Search PubMed⌕ Search

Biomedical subjects

R L Albin

Publications and source records attributed to R L Albin.

At least 91 records · Page 5Linked to original sources
PubMed1992

Zinc modulates GABAB binding in rat brain.

The effects of ZnCl2 on [3H]GABA binding to GABAA and GABAA binding sites were investigated using receptor autoradiography. At concentrations exceeding 100 microM, zinc non-competitively inhibited GABAB binding in a dose dependent fashion. GABAA binding was not inhibited significantly by zinc eliminating the possibility of a non-specific effect of zinc. Increased calcium concentrations up to 10 mM enhanced total GABAB binding but did not prevent zinc induced inhibition of GABAB binding, indicating a separate site of action for these cations at the GABAB binding site. In some regions, zinc modulates GABAB binding in a biphasic manner as concentrations of 10-100 microM zinc significantly enhanced GABAB binding in the hippocampus and the molecular layer of the cerebellum but not in the thalamus. These results provide further evidence for a neuromodulatory role for zinc in the central nervous system.

Animals↗
PubMed1992

GABAA, GABAB, and benzodiazepine binding sites in the cerebellar cortex of the red-eared turtle (Pseudemys scripta).

We used receptor autoradiography to ascertain the distribution of GABAA and GABAB binding sites in the cerebellar cortex of the red-eared turtle (Pseudemys scripta). GABAA binding sites were found in both molecular and granule cell layers with highest levels in the granule cell layer. GABAB binding sites were found at highest level in the molecular layer. Benzodiazepine binding sites were found in approximately equal abundance in both layers. Little binding of any ligand was seen in the Purkinje cell layer. Our results are similar to those found in mammals and other non-mammalian vertebrates and indicate that the organization of inhibitory pathways of the cerebellar cortex has been conserved in the course of vertebrate evolution.

Animals↗
PubMed1992

Localization of striatal excitatory amino acid binding site subtypes to striatonigral projection neurons.

Quantitative autoradiography was used to examine the cellular localization of excitatory amino acid binding sites in the striatum following selective lesion of striatonigral projection neurons. Degeneration of striatonigral neurons was induced unilaterally by injection of the suicide transport toxin, volkensin, into the left substantia nigra. Twelve days following nigral volkensin injection there was a reduction of all excitatory amino acid binding site subtypes in the striatum ipsilateral to the injected nigra. The reduction in N-methyl-D-aspartate (NMDA) binding sites was significantly greater than the loss of D,L-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), kainate and metabotropic binding. These results indicate that there are NMDA, AMPA, metabotropic and kainate binding sites on striatonigral projection neurons and suggest that the NMDA subtype may be selectively enriched on striatonigral neurons.

Animals↗
PubMed1992

Preferential loss of striato-external pallidal projection neurons in presymptomatic Huntington's disease.

We have reported previously that striatal projection neurons are differentially affected in the course of Huntington's disease, and in a prior patient report we noted that differential loss of striatal projection neurons occurs also in patients with presymptomatic Huntington's disease. Striatal neurons projecting to the external segment of the globus pallidus or the substantia nigra show evident loss, whereas those projecting to the internal segment of the globus pallidus appear relatively spared at presymptomatic and early stages of symptomatic Huntington's disease. We now report similar findings in a second apparently presymptomatic Huntington's disease allele carrier.

Adult↗
PubMed1992

Excitatory amino acid binding sites in the basal ganglia of the rat: a quantitative autoradiographic study.

Quantitative receptor autoradiography was used to determine the distribution of excitatory amino acid binding sites in the basal ganglia of rat brain. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, N-methyl-D-aspartate, kainate, quisqualate-sensitive metabotropic and non-N-methyl-D-aspartate, non-kainate, non-quisqualate glutamate binding sites had their highest density in striatum, nucleus accumbens, and olfactory tubercle. Kainate binding was higher in the lateral striatum but there was no medial-lateral striatal gradient for other binding sites. N-Methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding sites were most dense in the nucleus accumbens and olfactory tubercle. There was no dorsal-ventral gradient within the striatal complex for the other binding sites. Other regions of the basal ganglia had lower densities of ligand binding. To compare binding site density within non-striatal regions, binding for each ligand was normalized to the striatal binding density. When compared to the striatal complex, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and metabotropic binding sites had higher relative density in the globus pallidus, ventral pallidum, and subthalamic nucleus than other binding sites. Metabotropic binding also had a high relative density in the substantia nigra. Non-N-methyl-D-aspartate, non-kainate, non-quisqualate glutamate binding sites had a high relative density in globus pallidus, ventral pallidum, and substantia nigra. N-Methyl-D-aspartate binding sites had a low relative density in pallidum, subthalamic nucleus, substantia nigra and ventral tegmental area. Our data indicate heterogeneous distribution of excitatory amino acid binding sites within rat basal ganglia and suggest that the character of excitatory amino acid-mediated neurotransmission within the basal ganglia is also heterogeneous.

