Long-term follow-up of pyridoxine-induced acute sensory neuropathy-neuronopathy.
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Action Potentials↗
Biomedical subjects
R L Albin
Publications and source records attributed to R L Albin.
Parasagittal zonation of GABA-B receptors in molecular layer of rat cerebellum.
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Animals↗
Feline subthalamic nucleus neurons contain glutamate-like but not GABA-like or glycine-like immunoreactivity.
The identity of the neurotransmitter of subthalamic nucleus neurons has not been definitively established. GABA, glycine, and glutamate have all been hypothesized to be the neurotransmitter of these neurons. Immunohistochemistry with 3 well characterized antisera against glutamate, GABA, and glycine were used to study feline subthalamic nucleus neurons. These neurons were found to contain intense glutamate-like but not GABA- or glycine-like immunoreactivity. The surrounding neuropil contained glutamate-like and GABA-like but not glycine-like immunoreactivity. These results support the hypothesis that subthalamic nucleus neurons are glutamatergic.
Animals↗
The functional anatomy of basal ganglia disorders.
Basal ganglia disorders are a heterogeneous group of clinical syndromes with a common anatomic locus within the basal ganglia. To account for the variety of clinical manifestations associated with insults to various parts of the basal ganglia we propose a model in which specific types of basal ganglia disorders are associated with changes in the function of subpopulations of striatal projection neurons. This model is based on a synthesis of experimental animal and post-mortem human anatomic and neurochemical data. Hyperkinetic disorders, which are characterized by an excess of abnormal movements, are postulated to result from the selective impairment of striatal neurons projecting to the lateral globus pallidus. Hypokinetic disorders, such as Parkinson's disease, are hypothesized to result from a complex series of changes in the activity of striatal projection neuron subpopulations resulting in an increase in basal ganglia output. This model suggests that the activity of subpopulations of striatal projection neurons is differentially regulated by striatal afferents and that different striatal projection neuron subpopulations may mediate different aspects of motor control.
Basal Ganglia↗
Tetrahydro-9-aminoacridine (THA) interacts with the phencyclidine (PCP) receptor site.
The effect of tetrahydro-9-aminoacridine (THA) and related compounds on ligand binding to the dissociative anesthetic (phencyclidine, PCP) receptor site was assessed using a rat brain homogenate assay. THA displaced the dissociative anesthetic ligand [3H]N-(1-[2-thienyl]cyclohexyl)3-4-piperidine [( 3H]TCP) binding with an IC50 of 26 microM. Other acridine derivatives displayed similar potency as displacers of [3H]TCP. Cholinesterase inhibitors and aminopyridines had IC50s equal to or greater than 100 microM. Saturation studies of [3H]TCP in the presence and absence of 30 microM THA revealed competitive inhibition with a K1 of 15 microM. The clinical pharmacology of THA suggests that it antagonizes the effects of dissociative anesthetics whereas in vitro, it behaves as a weak PCP agonist. THA may exert some of its clinical effects through interaction with the PCP receptor, and may have mixed agonist-antagonist properties.
Acridines↗
A new syndrome of axial muscle rigidity associated with etretinate therapy.
We report on three cases of a novel syndrome associated with treatment for psoriasis with the retinoid etretinate. The distinctive features of this syndrome include rigidity that is restricted to the axial muscles, impairment of neck extension greater than flexion, impairment of anteflexion at the waist, severe impairment of lateral flexion at both the waist and the neck, and, in one case, rigidity of proximal lower extremity muscles. Peripheral nerve block extinguished the lower extremity rigidity in one patient, and two patients had a favorable response to Sinemet. One patient had persistence of symptoms and findings 2 years after discontinuation of etretinate. The clinical features of this syndrome are consistent with an effect of etretinate on central, possible catecholaminergic neurons.
Adult↗
Chorea and dystonia: a remote effect of carcinoma.
A 45-year-old woman with an acquired multifocal neurologic syndrome, including chorea, dystonia, cerebellar dysfunction, multiple cranial neuropathies, and pure sensory neuropathy, was found at autopsy to have oat cell carcinoma. Neuropathologic examination revealed several features typically associated with remote effects of malignancy on the nervous system. We believe that this is the first described case of chorea as a remote effect of malignancy.
Carcinoma, Small Cell↗
Somatosensory phenomena in Huntington's disease.
Sensory symptoms are generally not associated with Huntington's disease (HD). We describe two patients with HD who had painful somatosensory symptoms. One patient also had auditory hallucinations. No other cause was found for these symptoms. Both patients also had significant depression and one patient committed suicide. Somatosensory symptoms may be a marker for depression in HD.
Adult↗
Glutamate transmission and toxicity in Alzheimer's disease.
