Chronobiology
Author: Mayra Cortez | Email: lorenavigfz@yahoo.com.ar
Mayra Cortez 1°, Melisa Sanchez 1°, Rebeca Golini 1°, Richard Alba 1°, Sandra Gomez Mejiba 1°, Dario Ramirez 1°, Silvia Delgado 1°, Ana Cecilia Anzulovich 1°, Lorena Navigatore Fonzo 1°
1° Laboratorio. de Cronobiología, IMIBIO-CONICET-UNSL
Alzheimer’s disease(AD) is a neurodegenerative disorder causes dementia in the elderly. The accumulation of Aβ in the brain plays a key role in the pathogenesis of AD. In the amyloidogenic pathway, Aβ generation is mediated by amyloid precursor protein processing that is subsequently proteolysis by β/γ-secretases. Elevated levels of Aβ causes an increase in oxidative damage Besides cognitive deficits, AD patients show alterations in their circadian rhythms. Previously, we found that an intracerebroventricular (i.c.v) injection of Aβ(1-42) modified the daily patterns of Tbars and protein carbonyl in the rat hippocampus. Taking into account those observations, our objective was to investigate the effects of an i.c.v injection of Aβ(1-42) on daily rhythms of β/γ-secretases, BMAL protein levels, and chlorotyrosine and nitrotyrosine levels in the rat hippocampus. Four-month-old males Holtzman rats were divided into two groups defined as: control and Aβ-injected. Daily rhythms of β/γ-secretases expression were analyzed by RT-PCR, chlorotyrosine and nitrotyrosine levels were determined by ELISA and BMAL levels by Western blots. We found that an i.c.v. injection of Aβ(1-42) modified variation of β/γ–secretases, BMAL1,chlorotyrosine and nitrotyrosine. Thus, elevated Aβ peptide levels alter temporal patterns of nitrosative stress-related parameters and, consequently, would negatively affect cellular clock activity and the transcription of their target genes.