EFFECT OF AN I.C.V. INJECTION OF AGREGATED BETA-AMYLOID (1-42) ON THE CIRCADIAN EXPRESSION OF REV-ERBβ and RORα IN THE RAT HIPPOCAMPUS

MAZZAFERRO P; CASTRO A; GOLINI RS; GARRAZA, M; ANZULOVICH AC; DELGADO SM; NAVIGATORE FONZO LS

Merlo, San Luis

Congreso; XXXV Reunión Anual de la Sociedad de Biología de Cuyo; 2017

Alzheimer disease (AD) is the most frequent form of dementia in the elderly. It is characterized by a progressive cognitive decline and circadian rhythms alterations. At the cellular level, circadian rhythms are generated by two interacting transcription/translation feedback loops, a positive loop constituted by the transcriptional activator BMAL1:CLOCK and a negative loop established by phosphorylated PER-CRY repressor complexes. The REV-ERB/ROR orphan nuclear receptor family regulates the expression of Bmal1 gene and contributes to the robustness of the clock mechanism. The objective of this work was to investigate the effects of an i.c.v. injection of aggregated beta amyloid (1-42) on the circadian patterns of REV-ERBβ and RORα expression, as well as on oscillating BMAL1 and Aβ protein levels, throughout a 24 h period, in the rat hippocampus (CICUA:B-263/17). Four-month-old males Holtzman rats were divided into two groups defined as: control (CO) and Aβ-injected (Aβ) groups (Zhang 2013). Rats were maintained under 12h-light:12h-dark lighting conditions and received water and food ad libitum. Hippocampus samples were isolated every 4 h during a 24h. REV-ERBβ and RORα mRNA levels were determined by RT-PCR. Aβ and BMAL1 proteins were assessed by immunoblotting. We found that an i.c.v. injection of aggregated Aβ(1-42) increased Aβ peptide content in the rat hippocampus and phase shifted daily rhythms of Aβ, BMAL1, Rev-Erbβ and Rorα expression. Therefore, elevated levels of Aβ peptides could modify the temporal patterns of clock genes in the hippocampus. These observations would contribute to a better understanding of clock involvement in the pathogenesis of the AD.