PMC:4195273 / 62941-66664
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4195273","sourcedb":"PMC","sourceid":"4195273","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4195273","text":"The hindbrain, as a region described to convey post-prandial satiety effects to the hypothalamus, has been considered a potential candidate site for CART action (Marty et al., 2007; Subhedar et al., 2014). Supporting evidence include the moderate CART expression in terms of both transcript levels and immunoreactivity in caudal brain areas such as the locus coeruleus, NTS, PBN and the inferior olive (Douglass et al., 1995; Koylu et al., 1998), accorded with the increased Fos-IR identified in the NTS and PBN following i.c.v. CART into the LV (Vrang et al., 1999b). Comparable to i.c.v. injections into the LV or 3V, hindbrain delivery of CART peptide through the 4th ventricle (4V) led to reduction in food intake and body weight in both fed and food-deprived rodents, whilst the hypophagic effects showed no specificity to nutrients from either chow, sucrose or a nutritionally complete liquid diet (Aja et al., 2001b, 2002; Zheng et al., 2001, 2002; Skibicka et al., 2009) (Table 1). Importantly, the extent of feeding inhibition appeared more potent with CART administered into the 4V compared with LV injections (Zheng et al., 2001), raising the speculation that the hindbrain may house the key mediator for the hypophagic effects of i.c.v. CART (Aja et al., 2001b). Foundation for the idea involved the postulate that the anorectic effects triggered by forebrain i.c.v. CART indeed reflected the outcome of CART diffusion into hindbrain sites via the cerebrospinal fluid (CSF) (Aja et al., 2001b). Surmised from the CART-IR observed in cell bodies and central terminals of vagal afferent neurons projecting to the GI tract, a potential functional role of CART in meal termination and satiety may effectuate at the level of the brainstem (Broberger et al., 1999; Zheng et al., 2002). In rat, vagotomy caused considerable reduction in CART mRNA expression in several CART fibers in the vagus nerve and viscero-sensory nodose ganglion (Broberger et al., 1999). To verify such proposition, cerebral aqueduct occlusion was performed with an aqueductal plug to interrupt the forebrain-hindbrain CSF flow, and CART was injected into the 3V or 4V (Aja et al., 2001b) (Table 1). Interestingly, cerebral aqueduct blockage markedly attenuated the anorectic effects of 3V CART, whilst suppression of food intake remained unchanged when receiving 4V CART injection, signifying the independence of hindbrain CART in producing anorexia (Aja et al., 2001b). In contrast, hindbrain processing may be required or responsible for mediating a hypophagic response following forebrain or interbrain i.c.v. CART, further reinforcing the role of the brainstem in manifesting CART-driven anorectic effects, as concordant with the aforementioned higher potency in feeding inhibition with 4V as opposed to forebrain or interbrain i.c.v. CART (Zheng et al., 2001). Specifically, on the assumption that the repressed ingestive behaviors following LV or 3V CART may attribute to hindbrain CART action, the observations resulted from obtrusion of CSF flow could offer a possible explanation for the opposite feeding effects of orexigenic and anorexigenic natures induced by direct hypothalamic subnuclei (Wang et al., 2000; Abbott et al., 2001; Kong et al., 2003; Smith et al., 2008; Hou et al., 2010) vs. hindbrain ventricular (Aja et al., 2001b, 2002; Zheng et al., 2001, 2002; Skibicka et al., 2009) CART administration respectively. Such phenomena promote reevaluation of the authenticity and proposed mechanisms involved in the hypophagia exhibited after forebrain ventricular CART detailed in other studies (Kristensen et al., 1998; Lambert et al., 1998; Vrang et al., 1999b; Larsen et al., 2000; Abbott et al., 2001; Aja et al., 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