title: Aging alters long-term potentiation--related gene networks and impairs synaptic protein synthesis in the rat hippocampus.
abstract: During aging, memory retention and persistence of long-term potentiation (LTP) are impaired, suggesting an aging-related deterioration in mechanisms regulating information storage. Late-phase LTP requires synthesis of proteins at synapses as well as integrated regulation of gene networks. Because aging diminishes the persistence of LTP, primarily by affecting the transition between early and late phases, we assessed whether this was reflected in perturbation of gene networks. Using DNA microarray analysis, we compared LTP-associated gene expression in young (5 months), middle-aged (15 months), and old (22 months) male Sprague-Dawley rats. As expected, we found no significant difference in LTP measured 20 minutes postinduction; however, we found that overall more genes were regulated in the young group. Bioinformatics predicted not only dysregulation of activator protein-1 and nuclear factor kB transcription factor activity and epigenetic modifications but also dysregulation of protein synthesis. Notably, we confirmed an age-related impairment in metabotropic and ionotropic receptor-mediated synaptic protein synthesis. Together, these results demonstrate that LTP-specific gene expression is altered with aging and suggest that dysregulation of synaptic protein synthesis also contributes to the age-dependent reduction in LTP persistence.
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Ryan
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Diane
authors.initials: D
authors.lastname: Guévremont
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Carthika
authors.initials: C
authors.lastname: Luxmanan
authors.affiliation: Brain Health Research Centre, University of Otago, Dunedin, New Zealand; Department of Psychology, University of Otago, Dunedin, New Zealand.
authors.forename: Wickliffe C
authors.initials: WC
authors.lastname: Abraham
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand. Electronic address: joanna.williams@otago.ac.nz.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Williams
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D019295:Computational Biology; D044127:Epigenesis, Genetic / Q000235:genetics; D015870:Gene Expression; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis / Q000235:genetics*; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D018808:Transcription Factor AP-1
keywords: Ingenuity pathway analysis; Microarray; Transcription factors; synaptic protein synthesis