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  • Plasticity of lumbosacral propriospinal neurons is associated with the development of autonomic dysreflexia after thoracic spinal cord transection. 18512692

    Complete thoracic (T) spinal cord injury (SCI) above the T6 level typically results in autonomic dysreflexia, an abnormal hypertensive condition commonly triggered by nociceptive stimuli below the level of SCI. Overexpression of nerve growth factor in the lumbosacral spinal cord induces profuse sprouting of nociceptive pelvic visceral afferent fibers that correlates with increased hypertension in response to noxious colorectal distension. After complete T4 SCI, we evaluated the plasticity of propriospinal neurons conveying visceral input rostrally to thoracic sympathetic preganglionic neurons. The anterograde tracer biotinylated dextran amine (BDA) was injected into the lumbosacral dorsal gray commissure (DGC) of injured/nontransected rats immediately after injury (acute) or 2 weeks later (delayed). At 1 or 2 weeks after delayed or acute injections, respectively, a higher density (P < 0.05) of BDA(+) fibers was found in thoracic dorsal gray matter of injured vs. nontransected spinal cords. For corroboration, fast blue (FB) or cholera toxin subunit beta (CTb) was injected into the T9 dorsal horns 2 weeks postinjury/nontransection. After 1 week transport, more retrogradely labeled (P < 0.05) DGC propriospinal neurons (T13-S1) were quantified in injured vs. nontransected cords. We also monitored immediate early gene c-fos expression following colorectal distension and found increased (P < 0.01) c-Fos(+) cell numbers throughout the DGC after injury. Collectively, these results imply that, in conjunction with local primary afferent fiber plasticity, injury-induced sprouting of DGC neurons may be a key constituent in relaying visceral sensory input to sympathetic preganglionic neurons that elicit autonomic dysreflexia after high thoracic SCI.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB350
    Nombre del producto:
    Anti-Enkephalin Antibody, clone NOC1

  • Interactions between neuropeptides and dopamine neurons in the ventromedial mesencephalon. 2417173

    Cholecystokinin (CCK), enkephalin, neurotensin (NT), substance P (SP) and substance K (SK) are five neuropeptides that exist in neuronal perikarya or fibers in the vicinity of the A10 dopamine neurons in the ventromedial mesencephalon. Based upon this anatomical proximity, many investigations have been evaluating the possibility that these peptides may influence the function of the A10 dopamine neurons. A variety of experimental techniques have been employed in this regard, including anatomical, electrophysiological, neurochemical and behavioral methodologies. Measurement of immunoreactive peptide levels with radioimmunoassay, and visualization of peptidergic neurons and fibers with immunocytochemistry has demonstrated not only that peptides exist in the vicinity of A10 dopamine neurons, but using double labeling techniques NT and CCK have been found to coexist with dopamine in the same neuron. Further, by combining retrograde tracing technique with immunocytochemistry, the origin of some peptidergic afferents to the ventromedial mesencephalon has been determined. With the exception of CCK-8, microinjection into the ventromedial mesencephalon of rats with all the peptides or potent analogues produces a dose-related increase in spontaneous motor activity. For SP, NT and enkephalin the motor response has been blocked by dopamine antagonists. Further, an increase in dopamine metabolism in mesolimbic dopamine terminal fields is produced concurrent with the behavioral hyperactivity. These data indicate that SP, SK, enkephalin and NT can activate dopamine neurons in the ventromedial mesencephalon. This postulate is supported by electrophysiological studies showing an excitatory action by iontophoretic administration of peptide onto dopamine neurons. However, in some studies, excitatory electrophysiological effects were not observed. While some observations are contradictory, sufficient data has accumulated that tentative postulates and conclusions can be made about how these peptides may influence the A10 dopamine neurons. Further, speculations are offered as to the role this modulatory action may play in the many behaviors and pathologies thought to involve these dopamine neurons.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo

  • Comparative immunocytochemical localization of putative opioid ligands in the central nervous system. 6274830