Animals↗
PubMed1992

6-Hydroxydopamine lesions of the nigrostriatal pathway alter the expression of glutamate decarboxylase messenger RNA in rat globus pallidus projection neurons.

In situ hybridization was used to study the effect of 6-hydroxydopamine-induced damage to the midbrain dopaminergic neurons on the level of glutamate decarboxylase mRNA in globus pallidus neurons in the rat. Some animals received an injection of Fluoro-gold in the entopeduncular nucleus or the substantia nigra prior to the 6-hydroxydopamine lesion in order to identify glutamic acid decarboxylase mRNA levels in pallidal neurons that project to one of these targets. Analysis was carried out on a sample of all pallidal neurons as well as neurons that were identified as projection neurons in control and lesioned groups. The loss of the dopamine-containing neurons in the substantia nigra resulted in significant increases in the percentage of globus pallidus neurons that expressed glutamate decarboxylase mRNA and in the amount of glutamate decarboxylase mRNA per globus pallidus neuron. These increases were noted in a sample of all pallidal neurons, as well as pallidal neurons that were identified as projecting to either the entopeduncular nucleus or the substantia nigra. In control animals, glutamate decarboxylase mRNA was clearly identified in globus pallidus neurons projecting to the entopeduncular nucleus, indicating that this recently reported projection is at least partially GABAergic. The results of this study indicate that substantia nigra dopaminergic neurons regulate globus pallidus neurons in the rat, and that removal of the dopaminergic input to the corpus striatum results in a significant increase in the amount of glutamate decarboxylase mRNA in pallidal neurons. The decreased firing rate of pallidal neurons that is seen following the loss of dopamine input appears to be accompanied by an increase in the level of glutamate decarboxylase mRNA in these neurons.

Animals↗
PubMed1992

A new, simple myelin stain.

A new and convenient myelin stain is described. Paraformaldehyde fixed tissue is serially immersed in a nitroblue tetrazolium solution and then in a diaminobenzidine solution. The result is distinct blue staining of myelinated fiber tracts. This technique has advantages over presently used myelin stains.

Animals↗
PubMed1992

Alternative excitotoxic hypotheses.

The concept of excitotoxicity, neuronal death produced by overstimulation of excitatory amino acid receptors, has become a popular way of explaining the pathogenesis of neuronal death in a variety of acute and chronic neurologic diseases. While there is strong evidence supporting the role of excitotoxicity in acute processes such as hypoxia/ischemia and hypoglycemia, the role of excitotoxicity in chronic neurologic disease is not firmly established. To account for the inter- and intraregional variations in pathology of different neurodegenerative disorders, we suggest two modified forms of the excitotoxic hypothesis in which specific populations of neurons become more vulnerable to excitotoxic insult either by (1) possessing abnormal excitatory amino acid receptor subtypes or (2) being afflicted by any disease process that impairs cellular energy metabolism or otherwise decreases neuronal membrane potential. In these ways, excitotoxicity may be a final common pathway of neuronal death in a variety of neurodegenerative diseases.

Acute Disease↗
PubMed1991

Excitatory and inhibitory amino acid binding sites in human dentate nucleus.

Autoradiography of excitatory and inhibitory amino acid binding sites in human dentate nuclei indicated virtually no binding to N-methyl-D-aspartate (NMDA) or gamma-aminobutyric acidB (GABAB) binding sites, and a low density of kainate binding sites. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, metabotropic-quisqualate, benzodiazepine, and gamma-aminobutyric acidA (GABAA) binding sites were present in moderate abundance. Our NMDA results differ from those found previously in rodents. GABAA receptors are probably the primary mediators of inhibitory neurotransmission and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and metabotropic-quisqualate receptors are probably the primary mediators of excitatory neurotransmission within the human deep cerebellar nuclei.

Adult↗
PubMed1991

Preproenkephalin messenger RNA-containing neurons in striatum of patients with symptomatic and presymptomatic Huntington's disease: an in situ hybridization study.