1. Despite intensive research, the cause of Alzheimer's disease is unknown. 2. Glutamate is the major excitatory transmitter of the cerebral cortex and hippocampus and it appears to have an important role in learning and memory. In addition to its transmitter function, glutamate is a neurotoxin which has been implicated in the pathogenesis of a variety of neurodegenerative disorders. 3. Glutamate toxicity may play a role in the pathogenesis of Alzheimer's disease. 4. Disruption of glutamatergic neurotransmission may account, in part, for the learning and memory deficits of Alzheimer's disease. 5. Labeling of the glutamate receptor complex may allow in vivo diagnosis by positron emission tomography. 6. Glutamate receptor ligands may provide a means of therapeutic intervention in Alzheimer's disease.
Alzheimer Disease↗
Differential loss of striatal projection neurons in Huntington disease.
Huntington disease (HD) is characterized by the loss of striatal projection neurons, which constitute the vast majority of striatal neurons. To determine whether there is differential loss among different populations of striatal projection neurons, the integrity of the axon terminal plexuses arising from the different populations of substance P-containing and enkephalin-containing striatal projection neurons was studied in striatal target areas by immunohistochemistry. Analysis of 17 HD specimens indicated that in early and middle stages of HD, enkephalin-containing neurons projecting to the external segment of the globus pallidus were much more affected than substance P-containing neurons projecting to the internal pallidal segment. Furthermore, substance P-containing neurons projecting to the substantia nigra pars reticulata were more affected than those projecting to the substantia nigra pars compacta. At the most advanced stages of the disease, projections to all striatal target areas were depleted, with the exception of some apparent sparing of the striatal projection to the substantia nigra pars compacta. These findings may explain some of the clinical manifestations and pharmacology of HD. They also may aid in identifying the neural defect underlying HD and provide additional data with which to evaluate current models of HD pathogenesis.
Adolescent↗
Acute sensory neuropathy-neuronopathy from pyridoxine overdose.
We report two patients who developed an acute, profound, and permanent sensory deficit after treatment with massive doses of parenteral pyridoxine. Aside from rapid onset, their clinical picture resembles that described in chronic pyridoxine neurotoxicity. It also is consonant with experimental models of acute pyridoxine intoxication and is probably secondary to a sensory ganglion neuronopathy. These patients also had transient autonomic dysfunction, mild weakness, nystagmus, lethargy, and respiratory depression. These previously undocumented features may be attributable to either the preservative used in the parenteral pyridoxine preparation or to the exceptionally high doses of pyridoxine these patients received.
Acute Disease↗
Increased muscle tone during etretinate therapy.
A 40-year-old man with severe psoriasis developed painless muscle stiffness coinciding with four successive courses of etretinate therapy. Peripheral nerve block extinguished the increased muscle tone. Our patient's symptoms resembled those of the stiff-man syndrome. Increased muscle tone is a potential side effect of etretinate treatment and must be distinguished from the common musculoskeletal symptoms observed in patients taking retinoid therapy.
Adult↗
Age-related decrease in GABAB receptor binding in the Fischer 344 rat inferior colliculus.
Quantitative receptor autoradiography was used to assess GABAB receptor binding in three primary subdivisions of the inferior colliculus (IC): dorsal cortex (DCIC), external cortex (ECIC), and the central nucleus (CIC) of 3-, 18-20-, and 26-month-old Fischer 344 rats. GABAB binding sites were localized using [3H]GABA in the presence of a saturating concentration of isoguvacine, a selective GABAA receptor agonist, to displace [3H]GABA bound to GABAA receptor sites. In the three IC subdivisions examined, GABAB receptor binding was significantly reduced in 26-month-old rats when compared to 3-month-old rats (DCIC, -44%; ECIC, -36%; CIC, -32%; p < 0.05). For comparison, GABAB binding was determined in the portion of cerebellum located in the recess of the IC. In the molecular layer of this region, there was no statistically significant differences in receptor binding between 3, 18-20-, and 26-month-old rats. In addition, there was not a significant age-related change in the cross-sectional area of the IC. These findings provide additional evidence to support the existence of selective age-related changes in GABA neurotransmitter function in the rat IC.
Aging↗
GABAB binding sites in early adult and aging rat brain.
The effect of aging on GABAB binding was investigated in rat brain. Receptor autoradiography was used to investigate both GABAB and GABAA binding at 2 months, 3 months, 13 months, and 23 months. GABAB binding decreases significantly between 2 months and 23 months of age, as does GABAA binding, with was investigated in rat brain. Receptor autoradiography was used to investigate both GABAB and GABAA binding at 2 months, 3 months, 13 months, and 23 months. GABAB binding decreases significantly between 2 months and 23 months of age, as does GABAA binding, with the greatest decrease between 2 and 3 months. The decrease in GABAB binding appears to be due to a decrease in binding site affinity rather than a decrease in receptor density. The noncompetitive GABAB antagonist zinc, the competitive GABAB antagonist CGP 35348, and the guanyl nucleotide analogue GTP-gamma-S all inhibit GABAB binding identically in 2 month and 23 month brain. These data indicate subtle age-related changes in the GABAB binding in early adult life but little change with senescence.
