Relative contribution of brainstem afferents to the cocaine- and amphetamine-regulated transcript (CART) innervation of thyrotropin-releasing hormone synthesizing neurons in the hypothalamic paraventricular nucleus (PVN)

To determine the relative contribution of the brainstem to the CART innervation of the TRH neurons in the PVN, the major ascending brainstem axonal pathways to the PVN were unilaterally transected in the hypothalamus. After 2 weeks survival time, hypothalamic sections were prepared for immunocytochemistry. PNMT-IR axon density decreased 76.0 +/- 3.8% on the side of the knifecut compared to the contralateral side, demonstrating satisfactory disconnection of the ascending brainstem pathways. In contrast, the density of CART-IR axons in the PVN on the lesioned side was reduced by only 26.9 +/- 2.7%. Disconnection of brainstem pathways reduced the total number of TRH neurons contacted by CART from 99.4 +/- 0.9% on the intact side to 74.3 +/- 9.4% on the lesioned side, as well as the number of CART varicosities on the surface of TRH neurons from 6.0 +/- 0.9 to 2.3 +/- 0.4 CART-IR varicosities/cell. These data indicate that CART-IR neurons residing in the brainstem give rise to only approximately one third of the CART input to the PVN as a whole, but serve as a major source of the CART-IR innervation of hypophysiotropic TRH neurons.     

Hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons: histochemical relationship to thyrotropin-releasing hormone, melanin-concentrating hormone, orexin/hypocretin and neuropeptide Y

The tree shrew is a mammalian species, which is phylogenetically related to insectivores and primates. The aim of the present study was to investigate the distribution of dopamine receptor D1- and D2-like binding sites in the brain of this non-rodent, non-primate mammal. Using in vitro autoradiography and employing the radioligands [3H]-SCH23390 and [125I]-epidepride, dopamine receptors were mapped and quantified. Significant findings with regard to the D1-like binding pattern include the presence of a "patchy" binding in the striatum. In the cortex, D1-like binding sites were observed in both the superficial and the deep layers. In the hippocampal formation, D1-like binding sites were seen primarily in the CAI region and not in the dentate gyrus. These characteristics of the D1 pattern in the tree shrew brain are shared by cat and monkey and human brain, but not by rodent brain. Significant findings with regard to the D2-like binding pattern include the presence of D2-like binding in the claustrum. In addition, the striatum demonstrated "patchy" D2-like binding. These characteristics of the D2 pattern in the tree shrew brain are shared by cat and monkey and human brain, but not by rodent brain. On the other hand, the significant densities of D2-like binding sites in the glomerular layer of the tree shrew olfactory bulb is a finding that discriminates tree shrews from higher evolutionary species who lack such binding. Overall, the evidence coincides with the view that tree shrews are phylogenetically related to primates.     

Hypothalamic cocaine-amphetamine regulated transcript (CART) is regulated by glucocorticoids

Nicorandil, a clinically useful drug for the treatment of ischemic heart disease, has an anti-apoptotic effect in cardiomyocytes, and activation of mitochondrial ATP-sensitive potassium (mitoK_ATP) channels underlies this effect. Recently, several studies showed that nicorandil reduced brain injury in animal models of brain ischemia. Based on these facts, we hypothesized that nicorandil may have anti-apoptotic effects in neurons mediated by mitoK_ATP channels. We investigated the effect of nicorandil on apoptosis induced by oxidative stress using cultured cerebellar granule neurons. Nicorandil (100 μmol/l) significantly suppressed the number of cells with TUNEL-positive nuclei and the increase in caspase-3 activity induced by 20 μmol/l H₂O₂. An indicator dye for mitochondrial inner membrane potential (ΔΨ_m) revealed that nicorandil prevented the loss of ΔΨ_m induced by H₂O₂ in a concentration-dependent manner. These effects were abolished by 5-hydroxydecanoate (5HD; 500 μmol/l), a mitoK_ATP channel blocker. The present results showed that nicorandil has anti-apoptotic effects in neurons, at least in part, by preserving ΔΨ_m.