Neuroscience
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Comparative Study
Nociceptin/orphanin FQ modulation of rat midbrain dopamine neurons in primary culture.
Previous microdialysis studies have identified a suppressive effect of the novel opioid peptide nociceptin (also known as orphanin FQ) on dopamine release from mesolimbic neurons. In order to further evaluate the locus of this action, we investigated nociceptin's action in an in vitro model system, namely midbrain dopamine neurons in primary culture. Immunohistochemical analysis revealed abundant tyrosine hydroxylase- and GABA-immunoreactive neurons, with a strong correlation between tyrosine hydroxylase content and basal endogenous dopamine release. ⋯ Application of the GABA-A antagonist, bicuculline, elevated extracellular dopamine concentrations but the dopamine release inhibiting property of nociceptin persisted in the presence of bicuculline. The NMDA receptor antagonist, D(-)-2-amino-5-phosphononpentanoic acid (AP-5) had no effect on basal dopamine release and failed to modify nociceptin's inhibitory effects. Thus, nociceptin potently modulates dopamine release from midbrain neurons most likely as a result of a direct suppression of dopamine neuronal activity.
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Comparative Study
Accumulation of Ym1/2 protein in the mouse olfactory epithelium during regeneration and aging.
A unique feature of the olfactory system is its efficiency to produce new neurons in the adult. Thus, destruction of the olfactory receptor neurons (ORNs) using chemical (intranasal perfusion with ZnSO4) or surgical (axotomy or bulbectomy) methods, leads to an enhanced rate of proliferation of their progenitors and to complete ORNs regeneration. The aim of our study was to identify new factors implied in this regenerative process. ⋯ In the olfactory mucosa of control mice, Ym1/2 was hardly detectable in young animals and became more and more abundant with increasing age. In injured and aged mice, Ym1/2 mainly accumulates in the cytoplasm of supporting cells as well as in other cells located throughout the olfactory epithelium. Our results suggest that Ym1/2 is involved in olfactory epithelium remodeling following several kinds of lesions of the adult olfactory mucosa and support the view of a critical role of inflammatory cues in neurodegeneration and aging.
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We sought to determine which medullary sympathetic premotor neurons mediate the cardiovascular and thermogenic effects resulting from activation of neurons in the dorsomedial hypothalamus (DMH) in urethane/chloralose-anesthetized, artificially ventilated rats. Unilateral disinhibition of neurons in the DMH with microinjection of bicuculline (2 mM, 30 nl) caused significant increases in brown adipose tissue sympathetic nerve activity (BAT SNA, +828+/-169% of control, n=16), cardiac SNA (+516+/-82% of control, n=16), renal SNA (RSNA, +203+/-25% of control, n=28) and, accompanied by increases in BAT temperature (+1.6+/-0.3 degrees C, n=11), end-tidal CO(2) (+0.7+/-0.1%, n=15), heart rate (+113+/-7 beats/min, n=32), arterial pressure (+19+/-2 mm Hg, n=32) and plasma epinephrine and norepinephrine concentrations. Inhibition of neurons in the rostral raphe pallidus (RPa) with microinjection of muscimol (6 mM, 60 nl) abolished the increases in BAT SNA and BAT temperature and reduced the tachycardia induced by disinhibition of DMH neurons. ⋯ Combined glutamic acid decarboxylase (GAD-67) immunocytochemistry and pseudorabies viral retrograde tracing from BAT indicated close appositions between GABAergic terminals and DMH neurons in sympathetic pathways to BAT. In conclusion, these results demonstrate the existence of a tonically active, GABAergic inhibitory input to neurons in the DMH and that blockade of this inhibition increases sympathetic outflow to thermogenic and cardiovascular targets by activating functionally specific populations of sympathetic premotor neurons: the excitation of BAT SNA and BAT thermogenesis is mediated through putative sympathetic premotor neurons in the RPa, while the activation in RSNA is dependent on those in RVLM. These data increase our understanding of the central pathways mediating changes in sympathetically mediated thermogenesis that is activated in thermoregulation, stress responses and energy balance.
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Glycinergic membrane responses have been described in cortical plate neurons (CPn) and Cajal-Retzius cells (CRc) during early neocortical development. In order to elucidate the functional properties and molecular identity of glycine receptors in these two neuronal cell types, we performed whole-cell patch-clamp recordings and subsequent single-cell multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analyses on visually identified neurons in tangential and coronal slices as well as in situ hybridizations of coronal slices from neonatal rat cerebral cortex (postnatal days 0-4). In both CPn and CRc the glycinergic agonists glycine, beta-alanine and taurine induced inward currents with larger current densities in CRc. ⋯ In situ hybridization histochemistry showed the expression of mRNAs for alpha(2) and beta subunits within the cortical plate and in large neurons of the marginal zone, while there were no signals for alpha(1) and alpha(3) subunits. In summary, these results suggest that CPn and CRc express glycine receptors with similar functional and pharmacological properties. The correlation of pharmacological properties and mRNA expression suggests that the glycine receptors in both cell types may consist of alpha(2)/beta heteromeric receptors.
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In a recent study, we have demonstrated that the dorsal root reflex (DRR)-mediated acute cutaneous neurogenic inflammation following intradermal injection of capsaicin (CAP) is sympathetically dependent and subject to modulation by peripheral alpha(1)-adrenoceptors. Postganglionic sympathetic neurons contain not only adrenergic neurotransmitters, but also non-adrenergic substances, including neuropeptide Y (NPY). In this study, we examined if peripheral NPY receptors participate in the flare following CAP injection. ⋯ In sympathetically intact rats, blockade of either peripheral NPY or Y(2) receptors with [D-Trp(32)]-NPY or BIIE0246 markedly reduced the flare induced by CAP injection, whereas blockade of peripheral Y(1) receptors by BIBP3226 did not obviously affect the flare. It is suggested that NPY is co-released with NE from the postganglionic sympathetic terminals to activate NPY Y(2) and alpha(1) receptors following CAP injection. Both substances are involved, at least in part, in modulation of the responses of CAP sensitive afferents thereby affecting their ability to evoke the release of inflammatory agents from primary afferents.