Aging↗
Acute dyskinesias in young asthmatics treated with theophylline.
Two young children, 5 and 30 months of age, developed acute transient dyskinesias. The novel features of these patients were classic orobuccal-lingual dyskinesias, their young ages, and the association with asthma and theophylline. The movements resembled tardive dyskinesias of older patients on neuroleptics, but neither patient had any exposure to neuroleptic drugs. Choreiform movements were moderately severe and remitted several hours after discontinuation of theophylline or over days in the patient who remained on the drug. No symptomatic treatment of dyskinesia was required. Both infants otherwise had normal neurologic examinations with no clinical evidence of meningoencephalitis, seizures, or stroke. Both infants required hospitalization for respiratory distress, but not intensive care. The highest theophylline levels measured in these patients were 22 and 25 micrograms/ml and levels determined closest to the appearance of dyskinesias were lower. Urine toxicology screen for other drugs and routine blood work were normal. The infants, examined subsequently for 1 1/2-2 years for asthma, have demonstrated no reappearance of dyskinesias or other neurologic abnormalities. We propose an interaction of theophylline, hypoxemia, or other factors related to asthma in the pathophysiology of reversible dyskinesia in our patients.
Aminophylline↗
Excitatory and inhibitory amino acid neurotransmitter binding sites in the cerebellar cortex of the pigeon (Columba livia).
We used receptor autoradiography to determine the distribution of excitatory and inhibitory amino acid neurotransmitter binding sites in the cerebellar cortex of the pigeon (Columba livia). alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainate and metabotropic binding sites had highest levels in the molecular layer. N-methyl-D-aspartate binding sites, assayed with both [3H]glutamate under selective conditions and with [3H]glycine binding to the associated strychnine-insensitive glycine site, had highest levels in the granule cell layer. There was little specific binding of the non-competitive N-methyl-D-aspartate antagonist, [3H]MK-801. The level of gamma-aminobutyric acid (GABA)-A binding sites was higher than GABA-B binding sites in both molecular and granule cell layers with the highest level of GABA-A sites in the granule cell layer. The highest level of GABA-B binding sites was in the molecular layer. [3H]Flunitrazepam binding levels were approximately the same in both molecular and granule cell layers. With the exception of kainate binding sites, the distribution of binding sites was identical to that seen in the cerebellar cortex of mammals. Our results support the concept that the chemoarchitecture of the cerebellar cortex has been conserved in the course of vertebrate evolution.
Animals↗
Autoradiography of L-type and N-type calcium channels in aged rat hippocampus, entorhinal cortex, and neocortex.
The present study examined brains from 6, 17, and 32 month old male (F344x BN)F1 rats to determine whether there was any age-related change in the distribution or density of L-type and N-type Ca2+ channels in hippocampus, entorhinal cortex, and neocortex, areas commonly involved in the generation of epileptic seizures. The L-type channel antagonist PN200-110 and the N-type channel antagonist omega-conotoxin GVIA were used to determine specific binding densities and the autoradiographic distribution of ligand binding was quantified by computer-assisted densitometry. One-way ANOVA noted a significant variance in the mean value of binding density between different age groups only in neocortex laminae IV-VI for [(3)H]PN200-110 binding (P < 0.05). Post-hoc testing indicated that the mean value of the 17 month old group was significantly less than those of the 6 and 32 month old groups (P < 0.05). These results indicate no overall age-related change in the number of L-type and N-type Ca2+ channels in brain areas frequently involved in seizure activity and suggest that age-related changes in brain Ca2+ physiology may be associated with changes in voltage-gated Ca2+ channel function rather than channel number.
Age Factors↗
Excitatory amino acid, GABA(A), and GABA(B) binding sites in human striate cortex.
Receptor autoradiography was used to study the laminar distribution of excitatory amino acid, GABA(A), and GABA(B) binding sites in human striate cortex. Binding sites for all these receptor subtypes were found within striate cortex, but there were marked differences in the laminar distribution of binding sites. NMDA binding sites were most dense in layers 1-4C, with highest density in layer 4C and lower levels in layers 5 and 6. Among non-NMDA binding sites, alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid binding sites had highest levels in layers 1-3, intermediate levels in layers 5 and 6, and lowest levels in layers 4B and 4C. Kainate and metabotropic binding sites were more uniformly distributed across cortical laminae, with a trend toward highest kainate binding in layers 5 and 6. GABA(A)/benzodiazepine binding sites had highest levels in layers 2, 3, and 4C, with intermediate levels in 4B and lowest levels in layers 1, 5, and 6. GABA(B) binding sites were uniformly distributed across laminae. There was no evidence of a "columnar" or "blob" pattern of any binding site within any of the laminae. With the exception of kainate, metabotropic excitatory amino acid, and GABA(B) binding sites, the laminar distribution of binding sites within striate cortex was different than that seen in adjacent visual cortex.
Aged↗