Role of LSD1 in inflammation and Cognition in a Transgenic Rat Model of AD-like pathology. Alzheimer's Association

BISTUE MILLON, MARIA BEATRIZ; NAVAS GUIMARAES, ARIA EUGENIA; BRUNO, MARTIN ALEJANDRO

Buenos Aires

Simposio; Alzheimer Association Satellite Symposium,; 2018

Alzheimer Association USA

LSD1 is a demethylase which participate with HDAC1/2, in the CoREST complex, recruited by REST to repress the expression of neuronal genes. LSD1 plays a role in cognition, memory and inflammatory responses. Understanding the epigenetic processes underlying memory formation, synaptic plasticity and neuroinflammation may also improve diagnosis and treatment of neurodegenerative diseases. To determine the role of LSD1 in these processes, we investigate the hippocampal levels of LSD1 and its correlation with the expression of pro-inflammatory markers and cognitive performance in our transgenic Alzheimer Disease (AD)- like rats.LSD1 levels were measured at different ages (3, 6, 12 and 18 months old) in hippocampus of non-transgenic (APP-/-) and hemizygous (APP+/-) transgenic rats. Cognitive function was analyzed by Morris water maze, LSD1 levels and inflammatory protein markers expression were measured by western blot.In our transgenic rat model, hippocampal LSD1 levels begins to increase at very early stages of amyloid pathology, suggesting a possible epigenetic protective mechanism by which, transgenic rats, could trigger to preserve cognitive functions in response to the progressive β-amyloid accumulation. However, at 18 months of age, the excessive Aβ accumulation causes cognitive deficits not seen at previous ages or in non-transgenic age-matched controls. Our results suggest that increased LSD1 expression contribute to pro-inflammatory markers deregulation pointing LSD1 as a good candidate for clinical manipulation.