Neuroscience
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Oxytocin (OT) administration in the ventromedial hypothalamic nucleus (VMH) reduces chow intake. The nature of VMH OT's anorexigenic action remains unclear. Here we provide insight into neural mechanisms underlying VMH OT-driven anorexia by (a) identifying feeding-related brain sites activated by VMH OT injection; (b) measuring VMH OT receptor (OTr) mRNA changes in response to hunger and palatability; and (c) examining how VMH OT affects episodic sweet solution intake in sated and hungry rats. ⋯ OT acting in the VMH decreases intake driven by energy not by palatability, and it stimulates activity of hypothalamic sites controlling energy balance.
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Sirtuin 6 (SIRT6), a member of the sirtuin family of NAD(+)-dependent deacetylases, has been shown to produce beneficial effects in myocardial ischemia/reperfusion (I/R). However, the role of SIRT6 in cerebral I/R is largely unclear. In this study, we investigated the effects of SIRT6 overexpression in regulating I/R injury in a mouse cerebral I/R model in vivo and in oxygen-glucose-deprivation/reoxygenation (OGD/R)-stimulated neuro-2a neuroblastoma cells in vitro. ⋯ Moreover, in OGD/R-stimulated neuro-2A cells, SIRT6 overexpression produced similar protective effects to those induced by the antioxidant NAC, but no added benefits were detected when SIRT6 overexpression was used in combination with NAC (P > 0.05). These findings provide evidence that SIRT6 can protect the brain from cerebral I/R injury by suppressing oxidative stress via NRF2 activation. Thus, SIRT6 may serve as a potential therapeutic target for ischemic stroke.
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The Ventral Tegmental Area (VTA) contains a considerable population of rhythmically firing dopaminergic neurons, which are influenced by auto-inhibition due to extra-synaptic dopamine release resulting in volume transmission. Using a Multi-Electrode-Array we simultaneously recorded in vitro from multiple VTA dopamine neurons in the rat and studied their mutual interactions. We observed that the dopamine sensitivity (EC50) of the neurons (i.e. the relation between dopamine concentration and firing rate) was quite variable within the recorded population. ⋯ Highly sensitive neurons became followers (of the population rhythm), whereas less sensitive dopamine neurons played a more leading role. This was confirmed by the application of sulpiride which reduces the dopamine sensitivity of all neurons through competition and abolishes the structure in the interactions. These findings imply that therapeutics, which have an easy to understand effect on firing rate, could have a more complicated effect on the functional organization of the local VTA population, through volume transmission principles.
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Neurons of the Grueneberg ganglion (GG) in the anterior nasal region of mice respond to a small set of odorous compounds, including given dimethylpyrazines present in mouse urine. Consequently, mouse pups living in murine colonies are presumably commonly exposed to such GG-activating substances. Since stimulation of the GG elicits alarm and stress reactions in mice, the question arises whether such a GG activation potentially inducing stress could be reduced when pups might rather feel secure in the presence of their mother. ⋯ The attenuated chemosensory responses of GG neurons at 35 °C coincided with a reduced dimethylpyrazine-evoked activation of the glomeruli in the olfactory bulb innervated by GG neurons. The reduction in dimethylpyrazine-evoked GG responses by warm temperatures was positively correlated with exposure time, suggesting that warm temperatures might enhance desensitization processes in GG neurons. In summary, the findings indicate that warm temperatures similar to those in mouse nests in the presence of the dam attenuate GG activation by colony-derived odorants.
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The regions of the olfactory epithelium affected by hydrogen sulfide (H2S) toxicity in the rat present a striking similarity with the developmental olfactory zone 1 described in the mouse. This zone which is the only region containing neurons expressing NAD(P)H quinone dehydrogenase 1 (NQO1) is involved in complex behavioral responses in rodents, and other mammals, triggered by specific olfactory stimuli. We therefore sought to determine whether (1) olfactory neurons expressing NQO1 are located in the same regions in the rats and in the mice and (2) there is an overlap between olfactory neurons expressing this protein and those affected by the toxicity of H2S. ⋯ The degree of agreement or overlap between these two populations of neurons (necrosis vs. NQO1 expression) reached 80.2%. Although the underlying mechanisms accounted for the high sensitivity for NQO1 neurons -or the relative protection of non NQO1 neurons- to sulfide toxicity remain to be established, this observation is offering an intriguing approach that could be used to acutely suppress the pool of neural cells in olfactory zone I and to understand the mechanisms of toxicity and protection of other populations of neurons exposed to sulfide.