Previous studies have revealed a loss of enkephalin immunoreactivity in the terminals of striatal neurons projecting to the external globus pallidus in patients with early grades of Huntington's disease (HD). To assess the status of the perikarya of striatal enkephalinergic neurons, we performed in situ hybridization histochemistry with a radiolabeled RNA probe complementary to preproenkephalin messenger RNA. We studied postmortem brain tissue of 6 patients with symptomatic HD, 7 control subjects, and 2 presymptomatic carriers of the HD allele. There was a significant reduction in the areal density of striatal neurons expressing preproenkephalin messenger RNA in the patients with symptomatic HD, but the level of labeling in the remaining cells was not altered compared with the control subjects. In the specimens from presymptomatic individuals, there was no reduction of areal density of preproenkephalin messenger RNA-containing neurons in the striatum, despite the fact that loss of enkephalin immunoreactivity in the external globus pallidus had been previously demonstrated in the same brains. The results correlate with the previous demonstration of depleted enkephalin immunoreactive terminals in the external globus pallidus in patients with symptomatic HD. They also suggest that the early loss of enkephalin immunoreactivity observed in the external globus pallidus of presymptomatic carriers of the HD allele is not related to a generalized death of striatal enkephalinergic neurons early in the course of the disease.

Adolescent↗
PubMed1991

A novel device for chronic intracranial drug delivery via microdialysis.

A system is described for chronic intracranial drug administration in the rat using a modified in vivo microdialysis probe coupled to an Alzet model 2002 osmotic minipump. The results presented demonstrate that this system can be used for the chronic administration of quinolinic acid with minimal non-specific damage. Each pump delivered approximately 225 microliters of solution over a period of 19-20 days when tested in vitro. The dialysis units were uniform in function, delivering greater than 93% of the [3H]quinolinic acid initially loaded into the minipump. For in vivo analysis of this apparatus the dose of quinolinic acid tested produced extensive destruction of the striatum. The present system allows reliable drug diffusion over a relatively large area without pressure injection variability. In conclusion, we have developed a simple and inexpensive technique for administration of drugs into brain parenchyma with substantial advantages over previously used techniques.

Animals↗
PubMed1990

Excitatory amino acid binding sites in the periaqueductal gray of the rat.

We used receptor autoradiography to determine the distribution of excitatory amino acid (EAA) binding site subtypes in the periaqueductal gray (PAG) of the rat. N-Methyl-D-aspartate (NMDA), kainate, quisqualate-ionotropic, and quisqualate-metabotropic binding sites were all present in the PAG. Distribution was inhomogeneous with greatest density of all binding site subtypes in the dorsolateral subdivision and lowest density in the ventrolateral subdivision. Relative to regions of brain with high densities of EAA binding site subtypes, quisqualate-metabotropic binding sites had the highest relative density and NMDA binding sites the least. The presence of all subtypes of EAA binding sites in the PAG suggests that EAA action within the PAG is likely to be complex.

Amino Acids↗
PubMed1990

Two types of quisqualate receptors are decreased in human olivopontocerebellar atrophy cerebellar cortex.

We used receptor autoradiography to study the distribution of ionotropic and metabotropic quisqualate (QA) receptors in normal human cerebellar cortex and cerebellar cortex from 7 cases of olivopontocerebellar atrophy (OPCA). In normal human cerebellar cortex, both types of QA receptors were densest in the molecular layer. Both ionotropic and metabotropic QA receptors were significantly diminished in the molecular layer of OPCA specimens. These results suggest that both ionotropic and metabotropic QA receptors are localized on Purkinje cell dendrites.

Autoradiography↗
PubMed1990

Autoradiographic localization of inhibitory and excitatory amino acid neurotransmitter receptors in human normal and olivopontocerebellar atrophy cerebellar cortex.

We used standard techniques of receptor autoradiography to study the distribution of inhibitory and excitatory amino acid neurotransmitter receptors in human normal cerebellar cortex. Benzodiazepine (BDZ) receptor density was relatively high in both granule cell and molecular layers. GABAA receptor density was highest in granule cell layer with lower receptor density in molecular layer. There was a lower density of GABAB receptors than GABAA receptors in both molecular and granule cell layers with a relatively higher density of GABAB receptors in molecular layer than in granule cell layer. In granule cell layer, the density of the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors was greatest whereas in molecular layer the quisqualate (QA) receptor subtype density was greatest. With [3H]N-(1-[2-thienyl]cyclohexyl)3-4-piperidine as a ligand, there was no specific binding to the phencyclidine receptor. Molecular layer was also characterized by relatively high density of a non-NMDA/non-QA displaceable glutamate binding site. We studied also the cerebellar cortex of 4 cases of olivopontocerebellar atrophy (OPCA), a syndrome in which Purkinje and granule cells degenerate. In these specimens, there was significant decrement of BDZ and GABAA receptors in both molecular and granule cell layers, with loss of GABAB receptors in molecular layer. NMDA receptors were depleted in granule cell layer while QA receptors and the non-NMDA/non-QA glutamate binding site were significantly depleted in molecular layer. Our normal human and OPCA data are largely consistent with animal data about the cellular localization of cerebellar cortical amino acid neurotransmitter receptors.

