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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the expression of apolipoprotein E (ApoE) mRNA in the cerebella of control and experimental rabbits fed with a cholesterol-rich diet for 8 weeks. Cholesterol-treated rabbits show a dramatic increase in serum cholesterol levels; however, no significant variations in the expression level of cerebellar ApoE mRNA were found in comparison to control rabbits. In addition, no differences were observed between control and hypercholesterolemic rabbits in the in situ hybridization pattern of ApoE mRNA on cerebellar cortex sections. ApoE mRNA was localized in astroglial processes associated with Purkinje cell bodies and dendrites, granule cell clusters, blood vessels and nerve fibers of the white matter. No expression of ApoE mRNA was observed in Purkinje and granule cell neurons. Polarized light examination of cryostat cerebellar sections revealed the absence of cholesterol-rich microglia/macrophage cells induced by the hypercholesterolemia. In this way, neither reactive microglial cells nor perivascular phagocytes were found by ultrastructural analysis in hypercholesterolemic conditions. The pattern of glial fibrillary acidic protein of the astroglial cells of the cerebellar cortex as well as their nuclear size were unchanged following cholesterol treatment, indicating the absence of astroglial activation induced by hypercholesterolemia. Our results suggest that cerebellar ApoE does not contribute to the general cholesterol homeostasis outside of the brain and supports the view that this cerebellar ApoE is involved in paracrine and autocrine functions particularly related with synapse turnover and membrane remodelling of astroglial cells.
Brain Res Mol Brain Res 1994 Jan
PMID:Apolipoprotein E expression in the cerebellum of normal and hypercholesterolemic rabbits. 816 12

An early pathological rise in extracellular K+ following acute hypoxia results in Cl- uptake into astrocytes through the Cl/HCO3- exchanger with an osmotic equivalent of water. This study addressed effects of the anion transport inhibitor, L-644,711, (5,6,-dichloro-2,3, 9,9a-tetrahydro-3-oxo-9a-propyl-1H-fluroen-7-yl)oxyacetic acid. Confluent primary cultures from neonatal guinea pigs, characterized as > 95% astrocytes with antiserum to glial fibrillary acidic protein, were manipulated by incubation in either basal buffer (BB) with the ionic composition of Dulbecco's minimum essential media (DMEM) or one with high extracellular K+ (HiK). Incubation in 27 or 60 mM Hik significantly reduced cell viability and precipitated a time-dose dependent increase in lactate dehydrogenase (LDH) efflux (30 min to 4 h). L-644,711 was not cytotoxic, and significantly inhibited HiK-stimulated LDH efflux. The optimal effective dose of L-644,711 for preventing injury in guinea pig astrocytes was 10(-11)M when administered simultaneously with the HiK paradigm or in reversing injury when administered 30 min after exposing cells to HiK. These findings indicate the potential usefulness of agents which modify ion transport processes in hypoxic-ischemic cerebral injury.
Mol Chem Neuropathol 1994 Jan
PMID:Loop diuretic derivative L-644,711 inhibits K(+)-stimulated cellular injury in neonatal guinea pig cortical astrocytes. 817 70

The distribution patterns of interleukin-1 beta (IL-1 beta) mRNA in various brain regions of saline- and kainic acid-treated rats were examined using in situ hybridization technique. In normal rat brain, the signals of IL-1 beta mRNA were observed in the cerebellar Purkinje cells and in dispersed cells in the hypothalamus. In the case of the kainic acid treatment, IL-1 beta mRNA was intensely induced in the olfactory bulb, lateral septum, thalamus, hypothalamus, polymorphic layers of hippocampus, piriform cortex, amygdala, entorhinal cortex and cerebral cortex at 2 h after the injection of kainic acid. In the hypothalamic region, we observed the induction of IL-1 beta mRNA around the paraventricular hypothalamic nucleus, anterior hypothalamic area, dorsomedial and ventromedial hypothalamic nucleus, mammillary regions and arcuate nucleus. The signal of IL-1 beta mRNA was still expressed 4 h after treatment with kainic acid, less intensely than at 2 h, but above the control level. In these regions, IL-1 beta mRNA was expressed mainly in the glial cells, which were densely stained by Cresyl violet and did not contain glial fibrillary acidic protein. These results suggest that IL-1 beta is produced by a certain type of glial cells, maybe microglia, and might have regulatory functions in the central nervous system.
Brain Res Mol Brain Res 1993 Oct
PMID:In situ hybridization study of interleukin-1 beta mRNA induced by kainic acid in the rat brain. 825 77

