LOCALIZATION OF NADPH CYTOCHROME-P450 OXIDOREDUCTASE IN RAT-BRAIN BY IMMUNOHISTOCHEMISTRY AND IN-SITU HYBRIDIZATION AND A COMPARISON WITH THE DISTRIBUTION OF NEURONAL NADPH-DIAPHORASE STAINING
cytochrome P450; inducible; l-arginine; messenger; metabolism; nervous-system; Neurosciences & Neurology; nitric-oxide synthase; p-450 reductase; parkinsons-disease; regional distribution; signal
An antibody to cytochrome P450 oxidoreductase, purified from rat liver, has been used for the immunohistochemical localization of cytochrome P450 oxidoreductase-like immunoreactivity in the rat central nervous system. The distribution of this immunoreactivity has been confirmed using in situ hybridization with specific cytochrome P450 oxidoreductase antisense DNA probes. Cytochrome P450 oxidoreductase immunoreactivity was detected in neurons and was found in some glial populations. Immunoreactivity and in situ messenger RNA signals were present in many forebrain areas including the olfactory bulb, in the cerebral cortex, caudate-putamen, globus pallidus, hypothalamus, thalamus and hippocampus. Cytochrome P450 oxidoreductase was also detected in the nucleus of the posterior commissure, superior colliculus, intermediate gray layer, periaqueductal gray and in the molecular, Purkinje and granular layers of the cerebellum. In the brain stem, cytochrome P450 oxidoreductase was detected in the substantia nigra, nucleus locus coeruleus and raphe nucleus. Western blotting studies revealed the brain immunoreactive protein has a mel, wt of approximately 72,000, as reported for cytochrome P450 oxidoreductase purified from rat brain microsomes. The distribution of cytochrome P450 oxidoreductase immunoreactivity was compared with the distribution of cells exhibiting NADPH diaphorase activity, which has been established as a histochemical marker for neuronal nitric oxide synthase, an enzyme which has a C-terminus with some structural similarity with cytochrome P450 oxidoreductase and catalyses a complex reaction resulting in the synthesis of nitric oxide from arginine. In general, cytochrome P450 oxidoreductase immunoreactivity and nitric oxide synthase diaphorase activity did not co-localize; however, some neuronal populations did express nitric oxide synthase and exhibit cytochrome P450 oxidoreductase immunoreactivity. Results of immunohistochemistry and in situ hybridization experiments suggest cytochrome P450 oxidoreductase is widespread in the rat central nervous system. The distribution pattern of cytochrome P450 oxidoreductase did not match with those of any one neurotransmitter; however, it did coincide with some brain regions known to harbour central catecholaminergic neurons. The general distribution of cytochrome P450 oxidoreductase was similar to the distribution reported for haeme oxygenase 2 and several cytochrome P450 enzymes. It is possible that malfunctions in cytochrome P450 enzyme systems and/or the haeme oxygenase 2 pathways, both of which involve cytochrome P450 oxidoreductase, may have implications in neurodegenerative diseases.
Norris P J; Hardwick J P; Emson P C
Neuroscience
1994
1994-07
Journal Article
<a href="http://doi.org/10.1016/0306-4522(94)90235-6" target="_blank" rel="noreferrer noopener">10.1016/0306-4522(94)90235-6</a>
Development of fusimotor innervation correlates with group Ia afferents but is independent of neurotrophin-3
deficits; Developmental Biology; expression; fusimotor innervation; growth factor; messenger-rna; mice; motor-neurons; muscle spindle; nervous-system; Neurosciences & Neurology; neurotrophin-3; proprioception; rat; transgenic mice
Fusimotor neurons, group Ia afferents and muscle spindles are absent in mutant mice lacking the gene for neurotrophin-3 (NT3). To partition the effect of Ia afferent or spindle absence from that of NT3 deprivation on fusimotor neuron development, we examined the fusimotor system in a mutant mouse (NesPIXpNT3) that lacks Ia afferents and spindles, but has normal or elevated tissue levels of NT3 during embryogenesis. Fusimotor fibers were absent in lumbar ventral spinal roots, and limb muscles were devoid of Ia afferents and spindles in adult NesPIXpNT3 mice. In contrast, no deficiency in motoneuron numbers was observed in the trigeminal nucleus which contains cell bodies of motor axons innervating muscles of mastication. Spindles and Ia afferents were also present in the masticatory muscles. Thus, the development and/or survival of fusimotor neurons correlates with the presence of Ia afferents and/or spindles, and not with the amount of NT3 in the spinal cord or muscle. (C) 1998 Elsevier Science B.V. All rights reserved.
Ringstedt T; Copray S; Walro J; Kucera J
Developmental Brain Research
1998
1998-12
Journal Article
<a href="http://doi.org/10.1016/s0165-3806(98)00146-1" target="_blank" rel="noreferrer noopener">10.1016/s0165-3806(98)00146-1</a>
Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson's disease
Signaling; Neuroprotection; MPTP; mice; Akt; 3; 2; 1-methyl-4-phenyl-1; 6-tetrahydropyridine; receptor; Neurosciences & Neurology; Endocrinology & Metabolism; nervous-system; plasma-membrane; estrogen-receptor-alpha; er-alpha; gender-differences; rat-brain; striatum; estrogen; ERK; estradiol; growth-factor-i; protein-coupled receptor-30; selective estrogen; SERMs; Substantia nigra
Studies with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson's disease have shown the ability of 17 beta-estradiol to protect the nigrostriatal dopaminergic system. This paper reviews the signaling pathways mediating the neuroprotective effect of 17 beta-estradiol against MPTP-induced toxicity. The mechanisms of 17 beta-estradiol action implicate activation of signaling pathways such as the phosphatidylinositol-3 kinase/Akt and the mitogen-activated protein kinase pathways. 17 beta-estradiol signaling is complex and integrates multiple interactions with signaling molecules that act to potentiate a protective effect. 17 beta-estradiol signaling is mediated via estrogen receptors, including GPER1, but others receptors, such as the IGF-1 receptor, are implicated in the neuroprotective effect. Glial and neuronal crosstalk is a critical factor in the maintenance of dopamine neuronal survival and in the neuroprotective action of 17 beta-estradiol. Compounds that stimulate GPER1 such as selective estrogen receptor modulators and phytoestrogens show neuroprotective activity and are alternatives to 17 beta-estradiol. (C) 2012 Published by Elsevier Inc.
Bourque M; Dluzen D E; Di Paolo T
Frontiers in Neuroendocrinology
2012
2012-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.yfrne.2012.02.003" target="_blank" rel="noreferrer noopener">10.1016/j.yfrne.2012.02.003</a>