression in the forebrain might be a critical factor for the occurrence of cognitive impairments during aging.
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Bisaz
authors.forename: Pere
authors.initials: P
authors.lastname: Boadas-Vaello
authors.forename: David
authors.initials: D
authors.lastname: Genoux
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
mesh_terms: D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D003072:Cognition Disorders / Q000235:genetics*; D003623:Dark Adaptation / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D012054:Reinforcement, Psychology; D013550:Swimming / Q000502:physiology / Q000523:psychology
chemical_list: D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2