The denervation-induced changes on S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin immunoreactivity (IR) of the lamellar cells from cutaneous Meissner-like sensory nerve formations (SNF), or corpuscles, of the adult rat hind limb foot-pads were studied, using combined immunohistochemical and image analysis (optic microdensitometry) techniques. Animals were allowed to survive for 1, 3 and 7 days following sciatic and saphenous nerves transection. Lamellar cells of Meissner-like corpuscles displayed S-100 protein- and vimentin-IR, but not GFAP-IR. Denervation caused a marked time-dependent decrease of S-100 protein IR whereas vimentin-IR did not change or weakly increased. No positive GFAP-IR was observed in denervated SNF. These findings suggest that continuity of SNF with nerve fibers supplying them is necessary to maintain some of the immunohistochemical characteristics of the non-neuronal cells of SNF.
Cell Mol Biol (Noisy-le-grand) 1993 Nov
PMID:Effect of denervation on lamellar cells of Meissner-like sensory corpuscles of the rat. An immunohistochemical study. 826 64

Deposits of beta-amyloid are one of the main pathological characteristics of Alzheimer's disease. The beta-amyloid peptide (or beta/A4) constituent of these deposits is derived from the beta-amyloid precursor protein (beta APP), which is expressed in several isoforms. It has been suggested that an imbalance in the normal ratio between the Kunitz protease inhibitor (KPI)-containing beta APPs versus the non containing forms could result in altered processing of beta APP and progressive beta/A4 deposition. We have studied the expression of four beta APP isoforms in the rat brain after intracerebroventricular application of kainic acid. Increased levels of the KPI-containing beta APP and GFAP mRNAs were observed in tissues surrounding areas of neuronal damage. A parallel increase of beta APP and GFAP immunoreactivity was observed in reactive astrocytes in these areas. These results suggest that the normal ratio of beta APP isoforms may be profoundly altered as a result of neuronal damage and that non-neuronal cells may respond to neuronal injury by increased expression of the KPI-containing beta APP isoforms.
Brain Res Mol Brain Res 1993 Jan
PMID:Increased levels of the Kunitz protease inhibitor-containing beta APP mRNAs in rat brain following neurotoxic damage. 838 8

