info:eu-repo/semantics/article
Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
Fecha
2019-03Registro en:
Remor, Aline Pertile; Da Silva, Rodrigo Augusto; de Matos, Filipe José; Glaser, Viviane; Paula Martins, Roberta de; et al.; Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation; Humana Press; Molecular Neurobiology; 56; 3; 3-2019; 1539-1557
0893-7648
CONICET Digital
CONICET
Autor
Remor, Aline Pertile
Da Silva, Rodrigo Augusto
de Matos, Filipe José
Glaser, Viviane
Paula Martins, Roberta de
Ghisoni, Karina
Luz Scheffer, Débora da
Andia, Denise Carleto
Portinho, Daniele
de Souza, Ana Paula
Oliveira, Paulo Alexandre de
Prediger, Rui Daniel
Torres, Alicia Ines
Linhares, Rose Marie Mueller
Walz, Roger
Ronsoni, Marcelo Fernando
Hohl, Alexandre
Rafacho, Alex
Aguiar, Aderbal Silva
de Paul, Ana Lucia
Latini, Alexandra
Resumen
Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromised cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in rats. The mechanisms appear to be linked to reduced active DNA demethylation and diminished expression of the neuroprotective transcription factor REST. The impact of the relationship between adiposity and DNA hypermethylation on REST expression was also demonstrated in peripheral blood mononuclear cells in obese children with reduced levels of blood ascorbate. The reversible nature of epigenetic modifications and the cognitive impairment reported in obese children, adolescents, and adults suggest that the correction of the anthropometry and the peripheral metabolic alterations would protect brain homeostasis and reduce the risk of developing neurodegenerative diseases.