Autoradiographic characterization of N-methyl-D-aspartate-, quisqualate- and kainate-sensitive glutamate binding sites.

Quantitative autoradiography was used to characterize the pharmacological specificity and anatomical distributions of subtypes of L-[3H]glutamate binding sites in rat brain. One population of sites was sensitive to N-methyl-D-aspartate (NMDA) and other compounds thought to be specific for the NMDA receptor. This site was enriched in stratum radiatum of hippocampus (CA1) where it constituted about 80% of glutamate binding sites and it represented a variable portion of glutamate binding sites throughout the brain.

Alterations in L-glutamate binding in Alzheimer's and Huntington's diseases.

Brain sections from patients who had died with senile dementia of the Alzheimer's type (SDAT), Huntington's disease (HD), or no neurologic disease were studied by autoradiography to measure sodium-independent L-[3H]glutamate binding. In brain sections from SDAT patients, glutamate binding was normal in the caudate, putamen, and claustrum but was lower than normal in the cortex. The decreased cortical binding represented a reduction in numbers of binding sites, not a change in binding affinity, and appeared to be the result of a specific decrease in numbers of the low-affinity quisqualate binding site.

Evidence for the presynaptic localization of opiate binding sites on striatal efferent fibers.

Using quantitative receptor autoradiography, [3H]D-Ala-D-Leu-enkephalin (DADL) and [3H]naloxone binding were studied in rat striatum and striatal projection areas (globus pallidus (GP) and substantia nigra pars reticulata (SNr] after unilateral striatal kainic acid lesions. [3H]DADL and [3H]naloxone binding were each examined by two methods. Initially, [3H]DADL binding was performed in 50 mM Tris-HCl (pH 7.

Characterization of benzodiazepine receptor changes in substantia nigra, globus pallidus and entopeduncular nucleus after striatal lesions.

This study explored the character and time course of benzodiazepine (BDZ) receptor changes in substantia nigra pars reticulata, globus pallidus and entopeduncular nucleus after striatal kainate lesions in the rat. Receptor levels at the lesion site and striatal projection areas were measured at 1 week, 1 month and 2 to 3 months after the lesion. One week after the lesion, no receptor changes in substantia nigra pars reticulata, globus pallidus, or entopeduncular nucleus were detected.

Benzodiazepine and GABA receptors in early Huntington's disease.

We compared autoradiographic measurements of GABA and benzodiazepine receptors in the brains of two early cases of Huntington's disease (HD), five controls, and four advanced cases of HD. These receptors increase in lateral globus pallidus and decrease in putamen early in the disease, before there is any extensive cell loss and atrophy. The cause of these receptor changes is unknown, but could imply dysfunction rather than death of striatal neurons.

Neurochemical anatomy of movement disorders.

Recent advances in our understanding of the neurochemical anatomy of the pyramidal and extrapyramidal motor systems have led to more logical and effective pharmacotherapies for movement disorders. Our knowledge of the neurochemistry of Parkinson's and Huntington's diseases is the most complete. In the future, the same approaches used in these diseases need to be used on the somewhat less common disorders such as progressive supranuclear palsy, dystonia, Tourette's syndrome, and cerebellar ataxias.

Quantitative autoradiographic distribution of L-[3H]glutamate-binding sites in rat central nervous system.

Quantitative autoradiography was used to determine the distribution of L-[3H]glutamate-binding sites in the rat central nervous system. Autoradiography was carried out in the presence of Cl- and Ca2+ ions. Scatchard plots and Hill coefficients of glutamate binding suggested that glutamate was interacting with a single population of sites having a K-D of about 300 nM and a capacity of 14.

GABA and benzodiazepine receptors in basal ganglia function.

GABA and its associated benzodiazepine interactions play an important role in basal ganglia function. Distinctive GABA, benzodiazepine and opiate receptor changes occur in response to striatal lesions and in the human neurodegenerative disorder, Huntington's disease (HD). In animal experiments, the in vivo administration of [3H]flunitrazepam labels benzodiazepine receptors and can demonstrate the receptor changes seen after striatal lesions.