Amphetamines (AMPs) can cause long-term depletions in striatal dopamine (DA) and serotonin (5-HT), and these decrements are often accepted as prima facie evidence of AMP-induced damage to the dopaminergic and serotonergic projections to striatum. Rarely are indices linked to neural damage used to evaluate the neurotoxicity of the AMPs. Here, we determined the potential neurotoxic effects of two substituted AMPs, d-methylenedioxymethamphetamine (d-MDMA) and d-fenfluramine (d-FEN) in group-housed female C57BL6/J mice. Astrogliosis, assessed by quantification of glial fibrillary acidic protein (GFAP), was the main indicator of d-MDMA-induced neural damage. Assays of tyrosine hydroxylase (TH), DA, and 5-HT were used to determine effects on DA and 5-HT systems. Since AMPs are noted for both their stimulatory and hyperthermia-inducing properties, activity, as well as core temperature, was monitored in several experiments. To extend the generality of our findings, these same end points were examined in singly housed female C57bL6/J mice and in group-housed male C57BL6/J or female B6C3F1 mice after treatment with d-MDMA. Mice received either d-MDMA (20 mg/kg) (singly housed mice received dosages of 20, 30, or 40 mg/kg) or d-FEN (25 mg/kg) every 2 h for a total of four sc injections. d-MDMA caused hyperthermia, whereas d-FEN induced hypothermia. d-MDMA cause a large (300%) increase in striatal GFAP that resolved by 3 wk and a 50-75% decrease in TH and DA that was still apparent at 3 wk, d-FEN did not affect any parameters in striatum. d-MDMA is a striatal dopaminergic neurotoxicant in both male and female C57BL6/mice, as evidenced by astrogliosis and depletions of DA in this area in both sexes. The greater lethality to males suggests they may be more sensitive, at least to the general toxicity of d-MDMA, that females. d-MDMA (20 mg/kg) induced the same degree of damage whether mice were housed singly or in groups. Higher dosages in singly housed mice induced greater lethality, but not greater neurotoxicity. d-MDMA was also effective in inducing striatal damage in mice of the B6C3F1 strain. Significant increases in activity were induced by d-MDMA, and these increases were not blocked by pretreatment with MK-801, despite the profound lowering of body temperature induced by this combination. A lowering of body temperature, whether by a 15 degree C ambient temperature (approx 2 degree drop), pretreatment with MK-801 (1.0 mg/kg prior to the first and third d-MDMA injections; approx 5-6 degrees C drop) or restraint (approx 5-6 degrees C drop) was effective in blocking the neurotoxicity of d-MDMA in both C57BL6/J and B6C3F1. The stimulatory effects of d-MDMA appeared to have little impact on the neurotoxicity induced by d-MDMA or the protection conferred by MK-801. These data suggest that in the mouse, the neurotoxic effects of d-MDMA, and most likly other AMPs, are linked to an effect on body temperature.
Mol Neurobiol
PMID:The role of temperature, stress, and other factors in the neurotoxicity of the substituted amphetamines 3,4-methylenedioxymethamphetamine and fenfluramine. 856 61

14.3.3 protein, a brain-specific protein, is an activator of tyrosine and tryptophan hydroxylases, key enzymes for biosynthesis of dopamine and serotonin. In this article, we describe cloning of cDNA for human brain 14.3.3 eta chain and expression of 14.3.3 eta chain mRNA in some human cultured cells. The cloned cDNA is 1730 bp long and contains 191 bp of a 5'-noncoding region, the complete 738 bp of coding region, and 801 bp of a 3'-noncoding region, containing three polyadenylation signals. This cDNA encoded a polypeptide of 246 amino acids (M(r) 28,196). Furthermore, using in situ hybridization histochemistry, the expression of mRNA for this protein was examined in the rat central nervous system. In situ hybridization histochemistry indicated that 14.3.3 eta chain mRNA is detected not only in the monoamine-synthetic neurons, but also in other neurons in the discrete nuclei, which synthesize neither cathecholamine nor serotonin. Northern blot analysis demonstrated that the addition of methamphetamine into the cultured medium increased the mRNA level for 14.3.3 eta chain in U-251 cells, but did not increase that of GFAP.
Mol Neurobiol
PMID:The effect on methamphetamine on the mRNA level for 14.3.3 eta chain in the human cultured cells. 856 65

