Remor 2018 Mol Neurobiol
|Remor AP, da Silva RA, de Matos FJ, Glaser V, de Paula Martins R, Ghisoni K, da Luz Scheffer D, Andia DC, Portinho D, de Souza AP, de Oliveira PA, Prediger RD, Torres AI, Linhares RMM, Walz R, Ronsoni MF, Hohl A, Rafacho A, Aguiar AS Jr, De Paul AL, Latini A (2018) Chronic metabolic derangement-induced cognitive deficits and neurotoxicity are associated with REST inactivation. Mol Neurobiol 56:1539-57.|
Remor AP, da Silva RA, de Matos FJ, Glaser V, de Paula Martins R, Ghisoni K, da Luz Scheffer D, Andia DC, Portinho D, de Souza AP, de Oliveira PA, Prediger RD, Torres AI, Linhares RMM, Walz R, Ronsoni MF, Hohl A, Rafacho A, Aguiar AS Jr, De Paul AL, Latini A (2018) Mol Neurobiol
Abstract: 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.
Labels: MiParea: Respiration, nDNA;cell genetics, Pharmacology;toxicology Pathology: Obesity
Organism: Rat Tissue;cell: Nervous system Preparation: Intact cells
Coupling state: LEAK, OXPHOS Pathway: N HRR: Oxygraph-2k