REST increase helps to maintain cognitive function in a mild cognitive impairment of Alzheimer?s disease model

MARTIN S. GODOY; MARIA BEATRIZ BISTUÉ MILLÓN; MARIA EUGENIA NAVAS GUIMARAES; MARTIN A. BRUNO

Buenos Aires

Conferencia; Conference of Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN); 2016

FALAN

REST (repressor element 1-silencing trasnscriptor factor) is a repressor ofneuronal genes found in human and murine?s brains, which confers oxidativestress resistance and protects against toxic insults associated with Alzheimerdisease (AD). During adulthood, its level is basal and begins to increase in aging;however these levels are not increased in AD patient?s brains. On the other hand,during early stages of AD (Mild Cognitive Impairment, MCI) protector mechanismsfor oxidative stress are increased. We measure REST levels at different ages (3, 6and 12 months old) in prefrontal cortex of wild type rats and in a model of mildcognitive impairment of AD, the hemizygous McGill-R-Thy1-APP. This modeloverexpress human beta-amyloid peptide; and we found a significantly increase inREST levels starting as soon as six months old in the transgenic brain samplescompared to control rats. In addition, we measured CoREST and the histonemodifier involved in transcriptional repression LSD1, both forming a stable corecomplex with REST. Surprisingly, no significant changes were observed inCoREST and LSD1 cortical protein levels. We preformed learning and memory test(Morris water maze (MWM), and probe tests) and no significant differences werefound in the MWM test between transgenic and no transgenic rats, neither probetests nor quadrant analysis. These data as a whole suggest a protective effect of selectively increased REST on cognitive processes in our MCI rat model of AD