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Hydroxylase Immunoreactivity (hydroxylase + immunoreactivity)
Selected AbstractsCannabinoid modulation of limbic forebrain noradrenergic circuitryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2010Ana F. Carvalho Abstract Both the endocannabinoid and noradrenergic systems have been implicated in neuropsychiatric disorders. Importantly, low levels of norepinephrine are seen in patients with depression, and antagonism of the cannabinoid receptor type 1 (CB1R) is able to induce depressive symptoms in rodents and humans. Whether the interaction between the two systems is important for the regulation of these behaviors is not known. In the present study, adult male Sprague,Dawley rats were acutely or chronically administered the CB1R synthetic agonist WIN 55,212-2, and ,2A and ,1 adrenergic receptors (AR) were quantified by Western blot. These AR have been shown to be altered in a number of psychiatric disorders and following antidepressant treatment. CB1R agonist treatment induced a differential decrease in ,2A- and ,1-ARs in the nucleus accumbens (Acb). Moreover, to assess long-lasting changes induced by CB1R activation, some of the chronically treated rats were killed 7 days following the last injection. This revealed a persistent effect on ,2A-AR levels. Furthermore, the localization of CB1R with respect to noradrenergic profiles was assessed in the Acb and in the nucleus of the solitary tract (NTS). Our results show a significant topographic distribution of CB1R and dopamine beta hydroxylase immunoreactivities (ir) in the Acb, with higher co-localization observed in the NTS. In the Acb, CB1R-ir was found in terminals forming either symmetric or asymmetric synapses. These results suggest that cannabinoids may modulate noradrenergic signaling in the Acb, directly by acting on noradrenergic neurons in the NTS or indirectly by modulating inhibitory and excitatory input in the Acb. [source] Changes in hyporesponsiveness to acute amphetamine and age differences in tyrosine hydroxylase immunoreactivity in the brain over adolescence in male and female ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2009Iva Z. Mathews Abstract We investigated hyposensitivity after amphetamine in early (postnatal Day 30; P30) and late (P45) adolescent rats compared to adults (P70) in experiment 1. Locomotor activity was measured for 1,hr after the first (acute) and second (24,hr later) injection of amphetamine (0.5 or 1.5,mg/kg). P30 and P45 rats were transiently hypoactive compared to adults, as indicated by reduced locomotor activity after acute amphetamine and enhanced activity after the second injection in adolescents only. In experiment 2, ovariectomy did not alter locomotor activity during habituation at any age compared to intact rats, and, as for intact adolescents, ovariectomized adolescents continued to be less active after amphetamine than adults, suggesting gonadal immaturity alone cannot account for age differences in experiment 1. However, ovariectomy attenuated the increase in activity after the second treatment. In experiment 3 involving untreated rats, tyrosine hydroxylase immunoreactivity was reduced in P30, P40, and P50 compared to P90 rats in the nucleus accumbens core and the medial prefrontal cortex. Thus, adolescents may have an increased threshold of behavioral activation that can be overcome with either a higher dose or with repeated amphetamine treatment, and may be related to changes in the dopamine system over development. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 417,428, 2009. [source] Increased osteopontin expression following intranigral lipopolysaccharide injection in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005Joanna Iczkiewicz Abstract Nigral cell death in Parkinson's disease is characterized by glial cell activation leading to inflammatory changes. Osteopontin (OPN) is a glycosylated phosphoprotein that is induced by inflammatory mediators and which we have previously shown to be present in the substantia nigra. However, the role of OPN in the nigral inflammation is not known. We now report on the effects of lipopolysaccharide (LPS)-induced glial cell activation in the substantia nigra of rats on OPN expression. LPS administration induced dopaminergic cell death as shown by reduced nigral tyrosine hydroxylase immunoreactivity. There was a corresponding time-dependent increase in both OPN mRNA, which was maximal at 48 h, and protein levels, which peaked at 72 h before returning to control levels by 120 h. This increase was accompanied by marked reactive gliosis as shown by