title: Associative and spatial learning and memory deficits in transgenic mice overexpressing the RNA-binding protein HuD.
abstract: HuD is a neuronal specific RNA-binding protein associated with the stabilization of short-lived mRNAs during brain development, nerve regeneration and synaptic plasticity. To investigate the functional significance of this protein in the mature brain, we generated transgenic mice overexpressing HuD in forebrain neurons under the control of the alphaCaMKinII promoter. We have previously shown that one of the targets of HuD, GAP-43 mRNA, was stabilized in neurons in the hippocampus, amygdala and cortex of transgenic mice. Animals from two independent lines expressing different levels of the transgene were subjected to a battery of behavioral tests including contextual fear conditioning and the Morris water maze. Our results show that although HuD is increased after learning and memory, constitutive HuD overexpression impaired the acquisition and retention of both cued and contextual fear and the ability to remember the position of a hidden platform in the Morris water maze. No motor-sensory abnormalities were observed in HuD transgenic mice, suggesting that the poor performance of the mice in these tests reflect a true cognitive impairment. We conclude that posttranscriptional regulation of gene expression by stabilization of specific mRNAs may have to be restricted temporally and spatially for proper acquisition and storage of memories.
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico HSC, Albuquerque, NM 87131, USA. fbolognani@salud.unm.edu
authors.forename: Federico
authors.initials: F
authors.lastname: Bolognani
authors.forename: Shenfeng
authors.initials: S
authors.lastname: Qiu
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Tanner
authors.forename: Jiae
authors.initials: J
authors.lastname: Paik
authors.forename: Nora I
authors.initials: NI
authors.lastname: Perrone-Bizzozero
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Weeber
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D051959:ELAV Proteins / Q000378:metabolism*; D000067779:ELAV-Like Protein 4; D005239:Fear; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016548:Prosencephalon / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013037:Spatial Behavior / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498011:Elavl4 protein, mouse; D012333:RNA, Messenger