    We report a detailed comparative immunocytochemical mapping of enkephalin, CCK and ACTH/beta-endorphin immunoreactive nerves in the central nervous system of rat and guinea pig. Enkephalin immunoreactivity was detected in many groups of nerve cell bodies, fibers and terminals in the limbic system, basal ganglia, hypothalamus, thalamus, brain stem and spinal cord. beta-endorphin and ACTH immunoreactivity was limited to a single group of nerve cell bodies in and around the arcuate nucleus and in fibers and terminals in the midline areas of the hypothalamus, thalamus and mesencephalic periaqueductal gray with lateral extensions to the amygdaloid area. Cholecystokinin immunoreactive nerve fibers and terminals displayed a distribution similar to that of enkephalin in many regions; but striking differences were also found. An immunocytochemical doublestaining technique, which allowed simultaneous detection of two different peptides in the same tissue section, showed that enkephalin-, CCK- and ACTH/beta-endorphin-immunoreactive nerves although closely intermingled in many brain areas, occurred separately. The distributions of nerve terminals containing these neuropeptides showed striking overlaps and also paralleled the distribution of opiate receptors. This may suggest that enkephalin, CCK, ACTH and beta-endorphin may interact with each other and with opiate receptors.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo

  • The presence and absence of prosencephalic cell groups relaying striatal information to the medial and lateral thalamus in tenrec. 18510507

    Although there are remarkable differences regarding the output organization of basal ganglia between mammals and non-mammals, mammalian species with poorly differentiated brain have scarcely been investigated in this respect. The aim of the present study was to identify the pallidal neurons giving rise to thalamic projections in the Madagascar lesser hedgehog tenrec (Afrotheria). Following tracer injections into the thalamus, retrogradely labelled neurons were found in the depth of the olfactory tubercle (particularly the hilus of the Callejal islands and the insula magna), in subdivisions of the diagonal band complex, the peripeduncular region and the thalamic reticular nucleus. No labelled cells were seen in the globus pallidus. Pallidal neurons were tentatively identified on the basis of their striatal afferents revealed hodologically using anterograde axonal tracer substances and immunohistochemically with antibodies against enkephalin and substance P. The data showed that the tenrec's medial thalamus received prominent projections from ventral pallidal cells as well as from a few neurons within and ventral to the cerebral peduncle. The only regions projecting to the lateral thalamus appeared to be the thalamic reticular nucleus (RTh) and the dorsal peripeduncular nucleus (PpD). On the basis of immunohistochemical data and the topography of its thalamic projections, the PpD was considered to be an equivalent to the pregeniculate nucleus in other mammals. There was no evidence of entopeduncular (internal pallidal) neurons being present within the RTh/PpD complex, neuropils of which did not stain for enkephalin and substance P. The ventrolateral portion of RTh, the only region eventually receiving a striatal input, projected to the caudolateral rather than the rostrolateral thalamus. Thus, the striatopallidal output organization in the tenrec appeared similar, in many respects, to the output organization in non-mammals. This paper considers the failure to identify entopeduncular neurons projecting to the rostrolateral thalamus in a mammal with a little differentiated cerebral cortex, and also stresses the discrepancy between this absence and the presence of a distinct external pallidal segment (globus pallidus).
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB1975
    Nombre del producto:
    Anti-Enkephalin, Met Antibody

  • Neuropeptide Y and enkephalin immunoreactivity in retinorecipient nuclei of the hamster pretectum and thalamus. 9279004

