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Biomedical subjects

J T Coyle

Publications and source records attributed to J T Coyle.

At least 271 records · Page 15Linked to original sources
PubMed1982

Glutamate stimulation of 45Ca uptake by rat striatal synaptosomes.

The effects of acidic excitatory amino acids and 60 mM K+ on 45Ca uptake by synaptosomes prepared from rat striatum were examined. Both glutamic acid and 60 mM K+ significantly stimulated the uptake of 45Ca and these effects were antagonized by 30 mM Mg2+ and 0.5 mM La3+ but not by 5 microM tetrodotoxin. Neither kainic acid nor N-methyl-D,L-aspartic acid significantly affected the uptake of 45Ca. The results suggest that glutamate may activate a presynaptic receptor that is directly linked to calcium channels.

Animals↗
PubMed1982

Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain.

Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer's disease and senile dementia of the Alzheimer's type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (greater than 75 percent) and selective degeneration in these patients and provide a pathological substrate of the cholinergic deficiency in their brains. Demonstration of selective degeneration of such neurons represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and, as such, points to a critical subcortical lesion in Alzheimer's patients.

Acetylcholine↗
PubMed1982

Neurotransmitter chemistry in feline GM1 gangliosidosis: a model for human ganglioside storage disease.

Assays for synaptosomal high-affinity uptake activity (glutamate, gamma-aminobutyric acid, norepinephrine), neurotransmitter synthesizing enzymes (choline acetyltransferase, glutamate decarboxylase, tyrosine hydroxylase), and endogenous neurotransmitters were performed in cats with advanced inherited GM1 gangliosidosis. A significant reduction in uptake activity, ranging from 24 to 77% of control, was demonstrated in motor, occipital, and cerebellar brain regions. This reduction was unassociated with comparable alterations in neurotransmitter levels or synthesizing enzyme activity. We hypothesize that the defect of neurotransmitter inactivation is part of an overall abnormality of synaptic membrane function that could contribute to the neurological symptoms seen in the hereditary gangliosidoses.

Animals↗
PubMed1982

Dopaminergic dsyfunction in Tourette syndrome.

A prospective clinical and biochemical study on the effects of treatment with haloperidol has been performed in seven patients with Tourette syndrome. Pretreatment cerebrospinal fluid levels of homovanillic acid (CSF HVA) were significantly reduce in all patients, whereas 5-hydroxyindoleacetic acid was reduced in only two. With haloperidol treatment, symptoms decreased in all cases (21 to 88%) and clinical improvement was associated with an increased level of CSF HVA, often returning to the normal range. Optimal therapeutic response was found with serum levels of haloperidol between 1 and 4 ng/ml; however, disturbing side effects also occurred within this range. These results support the hypothesis that Tourette syndrome may result from a supersensitivity of dopaminergic receptors.

Adolescent↗
PubMed1982

Excitatory amino acid analogues: neurotoxicity and seizures.

The neurotoxic and convulsant properties of conformationally restricted and synthetic analogues of excitatory acidic amino acids were examined after stereotaxic injection into the striatum and the dentate gyrus of the hippocampal formation. In the striatum, neurotoxicity was quantified by the reduction in the activity of choline acetyltransferase and glutamate decarboxylase, markers for striatal intrinsic neurons. The following sequence of neurotoxic potencies was defined; kainic acid approximately equal to domoic acid much greater than alpha-keto kainic acid approximately equal to alpha-allo kainic acid greater than ibotenic acid approximately equal to cis-cyclopentyl glutamic acid greater than quisqualic acid approximately equal to N-methyl-D-aspartic acid. When normalized for neurotoxic potencies, a wide variation in the convulsant effects of the agents was observed after hippocampal injection. N-Methyl-D-aspartate produced nearly continuous electroencephalographic seizures for 2 hr after injection, where alpha-keto-kainate and kainate and quisqualate caused seizure activity for 64 and 45% respectively of this period; kainate, alpha-allo kainate and domoate caused intermittent seizure activity during approximately 30% of the recording period; ibotenate and cyclopentylglutamate had minimal convulsant effects. Seizures were associated with a significant reduction in the levels of norepinephrine and with increases in the levels of 5-hydroxyindoleacetic acid in the cortex and hippocampal formation and increases in the levels of gamma-aminobutyric acid in the hippocampal formation. Kainate, domoate, keto-kainate and alpha-allo-kainate caused extensive lesions of the hippocampal formation that also involved the pyriform cortex; ibotenate and cyclopentylglutamate caused uniform but substantial lesions limited to the dentate gyrus, whereas quisqualate and N-methyl-D-aspartate produced small and restricted lesions. The results demonstrate a poor correlation between the neurotoxic and convulsant potencies of these excitatory amino acid analogues and suggest that receptor-specific interactions may account for these disparities.

