DAILY RHYTHM OF TNFalpha IS MODIFIED IN THE PREFRONTAL CORTEX OF AN EXPERIMENTAL MODEL OF ALZEHIMER?S DISEASE

LEDEZMA, C; ANZULOVICH AC; DELGADO SM; NAVIGATORE FONZO LS

MERLO, SAN LUIS

Congreso; XXXV REUNION CIENTIFICA ANUAL DE LA SOCIEDAD DE BIOLOGIA DE CUYO; 2017

Alzheimer?s disease (AD) is the most common form of elderly dementia. Recent research has shown that inflammatory mechanisms have a key role in the pathogenesis of AD. TNF-α is a proinflammatory cytokine implicated in the pathogenesis of neurodegenerative diseases, such as AD. Besides cognitive deficit, AD patients show alterations in their circadian rhythms. The objective of this work was to investigate the effects of an i.c.v. injection of agregated β-amyloid (1-42), on temporal patterns of TNFα, BMAL1, RORa, and Aβ protein levels, in the prefrontal cortex of four-month-old males Holtzman rats. Groups were defined as: control (CO) and Aβ-injected (Aβ). Rats were maintained under 12h-light:12h-dark conditions throughout the entire experimental period. Prefrontal cortex samples were isolated every 4 h during a 24h period. Protein levels were analyzed by Western blots. We found an i.c.v. injection of Aβ (1-42) modified the daily variation of TNFα, BMAL1, RORa, and Aβ protein in the rat prefrontal cortex. These findings might contribute to the knowledge on the relationship between TNF-mediated neuroinflammation and altered circadian rhythms in the AD.