    This investigation was stimulated by the historical confusion concerning the identity of certain pretectal nuclei and by large differences reported between species with respect to which nuclei receive retinal innervation. Subcortical visual nuclei were studied using immunohistochemistry to identify retinal projections labeled following intraocular injection of cholera toxin, b fragment. In addition, neuropeptide Y (NPY) or enkephalin (ENK) immunoreactive cells and fibers were also evaluated in the retinorecipient pretectal and thalamic areas. The results confirm the established view that the retina directly innervates the nucleus of the optic tract (NOT), posterior (PPT), and olivary pretectal (OPT) nuclei. However, the retina also innervates the hamster medial (MPT) and anterior (APT; dorsal division) pretectal nuclei, results not previously reported in rodents. A commissural pretectal area (CPT) sparsely innervated by retina is also described. The data show for the first time that the posterior limitans nucleus (PLi) receives a moderately dense, direct retinal input. The PLi does not project to the cortex and appears to be a pretectal, rather than thalamic, nucleus. All retinal projections are bilateral, although predominantly contralateral. The PLi contains a moderately dense plexus of NPY- and ENK-IR fibers and terminals. However, peptidergic fibers also traverse the ATP and connect with the dorsomedial pretectium. The OPT contains ENK- and NPY-IR neurons and fibers, but is specifically identifiable by a moderately dense plexus of ENK-IR terminals. Numerous ENK-IR neurons are found in the NOT and PPT. The latter also has moderate numbers of ENK-IR fibers and terminals, but few NPY-IR neurons or fibers. The MPT contains modest numbers of ENK-IR fibers. The APT has no NPY-IR neurons or terminals, but an occasional ENK-IR neuron is seen and there is sparse ENK-IR innervation. Peptidergic innervation of the visual nuclei does not appear to be derived from the retina. The results show a set of retinally innervated, contiguous nuclei extending from the thalamic ventrolateral geniculate nucleus dorsomedially to the midbrain CPT. These nuclei plus the superior colliculus comprise a dorsal "visual shell" embracing a central core of caudal thalamus and rostral midbrain.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB350
    Nombre del producto:
    Anti-Enkephalin Antibody, clone NOC1

  • Early direct and transneuronal effects in mice with targeted expression of a toxin gene to D1 dopamine receptor neurons. 10682709

    The neurochemical profile was examined at postnatal day 3-4 in mutant mice generated by in vivo Cre mediated activation of an attenuated diphtheria toxin gene inserted into the D1 dopamine receptor gene locus. An earlier study of this model had shown that D1 dopamine receptor, substance P and dynorphin were not expressed in the striatum. Quantitative in situ hybridization analysis showed an increase in D2 dopamine receptor and enkephalin messenger RNA expression. The nigrostriatal pathway in the mutant pups was intact with a normal number of dopaminergic neurons in the substantia nigra and the ventral tegmental area in addition to a normal pattern of striatal dopamine transporter and tyrosine hydroxylase immunoreactivity. Quantitative analysis of striatal dopamine transporter density using [3H]mazindol showed a reduction of 26% suggesting a degree of transneuronal down-regulation. There was also a 49% reduction of striatal GABA receptor binding and a 36% reduction of striatal muscarinic receptor binding in mutant pups. The number of healthy striatal neuropeptide Y-containing interneurons was also substantially down-regulated in the mutant striatum. In contrast, there was an increase in the number of striatal cholinergic interneurons. Down-regulated cortical GABA receptor and muscarinic receptor binding was also observed in addition to subtle morphological changes in the neuropeptide Y-expressing population of cortical neurons. The changes reflect the early cascade of events which follows the ablation of D1 dopamine receptor-positive cells. Although extensive changes in a number of striatal and cortical neurons were demonstrated, only subtle transneuronal effects were seen in the nigrostriatal pathway.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB369
    Nombre del producto:
    Anti-Dopamine Transporter Antibody, NT, clone DAT-Nt

  • Role of connexin-43 in protective PI3K-Akt-GSK-3β signaling in cardiomyocytes. 22505645

    Sarcolemmal connexin-43 (Cx43) and mitochondrial Cx43 play distinct roles: formation of gap junctions and production of reactive oxygen species (ROS) for redox signaling. In this study, we examined the hypothesis that Cx43 contributes to activation of a major cytoprotective signal pathway, phosphoinositide 3-kinase (PI3K)-Akt-glycogen synthase kinase-3β (GSK-3β) signaling, in cardiomyocytes. A δ-opioid receptor agonist {[d-Ala(2),d-Leu(5)]enkephalin acetate (DADLE)}, endothelin-1 (ET-1), and insulin-like growth factor-1 (IGF-1) induced phosphorylation of Akt and GSK-3β in H9c2 cardiomyocytes. Reduction of Cx43 protein to 20% of the normal level by Cx43 small interfering RNA abolished phosphorylation of Akt and GSK-3β induced by DADLE or ET-1 but not that induced by IGF-1. DADLE and IGF-1 protected H9c2 cells from necrosis after treatment with H(2)O(2) or antimycin A. The protection by DADLE or ET-1, but not that by IGF-1, was lost by reduction of Cx43 protein expression. In contrast to Akt and GSK-3β, PKC-ε, ERK and p38 mitogen-activated protein kinase were phosphorylated by ET-1 in Cx43-knocked-down cells. Like diazoxide, an activator of the mitochondrial ATP-sensitive K(+) channel, DADLE and ET-1 induced significant ROS production in mitochondria, although such an effect was not observed for IGF-1. Cx43 knockdown did not attenuate the mitochondrial ROS production by DADLE or ET-1. Cx43 was coimmunoprecipitated with the β-subunit of G protein (Gβ), and knockdown of Gβ mimicked the effect of Cx43 knockdown on ET-1-induced phosphorylation of Akt and GSK-3β. These results suggest that Cx43 contributes to activation of class I(B) PI3K in PI3K-Akt-GSK-3β signaling possibly as a cofactor of Gβ in cardiomyocytes.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • Ultrastructural analysis of the synaptic connectivity of TRPV1-expressing primary afferent terminals in the rat trigeminal caudal nucleus. 20878780

