The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area. Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS. Orexin neurons are “multi-tasking” neurons regulating a set of vital body functions, including sleep/wake states, feeding behavior, energy homeostasis, reward systems, cognition and mood. Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions. A selective loss orexin neurons was found in narcolepsia, supporting the crucial role of orexins in maintaining wakefulness. In animal models, orexin deficiency lead to obesity even if the consume of calories is lower than wildtype counterpart. Reduced physical activity appears the main cause of weight gain in these models resulting in energy imbalance. Orexin signaling promotes obesity resistance via enhanced spontaneous physical activity and energy expenditure regulation and the deficiency/dysfunction in orexins system lead to obesity in animal models despite of lower calories intake than wildtype associated with reduced physical activity. Interestingly, orexinergic neurons show connections to regions involved in cognition and mood regulation, including hippocampus. Orexins enhance hippocampal neurogenesis and improve spatial learning and memory abilities, and mood. Conversely, orexin deficiency results in learning and memory deficits, and depression.

In the present study we used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model to analyze resveratrol neuroprotective effects. The MPTP-induced PD model is characterized by chronic inflammation, oxidative stress and loss of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). We observed that resveratrol treatment significantly reduced glial activation, decreasing the levels of IL-1β, IL-6 and TNF-α, as well as their respective receptors in the SNpc of MPTP-treated mice, as demonstrated by Western blotting, RT-PCR and quantitative PCR analysis. This reduction is related to possible neuroprotection as we also observed that resveratrol administration limited the decline of tyrosine hydroxylase-immunoreactivity induced in the striatum and SNpc by MPTP injection. Consistent with these data, resveratrol treatment up-regulated the expression of the suppressor of cytokine signaling-1 (SOCS-1), supporting the hypothesis that resveratrol protects DA neurons of the SNpc against MPTP-induced cell loss by regulating inflammatory reactions, possibly through SOCS-1 induction.

Microglia-mediated neuroinflammation has been described as a common hallmark of Parkinson's disease (PD) and is believed to further exacerbate the progressive degeneration of dopaminergic neurons. Current therapies are unable to prevent the disease progression. A significant association has been demonstrated between PD and low levels of vitamin D in patients serum, and vitamin D supplement appears to have a beneficial clinical effect. Herein, we investigated whether vitamin D administered orally in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced preclinical animal model of PD protects against glia-mediated inflammation and nigrostriatal neurodegeneration. Vitamin D significantly attenuated the MPTP-induced loss of tyrosine hydrlase (TH)-positive neuronal cells, microglial cell activation (Iba1-immunoreactive), inducible nitric oxide synthase (iNOS) and TLR-4 expression, typical hallmarks of the pro-inflammatory (M1) activation of microglia. Additionally, Vitamin D was able to decrease pro-inflammatory cytokines mRNA expression in distinct brain areas of the MPTP mouse. Importantly, we also assessed the anti-inflammatory property of vitamin D in the MPTP mouse, in which it upregulated the anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) mRNA expression as well as increasing the expression of CD163, CD206 and CD204, typical hallmarks of alternative activation of microglia for anti-inflammatory signalling (M2). Collectively, these results demonstrate that vitamin D exhibits substantial neuroprotective effects in this PD animal model, by attenuating pro-inflammatory and up-regulating anti-inflammatory processes.

Krill oil (KO) is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals.

No abstract