Journal of Obesity & Weight Loss Therapy
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Diabetes is one of the major risk factors for dementia. However, the molecular mechanism underlying the risk of diabetes to
dementia is largely unknown. Recent studies revealed that epigenetic modifications may play a role in the pathogenesis of
diabetes. We hypothesized that diabetes may cause epigenetic changes in the brain that may adversely affect synaptic function.
We found significant elevation in the expression of histone deacetylases (HDACs) class IIa in the brains of diabetic subjects
compared to control subjects, and these changes coincide with altered expression of synaptic proteins. In a mouse model of
diet-induced type II diabetes mellitus (T2DM), we found that, similar to humans, T2DM mice also showed increased expression
of HDAC IIa in the brain and these alterations were associated with increased susceptibility to oligomeric Aβ-induced synaptic
impairments in the hippocampal formation and eventually led to synaptic dysfunction. Pharmacological inhibition of HDAC
IIa was able to restore synaptic plasticity. Our study demonstrated that diabetes may induce epigenetic modifications affecting
neuropathological mechanisms in the brain leading to increased susceptibility to insults associated with neurodegenerative or
vascular impairments. Our study provides for the first time an epigenetic explanation for the increased risk of diabetic patients
to develop dementia.
Giulio Maria Pasinetti?s research on lifestyle factors and metabolic co-morbidities influencing clinical dementia, neurodegeneration and Alzheimer?s
disease has made him a pioneer in his field. He is the recipient of major awards such as The Alzheimer?s Association?s Zenith Award and the
Foundation Queen Sofia of Spain Research Center award on Alzheimer?s disease. He has received more than 30 grants and has published over
160 groundbreaking research articles. He is a Professor of neurology, psychiatry, neuroscience, and geriatrics and adult development, and is chair
of the Brain Institute Center of Excellence for Novel Approaches to Neurotherapeutics at Mount Sinai School of Medicine. He also serves as director
of the Basic and Biomedical Research and Training, Geriatric Research, Education and Clinical Center at the Bronx Veterans Affairs Medical Center.
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