Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to compare the recovery capacity of the nigrostriatal system between adult and old mice, MPTP hydrochloride was administered to 48 BL/C57 male mice, which were sacrificed 24 h or 10 d after the second dose. The animals were divided into four groups, based on age (adult or old) and moment of sacrifice (24 h or 10 d). The detailed morphology of the neurons and the cellular processes of the substantia nigra pars compacta and the striatum were studied using the Golgi method. Immunostaining with a polyclonal glial fibrillary acidic protein antiserum using the peroxidase-antiperoxidase technique was performed to study the glial response. Striatal catecholamines were determined to correlate the biochemical data with the morphological changes. Significant neuronal changes of cellular processes were observed in substantia nigra pars compacta from all MPTP-treated mice, consisting of swelling and distortion of cellular bodies, discontinuous thickness, and nodulations of dendrites with baded aspect. Axons showing focal swelling and nodulations were also found in the neuropil of silver impregnated striata. Marked gliosis with reactive astrocytes in substantia nigra and striatum from all the old treated mice was found. Recovery was only observed in adult mice sacrificed 10 d after withdrawal. At this time, all the old MPTP-treated mice showed marked neuronal changes and a persistent marked gliosis. As expected, 24 h after the MPTP treatment, a marked depletion of dopamine and its metabolites was found in all the animals; at 10 d, the depletion was partially reversed in the adult group. These data correlate well with the observed morphological changes. Our results suggest that, in mice, deterioration of dendritic and axonal neuropil constitutes a significant causal factor of the MPTP neurotoxicity. These features are related to the age of the animals and the integrity of the plasticity phenomena, which appear to be altered in old mice.
Mol Chem Neuropathol
PMID:Plasticity of the nigrostriatal system in MPTP-treated mice. A biochemical and morphological correlation. 810 34

The expression of mRNA encoding the growth associated protein, GAP-43, was investigated in rat hypoglossal motor neurons when the hypoglossal nerve was either resected or crushed unilaterally. For the detection of GAP-43 mRNA, a histochemical in situ hybridization method. using an alkaline phosphatase labeled probe, was used. The temporal profiles of GAP-43 mRNA expression were not identical following the two types of injuries. Increased expression in the hypoglossal nucleus contralateral to the injured nerve was observed from 1 day to 4-6 weeks after nerve crush, but lasted up to 7-8 weeks after resection. The magnitude and duration of increased GAP-43 mRNA expression were significantly greater following resection than crush injury. Local treatment with vinblastine, which is known to disturb the fast axonal flow by depolymerizing tubulin, also induced GAP-43 mRNA expression. The patterns of gene regulation following these nerve injuries may be due to the extent of nerve damage, to tubulin disturbance, or to some other factors derived from outside the nerve.
Brain Res Mol Brain Res 1994 Jan
PMID:GAP-43 (B50/F1) gene regulation by axonal injury of the hypoglossal nerve in the adult rat. 816 26

Calcineurin is a calmodulin-dependent serine-threonine phosphatase found in many cell types but most abundant in neurons. To determine its localization in developing neurons, dissociated cultures from embryonic day 15 rat cerebellum were analyzed immunocytochemically after treatment with cytoskeletal-disrupting drugs. During the initial outgrowth of neurites, calcineurin is enriched in growth cones where its localization depends upon the integrity of both microtubules and actin filaments. Treatment with cytochalasin shifts calcineurin from the growth cone to the neurite shaft, and with nocadozole calcineurin translocates to the cell body. Therefore calcineurin is well positioned to mediate interactions between cytoskeletal systems during neurite elongation. By 14 d in culture, when the neurons have developed extensive neuronal contacts and synapses are present, calcineurin is predominantly in the neurite shaft. Incubation of cultured cells with Cyclosporin A or a specific peptide, both of which selectively inhibit calcineurin's phosphatase activity, prevented axonal elongation. Because the microtubule-associated protein tau appears to play a key role in asymmetric neurite elongation, we examined modifications in its phosphorylation state resulting from calcineurin inhibition. In contrast to the normal development of cerebellar macroneurons in which reactivity with the phosphorylation-dependent antibody, tau-1, progressively increases, there was a persistent inhibition of tau-1 reactivity in cells exposed to Cyclosporin A. These findings suggest a role for calcineurin in regulating tau phosphorylation and possibly modulating other steps required for the determination of polarity.
Mol Biol Cell 1993 Dec
PMID:Calcineurin is associated with the cytoskeleton of cultured neurons and has a role in the acquisition of polarity. 816 6

