DAILY PATTERNS OF CLOCK NEGATIVE FACTORS ARE MODIFIED IN THE HIPPOCAMPU OF ABETA -INJECTED RAT

CORTEZ M; CASTRO A; CANGIANO B; SANCHEZ M; ALBA M; ANZULOVICH AC; GOMEZ MEJIBA SE; NAVIGATORE FONZO LS

MENDOZA

Congreso; SBCuyo 2022; 2022

Circadian disruption is prevalent in Alzheimer s disease (AD) and may contribute to cognitive impairment. At themolecular level, cellular oscillators consist of a network of interlocking transcriptional translational feedback loops. Thepositive limb of the loop is represented by the transcription factors CLOCK and BMAL1, which heterodimerize and bindto E-box sites in the promoters of the clock negative factors, period (PER1-3), and cryptochrome (CRY1-2) genes. Anegative feedback loop is achieved when the PERs and CRYs form heterocomplexes that translocate back to the nucleusand inhibit their own and other clock-controlled geneof the retinoic acid-related orphan receptor (ROR) family, complete the molecular clock machinery. Previously, we foundthat an intracerebroventricular (i.c.v. -42) modified the daily rhythms of BMAL1 and ROR expressionand cognition-related factors in the rat hippocampus. Taking into account those observations, the objective of this workwas to investigate the effects of an i.c.v. injection of amyloid beta peptide (1-42) on daily rhythms of PER1, PER2,CRY1,-injected groups were sacrificed throughout a 24-h period, and hippocampus samples were isolatedevery 6 h. Daily rhythms of clock genes expression were analyzed by RT-PCR, analyzed byimmunoblotting. Regulatory regions of clock PER1, PER2, CRY1, and CRY2 genes were scanned for E-box and ROREsites. We found that clock genes expression and A levels displayed daily oscillations in the rat hippocampus. We foundE- -42) modified daily rhythms ofclock genes expression and A uld modify the temporal patterns ofclock negative factors and consequently could affect the transcription of genes related to cognition in AD.