Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The specific activities of glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) were measured in 6 regions of the central nervous system in young rats, following chronic postnatal administration of methylmercuric chloride. These rats exhibited signs of neurological impairment which included visual deficits, ataxia, spasticity and myoclonus. At the onset of neurological impairment, there was a significant reduction in GAD activity in the occipital cortex (43%), frontal cortex (37%) and caudate-putamen (42%). Preceding the onset of neurological impairment, diminished GAD activity was detected only in the occipital cortex. In the cerebellum, thalamus and spinal cord, GAD activities were normal throughout the experiment. No significant differences in ChAT activity were detected in any of the 6 regions. These results are consistent with a preferential involvement of GABAergic neurons in methylmercury-induced lesions of the cerebral cortex and neostriatum.
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PMID:Methylmercury poisoning of the developing nervous system in the rat: decreased activity of glutamic acid decarboxylase in cerebral cortex and neostriatum. 404 11

The Rett syndrome (RS) is a peculiar, sporadic, atrophic disorder, almost entirely confined to females. After the first six months of life there is developmental slowing with reduced communication and head growth for about one year. This is followed by a rapid destructive stage with severe dementia and loss of hand skills (with frequent hand wringing), apraxia and ataxia, autistic features and irregular breathing with hyperventilation. Seizures often supervene. Subsequently there is some stabilization in a pseudo-stationary stage during the preschool to school years, associated with more emotional contact but also abnormalities of the autonomic and skeletal systems. After the age of 15-20 years, a late motor deterioration occurs with dystonia and frequent spasticity but seizures become milder. RS has generally been considered an X-linked disorder in which affected females represent a new mutation, with male lethality. Linkage studies suggested a critical region at Xq28. In 1999, mutations in the gene MECP2 encoding X-linked methyl cytosine-binding protein 2 (MeCP2) were found in a proportion of Rett girls. This protein can bind methylated DNA. Analyses are leading to much further investigation of mutants and their effects on genes. Neuropathological and electrophysiological studies of RS are described. Description of neurometabolic factors includes reduced levels of dopamine, serotonin, noradrenaline and choline acetyltransferase (ChAT) in brain, also estimation of nerve growth factors, endorphin, substance P, glutamate and other amino acids and their receptor levels. The results of neuroimaging are surveyed, including volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET).
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PMID:Rett syndrome: review of biological abnormalities. 1125 89

Transient spinal cord ischemia may lead to a progressive degeneration of spinal interneurons and subsequently to increased hind limb motor tone. In the present work we sought to characterize the rigidity and spasticity components of this altered motor function by: i) tonic electromyographic activity measured in gastrocnemius muscle before and after ischemia, ii) measurement of muscle resistance during the period of ankle flexion and corresponding changes in electromyographic activity, iii) changes in Hoffmann reflex, and, iv) motor evoked potentials. In addition the effect of intrathecal treatment with baclofen (GABAB receptor agonist; 1 microg), nipecotic acid (GABA uptake inhibitor; 300 microg) and dorsal L2-L5 rhizotomy on spasticity and rigidity was studied. Finally, the changes in spinal choline acetyltransferase (ChAT) and vesicular glutamate transporter 2 and 1 (VGLUT2 and VGLUT1) expression were characterized using immunofluorescence and confocal microscopy. At 3-7 days after ischemia an increase in tonic electromyographic activity with a variable degree of rigidity was seen. In animals with modest rigidity a velocity-dependent increase in muscle resistance and corresponding appearance in electromyographic activity (consistent with the presence of spasticity) was measured during ankle rotation (4-612 degrees /s rotation). Measurement of the H-reflex revealed a significant increase in Hmax/Mmax ratio and a significant loss of rate-dependent inhibition. In the same animals a potent increase in motor evoked potential amplitudes was measured and this change correlated positively with the increased H-reflex responses. Spasticity and rigidity were consistently present for a minimum of 3 months after ischemia. Intrathecal treatment with baclofen (GABA B receptor agonist) and nipecotic acid (GABA uptake inhibitor) provided a significant suppression of spasticity, rigidity, H-reflex or motor evoked potentials. Dorsal L2-L5 rhizotomy significantly decreased muscle resistance but had no effect on increased amplitudes of motor evoked potentials. Confocal analysis of spinal cord sections at 8 weeks-12 months after ischemia revealed a continuing presence of ChAT positive alpha-motoneurons, Ia afferents and VGLUT2 and VGLUT1-positive terminals but a selective loss of small presumably inhibitory interneurons between laminae V-VII. These data demonstrate that brief transient spinal cord ischemia in rat leads to a consistent development of spasticity and rigidity. The lack of significant suppressive effect of dorsal L2-L5 rhizotomy on motor evoked potentials response indicates that descending motor input into alpha-motoneurons is independent on Ia afferent couplings and can independently contribute to increased alpha-motoneuronal excitability. The pharmacology of this effect emphasizes the potent role of GABAergic type B receptors in regulating both the spasticity and rigidity.
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PMID:Development of GABA-sensitive spasticity and rigidity in rats after transient spinal cord ischemia: a qualitative and quantitative electrophysiological and histopathological study. 1679 37