Autoradiography↗
PubMed1990

The death of Nicholas Bolkonski. Neurology in Tolstoy's War and Peace.

Painstaking realism is an essential feature of the fiction of Count Leo Tolstoy. One example of Tolstoy's attention to detail is the description of the death of Prince Nicholas Bolkonski in War and Peace. The information provided in War and Peace allows the identification of the prince's terminal illness as a brain-stem stroke and is probably the first description of the one-and-a-half syndrome. Prince Bolkonski is also portrayed as suffering from a dementing process. Tolstoy used the character of Prince Bolkonski to exemplify the rationalistic, Western-influenced aristocracy that dominated Russia at the end of the 18th century. Prince Bolkonski's decline and apoplectic death parallel the fate of Enlightenment thought in Eastern Europe. The clinical detail employed in this case illustrates how Tolstoy used symbolic characters without sacrificing the realism of War and Peace.

Cerebrovascular Disorders↗
PubMed1990

Striatal and nigral neuron subpopulations in rigid Huntington's disease: implications for the functional anatomy of chorea and rigidity-akinesia.

Neuropeptide immunohistochemistry was used to test several hypotheses of the anatomical bases of chorea and rigidity-akinesia. To test the hypothesis that elevated concentration of striatal somatostatin causes chorea, we visually compared the density of striatal neurons containing somatostatin and neuropeptide Y in brains affected by choreic or rigid-akinetic Huntington's disease (HD). The density of these neurons was elevated in both rigid-akinetic and choreic HD specimens with an apparently normal total number of these neurons, indicating that elevated somatostatin concentration, by itself, does not lead to chorea. We tested the hypothesis that rigid-akinetic HD results from deficient dopaminergic nigrostriatal neurotransmission by examining tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra. In rigid-akinetic HD brains, there was no obvious reduction of nigral TH-IR neurons, indicating that rigid-akinetic HD is probably not due to loss of nigral dopaminergic neurons. Finally, we also examined the status of striatal projection neurons and found near total loss of all striatal neurons projecting to the lateral globus pallidus, medial globus pallidus, and substantia nigra in brains affected by rigid-akinetic HD in contrast to the preservation of neurons projecting to the medial globus pallidus in choreic HD. These results are consistent with the hypothesis that chorea results from preferential loss of striatal neurons projecting to the lateral globus pallidus and that rigid-akinetic HD is a consequence of the additional loss of striatal neurons projecting to the medial segment of the pallidum.

Adult↗
PubMed1990

Distribution and kinetics of GABAB binding sites in rat central nervous system: a quantitative autoradiographic study.

[3H]GABA quantitative autoradiography was used to examine the binding kinetics and regional distribution of GABAB receptors in rat brain. The regional distribution was compared to that of GABAA receptors. At 4 degrees C, [3H]GABA binding to GABAB receptors reached equilibrium within 45 min. The association and dissociation rate constants for GABAB binding to outer neocortical layers were 2.87 +/- 0.17 X 10(5) min-1 M-1 and 0.0966 +/- 0.0118 min-1, respectively, indicating a dissociation constant of 336 +/- 40 nM. Saturation binding studies in the same region yielded a dissociation constant for GABAB receptors of 341 +/- 41 nM while that of GABAA receptors was 92 +/- 10 nM. While the affinities of each type of GABA receptor were uniform across brain regions, the maximal number of binding sites for both types of GABA receptor varied across regions. The distributions of the two receptors in rat brain were different in the olfactory bulb, cerebellum, thalamus, neocortex, medial habenula and interpeduncular nucleus. Areas high in GABAB binding included the medial and lateral geniculates, the superior colliculus and certain amygdaloid nuclei. Binding to white matter tracts and ventricles was negligible. The distribution of GABAB receptors was in agreement with previously postulated sites of action of baclofen.

Animals↗