leptin and pimagedine

Consumption of poor nutrients diets is associated with fat tissue expansion and with a central and peripheral low-grade inflammation. In this sense, the microglial cells in the central nervous system are activated and release pro-inflammatory cytokines that up-regulate the inducible nitric oxide synthase (iNOS), promoting Nitric Oxide (NO) production. The excess of NO has been proposed to facilitate anxious states in humans and rodents. We evaluated whether consumption of a high-refined carbohydrate-containing diet (HC) in mice induced anxiety-like behavior in the Novelty Suppressed Feeding Test (NFST) trough facilitation of NO, in the prefrontal cortex (PFC) and hippocampus (HIP). We also verified if HC diet induces activation of microglial cells, alterations in cytokine and leptin levels in such regions. Male BALB/c mice received a standard diet or a HC diet for 3 days or 12 weeks. The chronic consumption of HC diet, but not acute, induced an anxiogenic-like effect in the NSF test and an increase in the nitrite levels in the PFC and HIP. The preferential iNOS inhibitor, aminoguanidine (50 mg/kg, i.p.), attenuated such effects. Moreover, microglial cells in the HIP and PFC were activated after chronic consumption of HC diet. Finally, the expression of iNOS in the PFC and TNF, IL6 and leptin levels in HIP were higher in chronically HC fed mice. Taken together, our data reinforce the notion that diets containing high-refined carbohydrate facilitate anxiety-like behavior, mainly after a long period of consumption. The mechanisms involve, at least in part, the augmentation of neuroinflammatory processes in brain areas responsible for anxiety control.

Topics: Adipose Tissue; Animals; Anxiety; Behavior, Animal; Dietary Carbohydrates; Disease Models, Animal; Guanidines; Hippocampus; Inflammation; Leptin; Male; Mice; Mice, Inbred BALB C; Nitric Oxide Synthase Type II; Nitrites; Prefrontal Cortex

Most people with diabetes develop severe complications of the autonomic nervous system; yet, the underlying causes of many diabetic-induced dysautonomias are poorly understood. Here we explore the idea that these dysautonomias results, in part, from a defect in synaptic transmission. To test this idea, we investigated cultured sympathetic neurons and show that hyperglycemia inactivates nAChRs through a mechanism involving an elevation in reactive oxygen species and an interaction with highly conserved cysteine residues located near the intracellular mouth of the nAChR channel. Consistent with this, we show that diabetic mice have depressed ganglionic transmission and reduced sympathetic reflexes, whereas diabetic mice expressing mutant postsynaptic nAChRs that lack the conserved cysteine residues on the alpha3 subunit have normal synaptic transmission in sympathetic ganglia and normal sympathetic reflexes. Our work suggests a new model for diabetic-induced dysautonomias and identifies ganglionic nAChRs as targets of hyperglycemia-induced downstream signals.

Topics: Acetylcholine; Adenoviridae; Age Factors; Aldehydes; Animals; Animals, Newborn; Body Temperature; Cells, Cultured; Cysteine; Diabetes Mellitus, Experimental; Disease Models, Animal; Enzyme Inhibitors; Excitatory Postsynaptic Potentials; Glucose; Guanidines; Heart Rate; Hypoglycemic Agents; Insulin; Leptin; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Oxidative Stress; Patch-Clamp Techniques; Reactive Oxygen Species; Receptors, Leptin; Receptors, Nicotinic; Sensory Receptor Cells; Superior Cervical Ganglion; Synaptic Transmission