increased OX-42, glial fibrillary acidic protein (GFAP) and ED1 immunoreactivity. OX-42-positive cells increased in a time-dependent manner, peaking at 72 h before returning to control levels at 120 h. Similarly, ED1-positive cells were present in their greatest numbers at 24 h but then gradually declined. These changes mirrored the alterations occurring in OPN protein and OPN mRNA, respectively. In contrast, GFAP-positive cells only started to increase in number at 120 h. Colocalization studies showed that OPN was present in both ED1- and OX-42-positive cells but not in GFAP-positive cells. These data confirm that intranigral injection of LPS induces a rapid and marked gliosis that accompanies the loss of tyrosine hydroxylase-positive neurones and suggest that, after glial cell activation, enhanced expression of OPN occurs linked to increased numbers of microglia and/or macrophages. This suggests that OPN may be functionally important in the control of inflammatory changes. [source] Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in Parkinson's disease and its model: neurotrophic implication in nigrostriatal neuronsJOURNAL OF NEUROCHEMISTRY, Issue 4 2005Yuriko Iwakura Abstract Epidermal growth factor (EGF) is a member of a structurally related family containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGF,) that exerts neurotrophic activity on midbrain dopaminergic neurons. To examine neurotrophic abnormality in Parkinson's disease (PD), we measured the protein content of EGF, TGF,, and HB-EGF in post-mortem brains of patients with Parkinson's disease and age-matched control subjects. Protein levels of EGF and tyrosine hydroxylase were decreased in the prefrontal cortex and the striatum of patients. In contrast, HB-EGF and TGF, levels were not significantly altered in either region. The expression of EGF receptors (ErbB1 and ErbB2, but not ErbB3 or ErbB4) was down-regulated significantly in the same forebrain regions. The same phenomenon was mimicked in rats by dopaminergic lesions induced by nigral 6-hydroxydopamine infusion. EGF and ErbB1 levels in the striatum of the PD model were markedly reduced on the lesioned side, compared with the control hemisphere. Subchronic supplement of EGF in the striatum of the PD model locally prevented the dopaminergic neurodegeration as measured by tyrosine hydroxylase immunoreactivity. These findings suggest that the neurotrophic activity of EGF is maintained by afferent signals of midbrain dopaminergic neurons and is impaired in patients with Parkinson's disease. [source] Nitration and Increased ,-Synuclein Expression Associated With Dopaminergic Neurodegeneration In Equine Pituitary Pars Intermedia DysfunctionJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2005D. McFarlane Abstract Equine pituitary pars intermedia dysfunction (PPID) is a spontaneously occurring progressive disease affecting aged horses and ponies. The pathogenesis of PPID is poorly understood, but the available evidence supports a loss of dopaminergic inhibition of the melanotropes of the pars intermedia. Horses with PPID have increased plasma concentrations of pars intermedia pro-opiomelanocortin-derived peptides that decrease in response to dopamine or dopamine agonist administration. Dopamine and dopamine metabolite concentrations are decreased in the pars intermedia of affected horses compared to age-matched control horses. Horses with disease that are treated with the dopamine agonist pergolide show improvement in clinical signs and normalisation of diagnostic test results. In the present study, immunohistochemical evaluation of pituitary and hypothalamic tissue demonstrated reduced tyrosine hydroxylase immunoreactivity in affected horses compared to age-matched and young controls, supporting the role of dopaminergic neurodegeneration in PPID. In addition, immunohistochemical evaluation revealed an increase in the oxidative stress marker, 3-nitrotyrosine and in nerve terminal protein, ,-synuclein that colocalised in the pars intermedia of horses with disease. These findings suggest a role for nitration of overexpressed ,-synuclein in the pathogenesis of neurodegeneration in PPID. [source] Severe generalized dystonia due to primary putaminal degeneration: Case report and review of the literature,MOVEMENT DISORDERS, Issue 3 2002Ruth H. Walker MB Abstract Putaminal lesions of a variety of etiologies may cause secondary dystonia. We report on a case of primary putaminal degeneration as a cause of severe childhood-onset generalized dystonia and review the literature of the pathology of dystonia. A 44-year-old patient with severe generalized