title: Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory.
abstract: Neuronal ELAV-like proteins (HuB, HuC, and HuD) are highly conserved RNA-binding proteins able to selectively associate with the 3' UTR of a subset of target mRNAs and increase their cytoplasmic stability and rate of translation. We previously demonstrated the involvement of these proteins in learning, reporting that they undergo a sustained up-regulation in the hippocampus of mice trained in a spatial discrimination task. Here, we extend this finding, showing that a similar up-regulation occurs in the hippocampus of rats trained in another spatial learning paradigm, the Morris water maze. HuD, a strictly neuron-specific ELAV-like protein, is shown to increase after learning, with a preferential binding to the cytoskeletal fraction. HuD up-regulation is associated with an enhancement of GAP-43 mRNA and protein levels, with an apparently increased HuD colocalization with the GAP-43 mRNA and an increased association of neuronal ELAV-like proteins with the GAP-43 mRNA. These learning-dependent biochemical events appear to be spatiotemporally controlled, because they do not occur in another brain region involved in learning, the retrosplenial cortex, and at the level of protein expression they show extinction 1 month after training despite memory retention. By contrast, HuD mRNA levels still remain increased after 1 month in the CA1 region. This persistence may have implications for long-term memory recall.
authors.affiliation: Department of Experimental and Applied Pharmacology, University of Pavia, Via Taramelli 14, 27100 Pavia, Italy. alessia.pascale@unipv.it
authors.forename: Alessia
authors.initials: A
authors.lastname: Pascale
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Gusev
authors.forename: Marialaura
authors.initials: M
authors.lastname: Amadio
authors.forename: Tania
authors.initials: T
authors.lastname: Dottorini
authors.forename: Stefano
authors.initials: S
authors.lastname: Govoni
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Alkon
authors.forename: Alessandro
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D000818:Animals; D051959:ELAV Proteins; D019922:GAP-43 Protein / Q000032:analysis / Q000235:genetics*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D016601:RNA-Binding Proteins / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D051959:ELAV Proteins; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins