title: Up-regulation of genes involved in cellular stress and apoptosis in a rat model of hippocampal degeneration.
abstract: Changes in gene expression within the hippocampus induced by denervation after electrolytic fimbria-fornix lesion in rat were compared to morphological and biochemical alterations. Fimbria-fornix lesion results in degeneration of hippocampal cholinergic terminals as evidenced by a sustained (2 days to 1 month) decrease in cholineacetyltransferase (ChAT) activity (50%). These changes were accompanied by a decrease in growth associated protein 43 (GAP-43) immunoreactivity in all hippocampal layers 4 days after lesion followed by a subsequent increase and return to normal levels by 20 days postinjury. This increase in GAP-43 expression in the hippocampus between 7 to 20 days after lesion may reflect heterotypic sprouting. TUNEL-positive cells were revealed by in situ assay within the hippocampus at 10 days, but not at 3 days, after lesion. Two subtracted cDNA libraries from the dorsal hippocampus of control and injured rats (at 3 and 10 days postlesion) were constructed in order to search for new genes potentially implicated in degeneration/regeneration phenomena. We analysed 1,536 clones from each library by differential screening and found a total of 46 up-regulated genes. Among the 15 known genes, 6 coded for proteins involved in signal transduction pathways. The upregulation of growth arrest DNA damage induced gene (GADD153), brain-specific RING finger protein, JNK interacting protein (JIP-1), protein kinase A (PKA), and Na+K+ ATPase was studied by quantitative polymerase chain reaction (PCR). Two of these genes, GADD153 and JIP-1, have been previously shown to participate in cell modifications induced by stress and apoptosis.
authors.affiliation: Synthélabo Recherche, CNS Research Department, Bagneux, France. eanguelo@bagneux.synthelabo.fr
authors.forename: E
authors.initials: E
authors.lastname: Anguelova
authors.forename: S
authors.initials: S
authors.lastname: Boularand
authors.forename: J P
authors.initials: JP
authors.lastname: Nowicki
authors.forename: J
authors.initials: J
authors.lastname: Benavides
authors.forename: T
authors.initials: T
authors.lastname: Smirnova
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001667:Binding, Competitive / Q000235:genetics; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D053938:DNA Fragmentation; D017931:DNA Primers; D003714:Denervation; D004195:Disease Models, Animal; D020712:Fornix, Brain / Q000201:enzymology / Q000473:pathology; D019922:GAP-43 Protein / Q000032:analysis / Q000276:immunology; D015870:Gene Expression / Q000502:physiology; D015723:Gene Library; D005820:Genetic Testing; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology*; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008297:Male; D009410:Nerve Degeneration / Q000201:enzymology / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017931:DNA Primers; D019922:GAP-43 Protein; D002795:Choline O-Acetyltransferase