Intraperitoneal injections of the nicotinamide antagonist 6-amino-nicotinamide (6-AN) were used to determine if there are regional differences in putative glial energy metabolism between the developing and adult rat CNS. 6-AN shuts down the hexose monophosphate pathway, which is used preferentially by astrocytes and oligodendrocytes. These cells subsequently undergo cytotoxic edema and cell death. Adult rats and pups ranging in age from 7 to 31 d received a single injection of 6-AN and were sacrificed after 24 h. As demonstrated wit immunocytochemical staining for the astroglia-specific markers GFAP and S-100 beta, the 7-9-d-old animals exhibited a uniform appearance with edematous glial cells located throughout the CNS. However, with advancing age, a consistent pattern of progressively decreasing amounts of injured glia, which has not been previously described, occurred in cerebral and cerebellar structures. After 3 wk postnatal, the adult pattern was manifested in which glial degeneration occurred only in specific regions of the spinal cord, cerebellum, medulla, and thalamus, whereas the remainder of the CNS appeared normal. The results suggest the presence of heterogeneous populations of glia whose preferred use of the hexose monophosphate pathway is predicated on both the age of the animal and their location in the CNS.
Mol Chem Neuropathol 1995 Oct
PMID:Age-dependent susceptibility of CNS glial populations in situ to the antimetabolite 6-aminonicotinamide. 857 44

We have previously reported that Ser13 and Ser34 on glial fibrillary acidic protein (GFAP) in the cleavage furrow of glioma cells are phosphorylated during late mitotic phase (Matsuoka, Y., K. Nishizawa, T. Yano, M. Shibata, S. Ando, T. Takahashi, and M. Inagaki. 1992, EMBO (Eur. Mol. Biol. Organ.) J. 11:2895-2902). This observation implies a possibility that there is a protein kinase specifically activated at metaphase-anaphase transition. To further analyze the cell cycle-dependent GFAP phosphorylation, we prepared monoclonal antibodies KT13 and KT34 which recognize the phosphorylation of GFAP at Ser13 and Ser34, respectively. Immunocytochemical studies with KT13 and KT34 revealed that the GFAP phosphorylation in the cleavage furrow during late mitotic phase occurred not only in glioma cells but also in human SW-13 and mouse Ltk- cells in which GFAP was ectopically expressed, thus the phosphorylation can be monitored in a wide range of cell types. Furthermore, we detected kinase activity which phosphorylates GFAP at Ser13 and Ser34 in the lysates of late mitotic cells but not in those of interphase cells or early mitotic cells. These results suggest that there exists a protein kinase which is specifically activated at the transition of metaphase to anaphase not only in GFAP-expressing cells but also in cells without GFAP.
 ...
PMID:Detection of protein kinase activity specifically activated at metaphase-anaphase transition. 864 94

1. Wobbler mice suffer an autosomal recessive mutation producing severe motoneuron degeneration and dense astrogliosis, with increased levels of glial fibrillary acidic protein (GFAP) in the spinal cord and brain stem. They have been considered animal models of amyotrophic lateral sclerosis and infantile spinal muscular atrophy. 2. Using Wobbler mice and normal littermates, we investigated the effects of the membrane-active steroid Lazaroid U-74389F on the number of GFAP-expressing astrocytes and glucocorticoid receptors (GR). Lazaroids are inhibitors of oxygen radical-induced lipid peroxidation, and proved beneficial in cases of CNS injury and ischemia. 3. Four days after pellet implantation of U-74389F into Wobbler mice, hyperplasia and hypertophy of GFAP-expressing astrocytes were apparent in the spinal cord ventral and dorsal horn, areas showing already intense astrogliosis in untreated Wobbler mice. In control mice, U-74389F also produced astrocyte hyperplasia and hypertophy in the dorsal horn and hyperplasia in the ventral-lateral funiculi of the cord. 4. Given in vivo U-74389F did not change GR in spinal cord of Wobbler or control mice, in line with the concept that it is active in membranes but does not bind to GR. Besides, U-74390F did not compete for [3H]dexamethasone binding when added in vitro. 5. The results suggest that stimulation of proliferation and size of GFAP-expressing astrocytes by U-74389F may be a novel mechanism of action of this compound. The Wobbler mouse may be a valuable animal model for further pharmacological testing of glucocorticoid and nonglucocorticoid steroids in neurodegenerative diseases.
Cell Mol Neurobiol 1996 Feb
PMID:The 21-aminosteroid U-74389F increases the number of glial fibrillary acidic protein-expressing astrocytes in the spinal cord of control and Wobbler mice. 871 60


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