Kinson0 s illness; PTZ, pentylenetetrazole; ROS, reactive oxygen species; TCA, tricarboxylic acid cycle This can be an open-access report distributed below the terms with the Creative Commons Attribution-NonCommercial-No Derivative Functions License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and supply are credited. n Correspondence to: Lineu Prestes, 748, Cidade Universit ia, S Paulo, 05508-000, SP, Brazil. Tel.: ?55 1130912922. E-mail address: [email protected] (A.J. Kowaltowski).with the oxygen and 25 of glucose from these organisms. This energy consumption is essential to preserve ionic balance in neurons, make action potentials, produce post-synaptic currents and recycle neurotransmitters [6]. Given that metabolite diffusion in the blood is restricted by the brain lood barrier, the brain should synthesize its own neuroactive compounds for instance glutamate, aspartate, glycine or D-serine from glucose [71]. In addition, neurons are extremely susceptible to oxidative damage and glucose oxidation in the pentose phosphate pathway is essential to receive NADPH and regenerate decreased glutathione, which is important to preserve redox balance in the brain [12].Mal-PEG4-OH manufacturer All these characteristics make the brain very dependent on glucose and an organ exceptionally sensitive to power deficits. Additionally to its higher power expenditure, the brain is also accountable for directly sensing and integrating energetic cues which can be sent from peripheral tissues within the type of nutrients and2213-2317/ – see front matter 2014 The Authors. Published by Elsevier B.Fmoc-L-Lys (Boc)-OH manufacturer V.PMID:23819239 All rights reserved. http://dx.doi.org/10.1016/j.redox.2013.12.I. Amigo, A.J. Kowaltowski / Redox Biology two (2014) 296?Fig. 1. The brain as a master regulator of physique energy manage. The figure represents a simplified scheme of how the brain receives signals from peripheral tissues in the hypothalamus. Orexigenic (AgRP/NPY) and anorexigenic (POMC/CART) neurons in the arcuate nucleus (ARC) on the hypothalamus sense these as well as other cues, for example circulating blood glucose levels. These signals are additional integrated by interaction with other hypothalamic nuclei (LH–lateral hypothalamus; PVN–paraventricular nucleus) and finally project into the regions on the brain involved in the reward program, like the ventral tegmental location (VTA) as well as the nucleus accumbens in the striatum.hormones (see Fig. 1), orchestrating physiological and behavioural responses [31]. For that reason, the brain acts as a master regulator for energy balance within the organism, figuring out meals intake and expenditure, in the similar time as it could be the key power consumer with the physique and the organ most susceptible to oxidative harm. Dietary restriction prolongs lifespans in a wide variety of organisms, spanning from yeast to rodents. Extra importantly, animals not only live longer, but their wellness is enhanced as well as the appearance of aging markers delayed [39]. In spite of substantial interest in the effects of dietary limitation, the causes that underlie these beneficial effects are nevertheless incompletely understood, due both to physiological and methodological factors. Dietary restriction produces large-scale systemic effects, with predicted synergic interactions among tissues. As an example, reducing total caloric intake prevents the metabolic syndrome, which in turn is usually a threat factor for other pathological circumstances, for example stroke [41]. Hence, discriminating involving systemic and tissue-specific effects.