Computer-assisted estimates of lesion sizes and shrinkage in denervated areas from receptor autoradiograms using a digitizing tablet.

Area measurements taken from receptor autoradiograms were employed to estimate the size of striatal kainate lesions and the amount of shrinkage in deafferented projection areas. There was no significant difference in the size of substantia nigra (SN) on the denervated side as compared to the intact side one week and one month after unilateral striatal lesions. Although there was no change in the size of globus pallidus (GP) on the lesioned side one week after the lesion, there was a 17% shrinkage one month after the lesion.

Glutamate or aspartate as a possible neurotransmitter of cerebral corticofugal fibers in the monkey.

We measured high affinity glutamate uptake in subcortical projection sites of monkey (Macaca fascicularis) 8 weeks after unilateral ablation of Brodmann's areas 4 and 6. Uptake decreased ipsilateral to the lesion in ventrolateral nucleus of thalamus, caudate nucleus, and pons. Uptake also decreased contralateral to the lesion in cervical and lumbar spinal cord.

Quantitative autoradiography of L-[3H]glutamate binding to rat brain.

A technique has been developed to investigate sodium-independent L-[3H]glutamate binding in rat brain sections using quantitative autoradiography and tritium-sensitive film. Binding is rapid (reaching equilibrium in 5 min) and reversible (having a t 1/2 of dissociation of 0.38 min).

Changes in [3H]muscimol binding in substantia nigra, entopeduncular nucleus, globus pallidus, and thalamus after striatal lesions as demonstrated by quantitative receptor autoradiography.

A quantitative autoradiographic technique for measuring the binding of [3H]muscimol to central nervous system GABA receptors is described using tritium-sensitive film. [3H]Muscimol binding was studied in primary and secondary striatal projection areas of rat brain following kainic acid lesions of the striatum. Seven days after the lesion, binding affinities in the striatum and its projection areas were not altered significantly.

Quantitative autoradiography of neurotransmitter receptors in Huntington disease.

We studied gamma-aminobutyric acid (GABA), benzodiazepine, and muscarinic cholinergic receptor-binding by quantitative autoradiography. In coronal sections from the brain of a patient with Huntington disease, binding for all three receptors in caudate and putamen was lower than control values. Binding to GABA and benzodiazepine receptors was increased in lateral and medial pallidum and decreased in ventrolateral thalamus.

Quantitative autoradiography of [3H]muscimol binding in rat brain.

A simple quantitative autoradiographic technique for the study of neurotransmitter receptors that includes the use of a tritium-sensitive film permits saturation, kinetic, and competition studies of brain samples as small as 0.01 cubic millimeter. This technique was used to study [3H]muscimol binding in rat brain.

Primary culture of capillary endothelium from rat brain.

To provide an in vitro system for studies of brain capillary function we developed a method for culture of brain capillary endothelial cells. Capillaries were isolated from rat brain and enzymatically treated to remove the basement membrane and contaminating pericytes. Subsequent Percoll gradient centrifugation resulted in a homogeneous population of capillary endothelial cells that attached to a collagen substrate and incorporated [3H]thymidine.

Decreased glutamate uptake in subcortical areas deafferented by sensorimotor cortical ablation in the cat.

Evidence that L-glutamate is a neurotransmitter of corticofugal fibers was sought by measuring changes in several biochemical markers of neurotransmitter function after pericruciate (sensorimotor) ablations in cats. Two weeks after cortical ablation, samples from various brain regions were analyzed for high affinity uptake of glutamate, gama-aminobutyric acid (GABA), glycine, alanine, and tyrosine. Amino acid levels and the activity of choline acetyltransferase (CAT) also were determined.

GABA as the pallidothalamic neurotransmitter: implications for basal ganglia function.

GABA levels, high affinity GABA uptake and glutamic acid decarboxylase levels are reduced in rat ventroanterolateral thalamic nucleus after destruction of the entopeduncular nucleus with kainic acid. This is strong evidence that GABA is an entopedunculothalamic neurotransmitter. The striatoentopeduncular pathway is also GABAergic.