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IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function.
Pardo, Joaquín; Abba, Martin C; Lacunza, Ezequiel; Ogundele, Olalekan M; Paiva, Isabel; Morel, Gustavo R; Outeiro, Tiago F; Goya, Rodolfo G.
Afiliação
  • Pardo J; INIBIOLP-Histology B-Pathology B, University of La Plata, La Plata, Argentina.
  • Abba MC; CINIBA, School of Medicine, University of La Plata, La Plata, Argentina.
  • Lacunza E; CINIBA, School of Medicine, University of La Plata, La Plata, Argentina.
  • Ogundele OM; Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge.
  • Paiva I; Department of Experimental Neurodegeneration, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Germany.
  • Morel GR; INIBIOLP-Histology B-Pathology B, University of La Plata, La Plata, Argentina.
  • Outeiro TF; Department of Experimental Neurodegeneration, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Germany.
  • Goya RG; Max Planck Institute for Experimental Medicine, Göttingen, Germany.
J Gerontol A Biol Sci Med Sci ; 73(4): 459-467, 2018 03 14.
Article em En | MEDLINE | ID: mdl-28645186
In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome. In the Barnes maze test, experimental rats showed a significantly higher exploratory frequency of the goal hole than controls. Hippocampal RNA-sequencing showed that 219 genes are differentially expressed in 28-month-old rats intracerebroventricularly injected with an adenovector expressing rat IGF-I as compared with placebo adenovector-injected counterparts. From the differentially expressed genes, 81 were down and 138 upregulated. From those genes, a list of functionally relevant genes, concerning hippocampal IGF-I expression, synaptic plasticity as well as neuronal function was identified. Our results provide an initial glimpse at the molecular mechanisms underlying the neuroprotective actions of IGF-I in the aging brain.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Fator de Crescimento Insulin-Like I / Terapia Genética / Memória Espacial / Hipocampo / Transtornos da Memória Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Gerontol A Biol Sci Med Sci Assunto da revista: GERIATRIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Fator de Crescimento Insulin-Like I / Terapia Genética / Memória Espacial / Hipocampo / Transtornos da Memória Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Gerontol A Biol Sci Med Sci Assunto da revista: GERIATRIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos