Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transgenic mice were generated using a construct that encodes mouse polyoma virus large T antigen, one of three oncogenic products of the "early region" of the polyoma viral genome. Of 16 transgenic families developed, 1 was characterized by a neurologic disorder consisting of constant tremor and recurrent seizures. Morphologic analysis of the central nervous system (CNS) of affected transgenic mice included: classical light and electron microscopic examination; immunohistochemical assessment of the presence and localization of myelin-specific proteins, of the astrocyte marker glial fibrillary acidic protein, of the oligodendrocyte marker galactosyl cerebroside, and of large T; double immunolabeling of glial fibrillary acidic protein or galactosyl cerebroside and large T to identify the CNS cell type in which large T is expressed; and in situ hybridization to study myelin basic protein gene expression. Our results suggest that polyoma large T is expressed in astrocytes, possibly resulting in altered glial-glial interactions causing impaired oligodendroglial development and secondary dysmyelination. Transgenic oligodendrocytes exhibit features of immaturity, failing to myelinate axons properly and producing morphologic phenotypes of early stages of myelination, such as numerous mesaxonal profiles. Myelin proteins are markedly reduced in transgenic CNS, and myelin basic protein transcripts, while present, are generally decreased. We believe that expression of large T in astrocytes could influence the complex and dynamic interactions between astrocytes and oligodendrocytes, perhaps with regard to the molecular (trophic) signals in the local CNS environment, bringing about arrested oligodendroglial maturation and hypomyelination. This raises intriguing questions concerning the importance of glial-glial interactions in the CNS and the complex levels of control involved in biological expression of genetic information in glial cells.
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PMID:Transgenic mice expressing polyoma virus large T antigen in astrocytes develop severe dysmyelination of the central nervous system. 130 29

Four different human astrocytic cell lines established from either epilepsy surgical specimens or cerebral white matter obtained during thalamotomy for tremor in a patient with multiple sclerosis were characterized using morphologic analysis, ultrastructural attributes, growth characteristics, and immunocytochemical analysis. Immunocytochemical characterization of cultures indicated a mean of 84% of cells contained cytoplasmic glial fibrillary acidic protein (GFAP): to confirm that GFAP(+) cells also proliferated, bromo-deoxyuridine (BrdU) uptake was measured in cell line. Our method of simplified explant culture allows establishment of astrocytic cell lines from a variety of pathologic substrates using limited amounts of human material.
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PMID:Characterization of adult human astrocytes derived from explant culture. 196 82

A stationary tissue culture system for reaggregation cultures of rat brain cells is described. Aggregates were formed by placing cells at high concentration in liquid overlay cultures on a nonadherent nutrient agar surface. No physical stress in the form of rotation or shaking was applied to the aggregating cell population. Transmission electron microscopy and immunohistochemistry showed that the cells developed from homogeneously dispersed, immature cells in Day 4 aggregates, to mature astrocytes, oligodendrocytes, and neurons in Day 20 aggregates. Twenty days older aggregates had a tightly packed neuropil which was most prominent in a cell-sparse outer layer of the aggregates. When the aggregates were allowed to adhere to a substrate, both glial fibrillary acidic protein (GFAP) positive and negative cells were observed migrating out from the aggregates. Cells giving a positive reaction for neuron specific enolase (NSE) were also present. This reaggregation procedure, with transfer of selected brain cell aggregates into agar-coated multiwells is an alternative three-dimensional culture system which can be potentially useful in the study of morphogenesis and cell interactions in the nervous system.
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PMID:Reaggregation of fetal rat brain cells in a stationary culture system. I: Methodology and cell identification. 351 71

A three-year-old boy with a progressive history of headache, vomiting and ataxia in the course of 2 months, was admitted on August 1983, when he was lethargic. Neurological examination revealed dysphagia, scanning speech and tremor in the bilateral hand. CT scan showed a very large enhanced mass in the center of posterior fossa with central necrosis in it and the dilatation of whole ventricular system. Suboccipital craniectomy was immediately performed and the tumor that occupied the vermis and invaded into both cerebellar hemisphere was subtotally removed. Postoperative irradiation was well performed: 4140 rads to the whole brain and 3162 rads to the spinal cord. However, 5 months later, facial palsy in the left side and progressive ataxia became prominent. CT scan showed multiple enhanced masses in the left trigonum and right anterior horn of the lateral ventricles and in the left cerebellopontine angle. In spite of chemotherapy, the patient had a down-hill course, especially after the ventricular hemorrhage, and died on June 9th, 1984. Histologically, the tumor had a lobulated appearance with an aggregation of tumor cells encircled by vascular septae. The cells within lobules generally had vesicular nuclei, which were arranged in parallel row. Occasionally smaller hyperchromatic cells with scant cytoplasm were present along the vascular septae. Reticulin was present within the septa, but was not observed within the lobules. Scattered astrocytic cells and processes were identified within the lobules by the immunoperoxidase technique for GFAP. The fibrillary cytoplasmic processes within the lobules were stained by immunoperoxidase technique for neurofilament (68K).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of cerebellar neuroblastoma]. 361 40

Cultures consisting primarily of O-2A progenitor cells and immature oligodendrocytes with a few microglia and astrocytes were obtained by shaking primary cultures from neonatal rat brain after 12-14 days in vitro. Addition of 50 micrograms/ml exogenous Neu-NAc alpha 2-3Gal beta 1-4Glc beta 1-1'ceramide (GM3 ganglioside) to the cultures resulted in an increase in the number and thickness of cell processes that stained intensely for sulfatide and galactocerebroside (galC) in comparison to control cultures without added GM3. The treated cultures also contained fewer astrocytes than control cultures as revealed by immunostaining for glial fibrillary acidic protein (GFAP). Cells that immunostained for both GFAP and sulfatide/galC were very rare in control cultures but were frequently seen in the GM3-treated cultures, suggesting that these may represent cells changing their direction of differentiation away from type II astrocytes toward oligodendrocytes under the influence of GM3. These effects on the developing rat oligodendrocytes were specific for GM3 ganglioside and were not produced by adding GM1, GM2, GD3, or GD1a to the cultures. Lactosyl ceramide and neuraminyl lactose were also ineffective. When control cultures were initially plated on polylysine and incubated with [14C]galactose, GD3 was the principal labeled ganglioside. However, as the control cells differentiated over time in culture without the addition of exogenous GM3 and produced increasing amounts of myelin-related components, the incorporation of [14C]galactose into endogenous GM3 increased to become the predominant labeled ganglioside by 6 days after plating. Metabolic labeling of the GM3-treated oligodendrocytes with [14C]galactose revealed increased incorporation into galC and sulfatide in comparison to control cultures, but a decreased labeling of endogenous GM3. Similarly, incorporation of an amino acid precursor into the myelin-associated glycoprotein (MAG) was increased by GM3 treatment, but incorporation into myelin basic protein (MBP) was not affected. Although the overall effect of added GM3 was to decrease the phosphorylation of most proteins in the oligodendrocytes, including MBP, GM3 enhanced the phosphorylation of MAG. These findings indicate that GM3 ganglioside has an important role in the differentiation of cells of the O-2A lineage toward myelin production, since differentiation is associated with increased metabolic labeling of endogenous GM3 in control cultures and is enhanced by the addition of exogenous GM3.
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PMID:Differentiation of oligodendrocytes cultured from developing rat brain is enhanced by exogenous GM3 ganglioside. 752 87

The twitcher (twi/twi) is an authentic murine model of human globoid cell leukodystrophy (GLD), caused by a deficiency of galactosylceramidase. Similar to human GLD, the twitcher shows progressive deterioration of neurological function and its neuropathology is characterized by a collection of periodic acid-Schift stain (PAS)-positive macrophages in the areas of demyelination. However, there are some differences in the clinico-pathological aspects between human and murine GLD. We investigated the spacio-temporal progression of neuropathology in the twitcher from postnatal day (PND) 10 to 45. No clinical symptoms or neuropathological changes were apparent in twi/twi until PND 15. Generally, infiltration of macrophages, concomitant with myelin degeneration, was recognized in the cerebellar white matter and the brain stem after PND 20, then in cerebral white matter after PND 25, and in cerebral and cerebellar gray matter after PND 30. The demyelination was very severe in the radix of the 8th and the 5th cranial nerves. The neurological symptoms such as tremor, spasticity and cranial nerve dysfunction were well correlated with the progression of pathological changes. Demyelination progressed in an orderly fashion such that myelin degeneration began 10 to 20 days after the commencement of myelination in any of the given nerve fiber tracts. This suggests that there are no significant differences in the metabolism of galactocerebroside in the myelin and myelin-forming cells in individual nerve fiber tracts throughout the murine brain. Over-expression of glial fibrillary acidic protein was already present before the initiation of obvious demyelination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spacio-temporal progression of demyelination in twitcher mouse: with clinico-pathological correlation. 752 64

The spastic rat is a neurological mutant of the Han-Wistar strain with prominent spasticity, tremor, and ataxia. Neurodegeneration is found in the CA3 sector of the hippocampus and in Purkinje cells of the cerebellum. We examined the forebrain and cerebellum of spastic rats for glial reactions by using immunolabelling for the astrocytic marker, glial fibrillary acidic protein (GFAP). First, a map of the GFAP-distribution was made representing a systematic series of frontal sections in controls. Reactive astrocytes with increased GFAP should occur in the areas with established neuronal degeneration, but they could also demarcate further regions with pathology in this rat strain. Since the baseline levels of GFAP-immunoreactivity differ between brain regions, control rats and clinically normal littermates served as controls to judge relative increases in major structures. In the CA3 sector and hilus of the dorsal hippocampus, a massive gliosis was detected. In the cerebellum, a patchy increase of GFAP labelling in Bergmann glia was found. Further increases of GFAP-labelling in reactive astrocytes occurred in fiber tracts, the ventral thalamic nuclei, medial geniculate nuclei, pontine region and optic layer of the superior colliculus. Inconsistent changes were noted in cortex and pallidum. No defects of glial labelling or malformations in glial architectonics were found. The reactive changes of astroglial cells in hippocampus and cerebellum are in proportion to the neuronal degeneration. The glial reactions in the other brain regions possibly reflect a reaction to fiber degeneration and incipient neuronal degeneration or functional alterations of glial cells in response to neuronal dysfunction.
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PMID:Altered pattern of immunohistochemical staining for glial fibrillary acidic protein (GFAP) in the forebrain and cerebellum of the mutant spastic rat. 759 15

We have previously demonstrated that chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion to the substantia nigra (SN) and the locus coeruleus (LC) both produce a long-lasting neurotoxicity on dopamine (DA) and norepinephrine (NE) neurons in these two areas, respectively. In the present study, we further examined the toxicity of MPTP in these two areas by using the immunohistochemical method. We have also assessed the role of glia cells in the SN and LC in mediating the toxicity of MPTP. Immunohistochemical results have confirmed the direct toxicity of MPTP in the SN, as revealed by significant decreases of tyrosine hydroxylase (TH)-positive cells in the SN and TH-positive fibers in the striatum. The specific gliotoxin alpha-aminoadipic acid (alpha-AA), when administered to the SN at 48 h interval, partially antagonized DA depletions and behavioral deficits produced by chronic MPTP treatment. When alpha-AA was administered to the SN every 24 h, it completely abolished the toxicity of MPTP. On the other hand, chronic MPTP infusions to the LC significantly decreased DA-beta-hydroxylase-positive cells in this area. When alpha-AA was injected into the LC at 48 h intervals, it did not prevent depletions of NE in the LC and the hippocampus caused by chronic MPTP infusions. It did not protect against the behavioral deficits produced by MPTP, either. When alpha-AA was injected into the LC every 24 h, it only partially prevented the toxicity of MPTP on NE in the LC. It also partially prevented the motor-impairing effect of MPTP; however, it barely protected against MPTP's toxicity on NE in the hippocampus and it did not antagonize the stereotypy deficit produced by chronic MPTP, either. Phasic tremor and rigidity were observed following MPTP infusions to the SN and the LC every day, but these symptoms were less frequently observed during the later experimental stage. Serotonin measures were not significantly altered by these treatments throughout these experiments. Immunoblotting results of glial fibrillary acidic protein (GFAP), a marker protein of astrocytes, have confirmed proper lesions of astrocytes by alpha-AA. These results together suggest that chronic MPTP treatment exerts a direct and long-lasting toxicity on DA neurons along the nigrostriatal pathway and NE neurons along the coeruleus-hippocampal pathway. The neurotoxicity of MPTP is probably mediated through astrocytes in the SN, and may be partly mediated through astrocytes in the LC also. These results imply a role for dendritic uptake of DA and NE in these cell body regions. However, these findings also suggest the possibility of differential mechanisms of MPTP's toxicity in these two areas.
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PMID:Differential interactive effects of gliotoxin and MPTP in the substantia nigra and the locus coeruleus in BALB/c mice. 768 60

Cytokines are thought to be important mediators in physiologic and pathophysiologic processes affecting the central nervous system (CNS). To explore this hypothesis, transgenic mice were generated in which the cytokine interleukin 6 (IL-6), under the regulatory control of the glial fibrillary acidic protein gene promoter, was overexpressed in the CNS. A number of transgenic founder mice and their offspring exhibited a neurologic syndrome the severity of which correlated with the levels of cerebral IL-6 expression. Transgenic mice with high levels of IL-6 expression developed severe neurologic disease characterized by runting, tremor, ataxia, and seizure. Neuropathologic manifestations included neuro-degeneration, astrocytosis, angiogenesis, and induction of acute-phase-protein production. These findings indicate that cytokines such as IL-6 can have a direct pathogenic role in inflammatory, infectious, and neurodegenerative CNS diseases.
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PMID:Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. 769 79

We used two methods to examine altered patterns of gene expression in rat hippocampus in response to administered glucocorticoids: analysis of RNA in vitro translation products on 2-d gels and cloning of cDNAs from a rat hippocampal library by differential hybridization (+/- CORT). We determined that two of the CORT-responsive cDNA clones encoded the 35- and 50-kd RNA translation products and identified them as GPDH and GFAP, respectively, by sequence analysis. Cloned mRNAs that increased and decreased in response to CORT were determined to be under positive and negative regulation by glucocorticoids in intact rats. Despite their similarities in glucocorticoid response characteristics, we found three subsets of hippocampal mRNA responses to CORT and shaking stress which differ in temporal and level-dependent aspects of CORT regulation. In addition, GPDH gene expression represents a glucocorticoid-dependent stress response which is rapidly increased in a dose- and stressor-dependent manner. It is a candidate for a sensitive indicator of stress responsiveness in the brain as a function of neuroendocrine activity. Mechanisms of adaptation to stress in the brain are likely to involve responses that are both mediated by glucocorticoids and opposed by them. GFAP and TGF-beta 1 mRNA responses may be examples of the latter, since they are decreased in response to glucocorticoids, are under negative regulation by glucocorticoids in intact rats, and are increased in response to brain injury and disease and during aging. If these astrocytic and microglial responses are involved in cellular defense mechanisms in the brain, then their regulation by glucocorticoids would be important in maintaining and restoring cellular homeostasis in physiological and pathophysiological states. Future studies using these sensitive probes for glucocorticoid-regulated gene expression may identify new mechanisms by which the brain coordinates acute and chronic responses to stress and disease.
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PMID:Gene products of corticosteroid action in hippocampus. 782 72


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