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Cholecystokinin (CCK) is a well-known gut hormone that shows anorexigenic effects via action at peripheral and central receptors. CCK is also widely distributed throughout the mammalian brain and appears to function as a neurotransmitter and neuromodulator. The area postrema is one of the circumventricular organs, located on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle. Blood vessels in the area postrema lack a blood brain barrier, offering specific central neural elements unique access to circulating substances. Immunohistochemical studies show CCK-A receptors in the area postrema, and we reported CCK-sensitive area postrema neurons. However, the receptive mechanism of CCK in area postrema neurons still remains unexplained. We investigated the responses of area postrema neurons to agonists and antagonists of CCK receptors using whole cell and perforated patch-clamp recordings in rat brain slices. The application of CCK-8 elicited excitatory responses, such as increases in the frequency of mEPSCs (miniature excitatory postsynaptic currents), a shift toward larger amplitude mEPSCs, and increases in the frequency of action potentials. These changes were found mostly in cells not displaying the hyperpolarization-activated cation current (Ih), except for small excitatory changes in a minority of Ih-positive neurons. Tonic inward currents or an inhibitory response to CCK-8 were never seen. Analysis of the amplitude of mEPSCs before and after the administration of CCK-8 indicated the responses mediated via the presynaptic receptors. The effect of CCK-8 was abolished in the presence of CNQX (AMPA type glutamate receptor antagonist). In the presence of lorglumide (a selective CCK-A receptor antagonist), CCK-8-induced excitatory responses were inhibited. No cells responded to the administration of non-sulfated CCK-8 (CCK-8NS, a selective CCK-B receptor agonist). We conclude that CCK-8 exerts its action via presynaptic CCK-A receptors to facilitate glutamate release onto Ih-negative area postrema cells. [ABSTRACT FROM AUTHOR]

Intestinal motilin is known to stimulate gastrointestinal motility. Recently, it was shown that the motilin gene and the motilin receptor are expressed in various regions of the brain. We studied whether motilin can activate pathways in the rat hippocampus to stimulate gastric motility. Gastric motility was monitored in conscious rats, whereas extracellular electrical activity recordings of the hippocampus were performed on anaesthetized rats to measure the influence of microinjection of motilin and CCK-8 into the hippocampus and into the cerebral ventricles. We found that neurons in the CA3 region of the hippocampus are sensitive to gastric distension, and that injection of motilin into the hippocampus increased the amplitude of gastric contractions by 35.3±6.8%, while CCK-8 injection inhibited motility by −27.3±6.8%. The hippocampal motilin-induced stimulation of gastric motility (30.6±5.5%) was completely abolished by subdiaphragmal vagotomy (−2.8±4.4%) but unaffected by the intravenously applied receptor blockers atropine, phentolamine and propranolol. In vivo extracellular recordings of gastric distension-responsive CA3 neurons revealed that intracerebroventricular administration of motilin increased firing while CCK-8 inhibited firing. These opposite effects of motilin and CCK-8 fit with the nature of the actions of these gut–brain peptides on gastric motility. Our findings suggest that the stimulation of gastric motility by motilin administered in the hippocampus reflects the existence of a functional interaction between the hippocampus and a vago–vagus reflex running via a noncholinergic and nonadrenergic efferent pathway. [Copyright &y& Elsevier]

Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. Oxidative stress and mitochondrial dysfunction are widely accepted as central pathogenic mechanisms of MeHg-mediated neurotoxicity. Lycopene, a carotenoid compound, is a potent antioxidant with demonstrated neuroprotective properties in several experimental models of oxidative damage. The present study was designed to investigate whether lycopene could provide protective effects against MeHg-induced neurotoxicity in cultured rat cerebellar granule neurons (CGNs). The cultured CGNs were pretreated with different dose of lycopene for 2h, followed by the challenge with 500nM MeHg for 12h. It was found that MeHg exposure caused the loss of cell viability and the LDH release. Furthermore, we demonstrated that MeHg exposure significantly elevated intracellular reactive oxygen species generation and mitochondria-derived superoxide production, caused disruption of mitochondrial membrane potential and opening of mPTP, inhibited mitochondrial complex enzyme activities (complex III and complex IV), reduced ATP generation and decreased mtDNA copy numbers and mtDNA transcript levels. However, each of these oxidative damages was efficiently attenuated by lycopene pretreatment. Collectively, these results suggest that lycopene affords protection against MeHg-induced neurotoxicity in CGNs, and these beneficial effects of lycopene may be attributable to its roles in preventing mitochondrial dysfunction., (© 2013 Elsevier B.V. All rights reserved.)