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The physiological signaling mechanisms that link glucose sensing to the electrical activity in metabolism-regulating hypothalamus are still controversial. Although ATP production was considered the main metabolic signal, recent studies show that the glucose-stimulated signaling in neurons is not totally dependent on this production. Here, we examined whether mitochondrial reactive oxygen species (mROS), which are physiologically generated depending on glucose metabolism, may act as physiological sensors to monitor the glucose-sensing response. Transient increase from 5 to 20 mmol/l glucose stimulates reactive oxygen species (ROS) generation on hypothalamic slices ex vivo, which is reversed by adding antioxidants, suggesting that hypothalamic cells generate ROS to rapidly increase glucose level. Furthermore, in vivo, data demonstrate that both the glucose-induced increased neuronal activity in arcuate nucleus and the subsequent nervous-mediated insulin release might be mimicked by the mitochondrial complex blockers antimycin and rotenone, which generate mROS. Adding antioxidants such as trolox and catalase or the uncoupler carbonyl cyanide m-chlorophenylhydrazone in order to lower mROS during glucose stimulation completely reverses both parameters. In conclusion, the results presented here clearly show that the brain glucosesensing mechanism involved mROS signaling. We propose that this mROS production plays a key role in brain metabolic signaling. Diabetes 55: 2084 -2090, 2006 E lucidating the signaling mechanisms by which cells sense nutrient or metabolic status, a vital process in energy homeostasis, is of prime importance. Glucose-sensing mechanisms have been mainly characterized in two tissues, both in the pancreas (at the ␤-cell level) and in the brain (the so-called "glucose-stimulated" or "glucose-inhibited" neurons) (1,2). The cellular and molecular mechanisms underlying such glucose responsiveness appear to share similarities in the two glucose responsive cells (i.e., transport and phosphorylation by GLUT2 and glucokinase, respectively) and the consequent closure of ATP-sensitive K ϩ channels (K ATP channels) and calcium influx (3-5). Although ATP production used to be considered the main metabolic signal, recent studies show that the glucose-excited signaling in pancreatic ␤-cells and neurons is not totally dependent on this production. Within the hypothalamus, a previous work showed that glucose challenge monitors K ATP closure independently of ATP level (6), and more recent data demonstrated that glucose-induced depolarization might occur through a new K ATP channel-independent mechanism, at least in some hypothalamic arcuate neurons (7). These studies suggest that ATP-independent intracellular signaling mechanisms leading to the stimulation of hypothalamic neurons by glucose might be present.Transient increase in glucose metabolism generates the key substrates NADH and FADH 2 for the mitochondria, and their use increases electron formation without modifying other complex constraints along the res...

A dysfunction of retinoid hippocampal signaling pathway has been involved in the appearance of affective and cognitive disorders. However, the underlying neurobiological mechanisms remain unknown. Hippocampal granule neurons are generated throughout life and are involved in emotion and memory. Here, we investigated the effects of vitamin A deficiency (VAD) on neurogenesis and memory and the ability of retinoic acid (RA) treatment to prevent VAD-induced impairments. Adult retinoid-deficient rats were generated by a vitamin A-free diet from weaning in order to allow a normal development. The effects of VAD and/or RA administration were examined on hippocampal neurogenesis, retinoid target genes such as neurotrophin receptors and spatial reference memory measured in the water maze. Long-term VAD decreased neurogenesis and led to memory deficits. More importantly, these effects were reversed by 4 weeks of RA treatment. These beneficial effects may be in part related to an up-regulation of retinoid-mediated molecular events, such as the expression of the neurotrophin receptor TrkA. We have demonstrated for the first time that the effect of vitamin A deficient diet on the level of hippoccampal neurogenesis is reversible and that RA treatment is important for the maintenance of the hippocampal plasticity and function.

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Background: The preservation of fish egg quality after ovulation-control protocols is a major issue for the development of specific biotechnological processes (e.g. nuclear transfer). Depending on the species, it is often necessary to control the timing of ovulation or induce the ovulatory process. The hormonal or photoperiodic control of ovulation can induce specific egg quality defects that have been thoroughly studied. In contrast, the impact on the egg transcriptome as a result of these manipulations has received far less attention. Furthermore, the relationship between the mRNA abundance of maternally-inherited mRNAs and the developmental potential of the egg has never benefited from genome-wide studies. Thus, the present study aimed at studying the rainbow trout (Oncorhynchus mykiss) egg transcriptome after natural or controlled ovulation using 9152-cDNA microarrays.