    Trigeminal primary afferents that express the transient receptor potential vanilloid 1 (TRPV1) are important for the transmission of orofacial nociception. However, little is known about how the TRPV1-mediated nociceptive information is processed at the first relay nucleus in the central nervous system (CNS). To address this issue, we studied the synaptic connectivity of TRPV1-positive (+) terminals in the rat trigeminal caudal nucleus (Vc) by using electron microscopic immunohistochemistry and analysis of serial thin sections. Whereas the large majority of TRPV1+ terminals made synaptic contacts of an asymmetric type with one or two postsynaptic dendrites, a considerable fraction also participated in complex glomerular synaptic arrangements. A few TRPV1+ terminals received axoaxonic contacts from synaptic endings that contained pleomorphic synaptic vesicles and were immunolabeled for glutamic acid decarboxylase, the synthesizing enzyme for the inhibitory neurotransmitter γ-aminobutyric acid (GABA). We classified the TRPV1+ terminals into an S-type, containing less than five dense-core vesicles (DCVs), and a DCV-type, containing five or more DCVs. The number of postsynaptic dendrites was similar between the two types of terminals; however, whereas axoaxonic contacts were frequent on the S-type, the DCV-type did not receive axoaxonic contacts. In the sensory root of the trigeminal ganglion, TRPV1+ axons were mostly unmyelinated, and a small fraction was small myelinated. These results suggest that the TRPV1-mediated nociceptive information from the orofacial region is processed in a specific manner by two distinct types of synaptic arrangements in the Vc, and that the central input of a few TRPV1+ afferents is presynaptically modulated via a GABA-mediated mechanism.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB1511

  • Photic induction of c-Fos in enkephalin neurons of the rat intergeniculate leaflet innervated by retinal PACAP fibres. 17503087

    The brain's biological clock, located in the suprachiasmatic nucleus (SCN), is synchronised with the cyclic environment by photic and non-photic cues. Photic information to the SCN is mediated by pituitary adenylate-cyclase-activating polypeptide (PACAP)-containing retinal ganglion cells (RGCs), whereas non-photic input originates primarily from neuropeptide Y (NPY) cells in the ipsilateral thalamic intergeniculate leaflet (IGL). RGCs also seem to project to the IGL, indicating a role for this structure in the integration of photic and non-photic inputs related to the resetting of the biological clock. In the present study, we have used anterograde tracing from both eyes, bilateral eye enucleation, double-immunofluorescence histochemistry, high-resolution confocal laser scanning microscopy and three-dimensional computer analysis to show that (1) PACAP-containing RGCs project to the IGL and are the only source for the PACAP-immunoreactive fibres in the IGL; (2) a few NPY-containing neurons in the IGL are innervated by PACAP-containing retinal nerve fibres and the contacts are both axodendritic and axosomatic; (3) most enkephalin-immunoreactive neurons in the IGL are innervated by PACAP-containing retinal afferents and the contacts are mainly axodendritic; (4) light stimulation at various time points activates (as evidenced by c-Fos induction) enkephalin-positive neurons but not NPY-immunoreactive neurons. The findings suggest that PACAP-immunoreactive retinal afferents in the IGL primarily innervate enkephalin-immunoactive neurons and that the enkephalin-containing neurons, which project locally and to the contralateral IGL, are activated by light independent of diurnal time.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB5026