The development of the nervous system in insects, as in most other higher animals, is characterized by the high degree of precision and specificity with which synaptic connectivity is established. Multiple molecular mechanisms are involved in this process. In insects a number of experimental methods and model systems can be used to analyze these mechanisms, and the modular organization of the insect nervous system facilitates this analysis considerably. Well characterized molecular elements involved in axogenesis are the cell-cell adhesion molecules that underlie selective fasciculation. These are cell-surface molecules that are expressed in a regional and dynamic manner on developing axon fascicles. Secreted molecules also appear to be involved in directing axonal navigation. Nonneuronal cells, such as glia, provide cellular and noncellular substrates that are important pathway cues for neuronal outgrowth. Once outgrowing processes reach their general target regions they make synapses with the appropriate postsynaptic cells. The molecular mechanisms that allow growth cones to recognize their correct target cells are essential for neuronal specificity and are being analyzed in neuromuscular and brain interneuron systems of insects. Candidate synaptic recognition molecules with remarkable and highly restricted expression patterns in the developing nervous system have recently been discovered.
Mol Neurobiol
PMID:Molecular correlates of neuronal specificity in the developing insect nervous system. 817 43

The binding of 14 lectins were performed on paraffin-embedded sections of the olfactory bulb of Triturus to identify specific glycoconjugates on the cell surface of primary olfactory projections. The histochemical lectin staining patterns indicate that the membrane of olfactory neurons terminating in the main olfactory bulb contained prevalently oligosaccharides with alpha-acetyl-D-galactosamine as terminal residues. In the accessory olfactory bulb, instead, the primary olfactory projections possess a high density of alpha-D-galactose as sugar residues. The selective lectin binding on the surface of primary olfactory axons suggests that specific cell surface glycoproteins may have a role in the axonal growth due to the continual cycle of proliferation and death of olfactory receptors.
Cell Mol Biol (Noisy-le-grand) 1993 Sep
PMID:Lectin histochemistry of cell-surface glycoconjugates in the primary olfactory projections of the newt. 822 74

1. The central nervous system (CNS) of the freshwater snail Lymnaea stagnalis contains several clusters of neuroendocrine cells, which synthesize neuropeptides that act as neurotransmitters, neurohormones, and/or neuromodulators, controlling a broad range of physiological processes. Using a protein chemical approach, we have previously characterized a peptide [named LYCP-A (Hoek et al., 1992], which is produced by the neuroendocrine light yellow cells (LYC), which are present as two clusters of endogenously bursting neurons in the visceral and right parietal ganglion, respectively. 2. A differential screening technique was used to isolate the cDNA that encodes the prohormone of LYCP-A. The prohormone appeared to contain three or four putative neuropeptides, one of which is LYCP-A. The organization of the identified prohormone resembles that of the histidine-rich basic peptide precursor previously identified in the R3-14 neurons of the marine snail Aplysia californica (Campanelli and Scheller, 1987). 3. In situ hybridization analysis indicates that the gene encoding the LYC prohormone is expressed in a subset of the LYC. The LYC release their peptides into the hemolymph from a neurohemal area, which is located around the CNS. In addition, the peptides are released from axonal branches in the aorta of the heart, suggesting a role in the regulation of cardiovascular functions.
Cell Mol Neurobiol 1993 Jun
PMID:The isolation of a cDNA encoding a neuropeptide prohormone from the light yellow cells of Lymnaea stagnalis. 824 89

While the involvement of the glutamate receptors in the hypothalamo-hypophyseal system has been clarified at the hypothalamic level, the existence of glutamate receptors in the pituitary gland has remained obscure. We investigated the localization of the glutamate receptors, the non-NMDA type receptor subunits (GluR1-4) in particular, by immunocytochemistry using specific antibodies. The antibodies specific to GluR1, GluR2/3 and GluR4 exhibited the characteristic localization of the receptor molecules in each lobe of the pituitary gland. GluR1- and GluR2/3-positive cells were identified in the anterior and intermediate lobe, and intense terminals of GluR4 and weak terminals of GluR2/3 were observed in the posterior lobe. Such immunoreactivity appeared to be at the axonal terminal of the neurosecretory magnocellular cells. This was confirmed by in situ hybridization histochemistry using specific oligodeoxynucleotide probes and by immunocytochemistry in the neurosecretory magnocellular neurons. The GluR4 mRNA-positive signal and GluR4 immunoreactivity were abundantly observed in magnocells of paraventricular and supraoptic nuclei. In addition to the positive fibers, some pituicytes in the posterior lobe exhibited GluR2/3 immunoreactivity. This suggests that pituicytes have non-NMDA type glutamate receptors. Thus, present study suggests that some anterior pituitary cells and pituicytes in the neural lobe are regulated by the glutamate.
Brain Res Mol Brain Res 1993 Aug
PMID:Characteristic localization of non-NMDA type glutamate receptor subunits in the rat pituitary gland. 841 73

