COMBINATION TREATMENT WITH PPARγAGONIST PIOGLITAZONE AND RETINOIC ACID MODIFIES DAILY PATTERNS OF APO E IN THE TEMPORAL CORTEX OF AN EXPERIMENTAL MODEL OF ALZHEIMER DISEASE

CORIA LUCERO; LEDESMA CARINA; CASTRO, ANDREA; DELGADO S.M; ANZULOVICH, AC; NAVIGATORE FONZO, L

Congreso; XXXIII CONGRESO ANUAL SAN 2018; 2018

Numerousstudies has shown that animbalance between the production and clearance ofamyloid-β (Aβ) peptides in the brainresults in accumulation of Aβ. The removalof Aβ deposits is a process facilitated by apolipoprotein E (ApoE).ApoEexpression is transcriptionally induced by PPARγ in coordination with RXRs. Onthe other hand, absence of ApoE has been correlated with diminished antioxidantcapacity. Previously,we found that an i.c.v. injection of Aβ(1-42) modified thedaily rhythms of lipid peroxidation and protein carbonyls in the rat cortex.Taking into account those observations, the objectives of this study were:first, to analyze the effect of an i.c.v. injection of Aβ(1-42) on the 24hrhythms of Aβ, BMAL1 and ApoE protein levels in the rat temporal cortex;second, to evaluate the effect of pioglitazone-retinoic acid (Pio-RA) on thosetemporal patterns.Four-month-old male Holtzman rats were divided into threegroups defined as:1)control 2)Aβ-injected 3)Aβ-injected treated with Pio-RA. Aβ,BMAL1 and ApoE proteins levels were analyzed by immunoblotting. Lipidperoxidation and protein carbonyls levels by colorimetric assays and ELISA,respectively.We found that injection of Aβ(1-42) phase shifted Aβ, BMAL1 and ApoErhythms. Noteworthy, Pio-RA reestablished rhythmicity of those temporalpatterns indicating PPARg-RXR heterodimer might be a transcription factorinvolved in circadian regulation and a potential target for restoration ofdaily rhythmicity of Apo E in AD.