Amino Acids↗
PubMed1982

Neurotransmitter chemistry of lissencephalic cortex induced in ferrets by fetal treatment with methylazoxymethanol acetate.

Treatment of pregnant ferrets with 15 mg/kg of methylazoxymethanol acetate (MAM) at 33 days of fetal gestation results in offspring with cortical hypoplasia and lissencephally. Neurochemical analysis of 5 areas of cortex from 8-week-old offspring of MAM- or vehicle-treated jills indicated an overall enrichment in markers for catecholaminergic (tyrosine hydroxylase, norepinephrine) and cholinergic (choline acetyltransferase, acetylcholine) terminals but minimal change in the concentration of GABAergic markers (glutamate decarboxylase, gamma-aminobutyric acid); however, there did not appear to be a direct, inverse relationship between the concentration of catecholaminergic and cholinergic markers and the degree of hypoplasia in cortical subareas unlike what has been found previously in the rat.

Animals↗
PubMed1982

Fetally-induced noradrenergic hyperinnervation of cerebral cortex results in persistent down-regulation of beta-receptors.

Methylazoxymethanol acetate (MAM)-induced cortical hypoplasia resulted in a 2-fold increase in the concentration of norepinephrine and its metabolite, 3-methoxyl-4-hydroxyphenylglycol sulfate, and a 26% decrease in the Bmax for the beta-receptor ligand, [3H]dihydroalprenolol (DHA) in the rat cortex. Chronic treatment with desmethylimipramine did not further decrease DHA-labeled sites although prior lesion of the noradrenergic terminals with 6-hydroxydopamine markedly increased the number in the MAM-lesioned cortex.

Animals↗
PubMed1982

Neuroleptic drug level monitoring in psychiatry: focus on radioreceptor assay techniques.

Preliminary studies with the radioreceptor assay for neuroleptics suggest several advantages of this technique. Consistent with results obtained with other techniques, it is obvious that there is variation among individuals in terms of the serum levels obtained on given oral doses of neuroleptics; in addition, total daily dose correlates poorly with serum levels. The radioreceptor assay technique, however, is relatively uncomplicated and inexpensive and relies on methods that are commonly used in general hospital laboratories. Unlike gas chromatography/mass spectrometry, gas-liquid chromatography, and even radioimmunoassay--which are highly discriminative--the radioreceptor assay detects both parent drugs and active metabolites of virtually all classes of neuroleptics on the basis of their presumed physiologic mechanism of action.

Antipsychotic Agents↗
PubMed1982

Effects of kainic acid on high-energy metabolites in the mouse striatum.

Intrastriatal injection of either kainic acid (0.35 micrograms) or ibotenic acid (7.0 micrograms) in the mouse causes a profound and selective degeneration of striatal neurons accompanied by a secondary astrocytic response. The kainate injection (0.35 micrograms) resulted in significant decrements in the striatal levels of phosphocreatine and ATP by 30 min. a progressive reduction in adenosine phosphates between 30 min and 48 h, and a decrease in energy charge; whereas lactate levels increased by 44% at 2 h, glucose levels fell by 56%. Two hours after intrastriatal injection of ibotenic acid (7.0 micrograms) similar alternations in striatal high-energy phosphates and glucose disposition were found. Prior decortication protected against the neurotoxic effects of kainate in the mouse striatum and prevented the alterations in high-energy phosphates at 2 h although lactate levels increased by 212%. These findings in vivo are consistent with the hypothesis that the neurotoxic effects of acidic excitatory amino acids involve a profound activation of energy consumption by affected neurons.

Adenine Nucleotides↗
PubMed1982

Serum levels of anticholinergic drugs and impaired recent memory in chronic schizophrenic patients.

The authors tested working or recent memory in 24 stabilized schizophrenic outpatients who were taking psychotropic medication. Memory performance did not correlate with severity of schizophrenic symptoms, verbal IQ, or serum neuroleptic levels, but there was a significant inverse correlation between serum anticholinergic levels and performance on the memory task. The results suggest that therapeutic doses of anticholinergics may cause subtle impairments of cognitive functions.

Adult↗
PubMed1982

Clinical symptomatology, CSF neurotransmitter metabolites, and serum haloperidol levels in Tourette syndrome.

Our studies have demonstrated that TS patients show a high degree of sensitivity to butyrophenone blockade of dopaminergic receptors. The clinical response to extremely low serum levels of haloperidol includes sedating side effects, as well as therapeutic effects. These clinical changes are associated with significant increases in CSF HVA levels, which were abnormally decreased before treatment. CSF HIAA levels tended to be normal and did not change with haloperidol treatment. These results lend additional support to the hypothesis that TS is related to supersensitivity of dopaminergic receptors.

Adolescent↗