Neuroscience
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A high-fat diet (HFD) can increase hypothalamic galanin (GAL). GAL has recently been shown to inhibit opiate reward, which in turn, decreases cAMP response element-binding protein (CREB) in the nucleus accumbens (NAc). We hypothesized that injection of GAL into the paraventricular nucleus (PVN), or consumption of a HFD, would be associated with a decrease in NAc CREB. ⋯ Body weight, serum triglyceride and leptin levels were also raised in the chronic HFD-fed rats. These data suggest that PVN GAL or chronic intake of a HFD can decrease NAc pCREB. The implications of these findings may help to explain the lack of opiate-like withdrawal that has been reported in response to overeating a HFD, thereby providing a potential mechanism underlying behavioral differences seen with addiction-like overconsumption of different types of palatable foods.
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Reproductive success depends on a robust and appropriately timed preovulatory luteinizing hormone (LH) surge, which is induced by the activation of gonadotropin-releasing hormone (GnRH) neurons in response to positive feedback from increasing estrogen levels. Here we document an increase in postsynaptic GluR2-lacking Ca2+ -permeable AMPA-type glutamate receptors (CP-AMPARs) at synapses on GnRH neurons on the day of proestrus in rats, coincident with the increase in estrogen levels. Functional blockade of CP-AMPARs depressed the synaptic responses only on the day of proestrus and concomitantly attenuated the LH surge. Thus, the phasic synaptic incorporation of postsynaptic CP-AMPARs on GnRH neurons is involved in the generation of the LH surge.
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Because of its high oxygen demands, neural tissue is predisposed to oxidative stress. Here, our aim was to clarify the cellular localization of antioxidant enzymes in the trigeminal ganglion. We found that the transcriptional factor Sox10 is localized exclusively in satellite glial cells (SGCs) in the adult trigeminal ganglion. ⋯ Moreover, capsaicin induced the cellular demise of primary TRPV1-positive trigeminal ganglion neurons in a dose-dependent manner, and this effect was inhibited by a free radical scavenger and a pancaspase inhibitor. This study delineates the localization of antioxidative stress-related enzymes in the trigeminal ganglion and reveals the importance of the pivotal role of reactive oxygen species in the TRPV1-mediated caspase-dependent cell death of trigeminal ganglion neurons. Therapeutic measures for antioxidative stress should be taken to prevent damage to trigeminal primary sensory neurons in inflammatory pain disorders.
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γ-Hydroxybutyric acid (GHB) is used as an effective therapeutic for reducing the hypersomnolence and cataplexy (loss of motor control) of the sleeping disorder, narcolepsy, with an immediate pharmacologic behavioral action of inducing a natural sleep-like state. Despite its clinical use, few studies have examined the cellular actions of this drug on behavioral state-related neurons. Therefore, we monitored GHB-induced responses using calcium imaging within the laterodorsal tegmentum (LDT) and the dorsal raphe (DR), two pontine nuclei important in state and motor control. ⋯ Given the roles played by these nuclei, these actions are consistent with acute pharmacologic effects of GHB: hypotonia and promotion of sleep, including presence of REM, a sub-state of sleep. Differences in GHB-mediated calcium suggest differential regulation of calcium-dependent processes, which may also contribute to functioning of the LDT and DR in state and motor control and the therapeutic pharmacologic actions of GHB, which develop following chronic administration. These findings add to knowledge of cellular actions of GHB and it is hoped that, combined with findings from other studies examining GHB neurotransmission, these data can contribute to development of highly targeted therapeutics at the GABAB receptor for management of human disorders presenting with alterations in motor and arousal control.
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Tropisetron, a selective 5-HT3 receptor (5-HT3R) antagonist, has been widely used to counteract chemotherapy-induced emesis. New investigations described the immunomodulatory properties of tropisetron which may not be 5HT3R mediated. In the present study, we assessed the potential effects of tropisetron on an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). ⋯ Concurrent administration of tropisetron and mCPBG did not significantly alter the histological damage in the spinal cord. mCPBG had no effect on the mentioned parameters. Taken together, these findings indicate that tropisetron has considerable immunoregulatory functions in EAE and may be promising for the treatment of MS or other autoimmune and inflammatory diseases of the CNS. Furthermore, beneficial effects of tropisetron in this setting seem to be both receptor dependent and receptor independent in the early phase of the disease.