The Role of Central Insulin Resistance in Neuronal Synaptic Plasticity Associated with Neuropsychiatric Disorders.
Xue, Chang.
2016
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Abstract: Diabetes and insulin resistance have been linked to cognitive impairment, mood disorders, and increased risk of Alzheimer's Disease. The mechanisms by which type 2 diabetes influences depression and anxiety are not known, but insulin resistance is associated with increased inflammation and cytokine production in some brain regions. Furthermore, ablation of insulin receptor in catecholami... read morenergic neurons attenuates insulin-induced excitability in dopaminergic neurons, whereas insulin administration into the central nervous system (CNS) of rats has been shown to increase dopamine transporter protein expression. The latter is important because alterations in the activity of dopamine and/or serotonin systems have been linked to depression. It has been previously demonstrated that mice with a targeted deletion of insulin receptors (IR) in the whole brain (NIRKO mice, produced through crossing of IR-lox with Nestin-Cre mice, showed anxiety and depressive-like behaviors. They were also characterized by mitochondrial dysfunction specific to the brain with reduced mitochondrial oxidative activity, increased levels of lipid and protein oxidation, as well as altered dopamine turnover in the CNS. Using carbon fiber amperometry to measure electrically evoked dopamine release in real time in acute brain coronal slices, our results demonstrated a 409% decrease in the average width of the dopamine signal in the nucleus accumbens and a 4410% decrease in t1/2 (width at half height), resulting in a 3914% decrease in dopamine molecules released per stimulation in NIRKO mice (p
Thesis (M.S.)--Tufts University, 2016.
Submitted to the Dept. of Pharmacology & Experimental Therapeutics.
Advisors: Emmanuel Pothos, and Margery Beinfeld.
Keyword: Health sciences.read less - ID:
- pz50h7650
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