title: GAP-43 gene expression regulates information storage.
abstract: Previous reports have shown that overexpression of the growth- and plasticity-associated protein GAP-43 improves memory. However, the relation between the levels of this protein to memory enhancement remains unknown. Here, we studied this issue in transgenic mice (G-Phos) overexpressing native, chick GAP-43. These G-Phos mice could be divided at the behavioral level into "spatial bright" and "spatial dull" groups based on their performance on two hidden platform water maze tasks. G-Phos dull mice showed both acquisition and retention deficits on the fixed hidden platform task, but were able to learn a visible platform task. G-Phos bright mice showed memory enhancement relative to wild type on the more difficult movable hidden platform spatial memory task. In the hippocampus, the G-Phos dull group showed a 50% greater transgenic GAP-43 protein level and a twofold elevated transgenic GAP-43 mRNA level than that measured in the G-Phos bright group. Unexpectedly, the dull group also showed an 80% reduction in hippocampal Tau1 staining. The high levels of GAP-43 seen here leading to memory impairment find its histochemical and behavioral parallel in the observation of Rekart et al. (Neuroscience 126: 579-584) who described elevated levels of GAP-43 protein in the hippocampus of Alzheimer's patients. The present data suggest that moderate overexpression of a phosphorylatable plasticity-related protein can enhance memory, while excessive overexpression may produce a "neuroplasticity burden" leading to degenerative and hypertrophic events culminating in memory dysfunction.
authors.affiliation: Department of Psychology and Neurobiology, Northwestern University Interdepartmental Neuroscience Program, Northwestern University, Evanston, Illinois 60208, USA. matthew_holahan@carleton.ca
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Holahan
authors.forename: Kyle S
authors.initials: KS
authors.lastname: Honegger
authors.forename: Nino
authors.initials: N
authors.lastname: Tabatadze
authors.forename: Aryeh
authors.initials: A
authors.lastname: Routtenberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins; D002645:Chickens; D019922:GAP-43 Protein / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010375:Pedigree; D012333:RNA, Messenger / Q000378:metabolism; D012153:Retention, Psychology; D013028:Space Perception; D013194:Staining and Labeling; D013550:Swimming; D014796:Visual Perception
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D019922:GAP-43 Protein; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; C491177:Slc30a3 protein, mouse; C085348:tau-1 monoclonal antibody