title: Neurotrophic signaling molecules associated with cholinergic damage in young and aged rats: environmental enrichment as potential therapeutic agent.
abstract: The aim of this study was to determine the neurobiological bases of behavioral deficits associated with cholinergic damage and the potential of long-term environmental enrichment as a therapeutic agent. Rats were submitted to intra-structures injection of 192 IgG-saporin and then behaviorally tested 1 month and 1 year post-lesion in a nonmatching-to-position task. The gene expression changes were assessed by cDNA macroarray technology using the GE array Q series designed to profile the expression of neurotrophic signaling molecules. Results showed that (1) cholinergic injury modulated the expression of genes such as brain-derived neurotrophin factor but also genes associated with inflammatory response, neuron apoptosis, regulation of angiogenesis, and synaptic plasticity, (2) aging is associated with regulation of glial proliferation and apoptosis, and (3) long-term enriched environment housing enhanced behavioral performance in lesioned and non-lesioned rats and upregulated gene expression. This therapeutic role of the enriched environment seemed to be associated with a suppression of expression of genes involved in apoptosis, glial cell differentiation, and cell cycle, but also with an enhanced expression of a subset of genes involved in signal transduction.
authors.affiliation: Université d'Aix-Marseille I - Laboratoire de Neurobiologie Intégrative et Adaptative - UMR/CNRS 6149 - Pôle 3C - 3 Place Victor Hugo, 13331 Marseille Cedex 03, France. veronique.paban@univ-provence.fr
authors.forename: Véronique
authors.initials: V
authors.lastname: Paban
authors.forename: Caroline
authors.initials: C
authors.lastname: Chambon
authors.forename: Christine
authors.initials: C
authors.lastname: Manrique
authors.forename: Claude
authors.initials: C
authors.lastname: Touzet
authors.forename: Béatrice
authors.initials: B
authors.lastname: Alescio-Lautier
mesh_terms: D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D018678:Cholinergic Agents / Q000378:metabolism / Q000633:toxicity; D004195:Disease Models, Animal; D004777:Environment; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054789:Ribosome Inactivating Proteins, Type 1 / Q000633:toxicity; D000076985:Saporins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D019208:Brain-Derived Neurotrophic Factor; D018678:Cholinergic Agents; D012333:RNA, Messenger; D054789:Ribosome Inactivating Proteins, Type 1; D002795:Choline O-Acetyltransferase; D000076985:Saporins