DAILY RHYTHM OF TNFalpha IS MODIFIED IN THE PREFRONTAL CORTEX OF AN EXPERIMENTAL MODEL OF ALZHEIMER´S DISEASE

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

San Luis

Congreso; SOCIEDAD DE BIOLOGÍA DE CUYO- XXXV REUNIÓN CIENTÍFICA ANUAL; 2017

SOCIEDAD DE BIOLOGÍA DE CUYO

DAILY RHYTHM OF TNFalpha IS MODIFIED IN THE PREFRONTAL CORTEX OF AN EXPERIMENTAL MODEL OF ALZEHIMER?S DISEASELedezmaC,Anzulovich AC,Delgado SM and NavigatoreFonzo L. Lab. de Cronobiología, IMIBIO-CONICET-UNSL, SL. E-mail: lorenavigfz@yahoo.com.ar.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 ofneurodegenerative 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 ofagregated β-amyloid (1-42),on temporal patterns of TNFα, BMAL1, RORa, and Aβ protein levels, in the prefrontalcortex offour-month-old males Holtzman rats. Groups were defined as: control (CO) and Aβ-injected (Aβ). Rats were maintained under 12h-light:12h-dark conditionsthroughout 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 ani.c.v. injection of Aβ (1-42) modified the dailyvariation of TNFα, BMAL1, RORa, and Aβ protein in the rat prefrontal cortex. These findings mightcontributeto the knowledgeon the relationship between TNF-mediated neuroinflammation and altered circadian rhythms in the AD.KEYWORDS: RORa, TNFα, circadian rhythms, Alzheimer disease, prefrontal cortex