childhood-onset dystonia and macrocephaly underwent neurological evaluation and neuropathological examination. Neurological examination was normal apart from dystonia and signs referable to prior cryothalamotomy. Workup for metabolic and genetic causes of dystonia was negative. Neuroimaging showed severe bilateral putaminal degeneration, which subsequently correlated with the neuropathological findings of gliosis, spongiform degeneration, and cavitation. The substantia nigra pars compacta contained a normal number of neurons but decreased tyrosine hydroxylase immunoreactivity. There were no histopathological markers of other metabolic or degenerative diseases. © 2002 Movement Disorder Society. [source] Aging of the nigrostriatal system in the squirrel monkeyTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2004Alison L. McCormack Abstract Increasing incidence of Parkinson's disease with advancing age suggests that age-related processes predispose the nigrostriatal dopaminergic system to neurodegeneration. Several hypotheses concerning the effects of aging on nigrostriatal neurons were assessed in this study using a non-human primate model. First, we examined the possibility that the total number of dopaminergic neurons decline in the substantia nigra as a function of age. Stereological counting based on both tyrosine hydroxylase immunoreactivity (TH-ir) and neuromelanin (NM) content revealed no difference in cell number between young, middle-aged and old squirrel monkeys. We then determined whether advancing age changed the relative proportion of neurons characterized by 1) TH-ir in the absence of NM, 2) the presence of both TH-ir and NM, or 3) NM without TH-ir. Indeed, a progressive age-related depletion of TH only cells was paralleled by an increase in NM only neurons. The possibility that these changes could underlie a functional impairment of the nigrostriatal system was supported by striatal dopamine measurements showing a decrease in older monkeys. Finally, we tested the hypotheses that aging may enhance cell vulnerability to injury and that different dopaminergic subpopulations display varying degrees of susceptibility. When monkeys were exposed to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, cell loss was markedly more pronounced in older animals, and the ranking of vulnerability was TH only < TH/NM < NM only cells. The data indicate that, even in the absence of an overall neuronal loss, changes in the characteristics of dopaminergic cells reflect functional deficits and increased vulnerability to injury with age. NM content appears to be an important marker of these age-related effects. J. Comp. Neurol. 471:387,395, 2004. © 2004 Wiley-Liss, Inc. [source] Regulation of sympathetic tone and arterial pressure by rostral ventrolateral medulla after depletion of C1 cells in ratTHE JOURNAL OF PHYSIOLOGY, Issue 1 2000Ann M. Schreihofer 1In this study we examined whether the rostral ventrolateral medulla (RVLM) maintains resting sympathetic vasomotor tone and activates sympathetic nerve activity (SNA) after the depletion of bulbospinal C1 adrenergic neurones. 2Bulbospinal C1 cells were destroyed (,84% loss) by bilateral microinjections (spinal segments T2 -T3) of an anti-dopamine-,-hydroxylase antibody conjugated to the ribosomal toxin saporin (anti-D,H-SAP). 3Extracellular recording and juxtacellular labelling of bulbospinal barosensitive neurones in the RVLM revealed that treatment with anti-D,H-SAP spared the lightly myelinated neurones with no tyrosine hydroxylase immunoreactivity. 4In rats treated with anti-D,H-SAP, inhibition of RVLM neurones by bilateral microinjection of muscimol eliminated splanchnic SNA and produced the same degree of hypotension as in control rats. 5Following treatment with anti-D,H-SAP the sympathoexcitatory (splanchnic nerve) and pressor responses to electrical stimulation of the RVLM were reduced. 6Treatment with anti-D,H-SAP also eliminated the majority of A5 noradrenergic neurones. However, rats with selective lesion of A5 cells by microinjection of 6-hydroxydopamine into the pons showed no deficits to stimulation of the RVLM. 7In summary, the loss of 84% of bulbospinal adrenergic neurones does not alter the ability of RVLM to maintain SNA and arterial pressure at rest in anaesthetized rats, but this loss reduces the sympathoexcitatory and pressor responses evoked by RVLM stimulation. The data suggest sympathoexcitatory roles for both the C1 cells and non-C1 cells of the RVLM and further suggest the C1 cells are critical for the full expression of sympathoexcitatory responses generated by the RVLM. [source] | |||||||||||||