In the adult rat hippocampus mRNA of F1/GAP-43, an axonal growth-associated protein, is highly expressed in pyramidal cells, but is absent in granule cells. To determine whether granule cells can be induced to express mRNA of F1/GAP-43, transcript levels were studied after limbic seizures, which can induce sprouting of granule cell mossy fibers. Seizure-inducing electrolytic lesions were made in the dentate gyrus hilus with stainless-steel electrodes and mRNA levels were measured in contralateral hippocampus by quantitative in situ hybridization. Induction of F1/GAP-43 mRNA expression was observed in granule cells at 24 h, but not at 6 or 12 h, after the hilar lesion. When equivalent sized hilar lesions were made with platinum electrodes, which do not induce seizures, no hybridization was apparent over the granule cells. Hybridization over granule cells had declined by 48 h post-lesion, but even at 10 days it was still slightly higher than in control rats. F1/GAP-43 mRNA expression was also increased 2-fold in CA1 pyramidal cells with peak expression at 48 h post-lesion. These are the first data to our knowledge that demonstrate that F1/GAP-43 gene expression can be altered in neurons located within the adult brain. Induction of F1/GAP-43 mRNA expression in the granule cells may be important for the sprouting of mossy fibers and could be triggered by the elevated levels of brain-derived neurotrophic factor in CA3 cells which precede the increased F1/GAP-43 gene expression in granule cells.
Brain Res Mol Brain Res 1993 Mar
PMID:Induction of F1/GAP-43 gene expression in hippocampal granule cells after seizures [corrected]. 851 May 1

The purpose of this study was to examine morphometric changes of myelinated fibers in early stages of experimental diabetes mellitus. Adult male Wistar rats aged 17 wk were used in this study. Diabetes mellitus was induced by streptozotocin. Samples of common peroneal nerve from diabetic rats (4 and 8 wk after induction of diabetes mellitus) and age-matched control animals were removed and processed. The semithin cross sections were stained with toluidine blue and used for myelinated fiber computer-aided morphometric analysis. There were no significant changes in diabetic animals after 4 wk duration of the disease. There was significant reduction in myelinated nerve fiber caliber in diabetic rats 8 wk after induction of diabetes as compared to age-matched controls. There was no significant reduction of axonal area in this group of diabetic rats, so diminution of fiber area was caused predominantly by reduction of myelin sheath area. The study demonstrates that the induction of diabetes mellitus in rat by streptozotocin is accompanied by early changes of the morphometric indices of myelinated nerve fibers of peripheral nerve.
Mol Chem Neuropathol
PMID:Quantitative analysis of myelinated nerve fibers of peripheral nerve in streptozotocin-induced diabetes mellitus. 853 23

1. The developing spinal cords of bullfrogs and transected cords of stage IV tadpoles were subjected to two-dimensional gel electrophoresis and histological analysis. During development, the level of actin, alpha-tubulin or beta-tubulin in the 7-10th spinal segments increased with time and reached a maximum around stage XIII followed by a decrease, as shown from quantitative assay on protein spots of 2-dimensional gels of cord homogenates. In contrast, the level of 68 kD neurofilament subunit (NF68) was low in tadpoles but high in frog. 2. Following a complete transection made at the level of the 8th spinal segment, the cord tissue of the lesion zone degenerated; regeneration from each cut end then occurred, which lengthened for approximate 0.35 mm by 28 days after transection. The content of actin, alpha-tubulin and beta-tubulin in the cord within 1-2 mm of the transection site was elevated to 124-192% of control values 7-28 days post-transection, whereas NF68 declined to near non-detectable extent. 3. The regeneration of each cord stump included outgrowth of neuroepithelial cells and nerve fibers, reconstituting a newly regenerated cord segment. Ultrastructural examination revealed that features of the regrowth of fibers and guidance of neuroepithelial cells to the axonal growth resembled that seen in the developing cord. Thus the biochemical and morphological data support that the regeneration of the nervous system recaptulates its developmental events, providing evidence for molecular mechanism underlying central axonal regeneration.
Cell Mol Neurobiol 1995 Aug
PMID:Relations between development and regeneration of tadpole spinal cord. 856 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>