Search PubMed⌕ Search

Biomedical subjects

J T Coyle

Publications and source records attributed to J T Coyle.

At least 343 records · Page 19Linked to original sources
PubMed1978

Microinjection of kainic acid into the rat hippocampus.

The effects of unilateral injection of kainic acid into the rate hippocampus have been examined in terms of morphologic, neurochemical and behavioral sequelae. Infusion of 10 nmoles if kainate causes a rapid and complete degeneration of neuronal perikarya in the entire hippocampal formation followed by gliosis and atrophy of the region. This unilateral neuronal loss is accompanied by a 50% decrease in the specific activity of the biochemical markers for GABAergic neurons including glutamic acid decarboxylase, endogenous GABA and synaptosomal uptake of [3H]GABA. The extrinsic hippocampal cholinergic and noradrenergic afferents also exhibit significant alteration. Although the specific activity of choline acetyltransferase is unaffected and the specific activity of tyrosine hydroxylase is significantly increased in the injected hippocampus, the synaptosomal high affinity uptake process for [3H]choline and [3H]norepinephrine are significantly reduced at 10 days after injection. Whereas the level of endogenous acetylcholine is elevated in the lesioned hippocampus at 2 days after injection, the level of endogenous norepinephrine is reduced. For several hours after intrahippocampal injections of 5 nmoles or more of kainate, rats exhibit epileptiform behavior. Intrahippocampal injection of kainate may be a useful rodent model for temporal lobe seizure disorders.

Animals↗
PubMed1978

In situ injection of kainic acid: a new method for selectively lesioning neural cell bodies while sparing axons of passage.

The morphologic sequelae following stereotaxic injection into the rat striatum of kainic acid, a conformationally restricted analogue of glutamate, were examined by means of bright field, histofluorescence and electron microscopic techniques. The neuropathologic response to kainate injection occurs in two distinct phases. First, the intrinsic neurons of the striatum undergo a rapid degeneration during the first 48 hours after injection; this is characterized by the sequential loss of cytoplasmic Nissl-substance (chromatolysis), shrinkage of the perikarya, clumping of the nuclear chromatin and finally disruption of the nuclear membrane. Between one and three weeks after injection, a marked proliferation of astrocytes in the gray matter formerly populated by neurons characterizes the second phase. The region of several neuronal loss in the kainate injected striatum is approximately spherical in shape, and its extent is non-linearly related to the amount of kainate injected. The neuropil of the injected striatum is markedly disrupted due to the death of intrinsic neurons and loss of their processes. Yet, histofluorescence microscopy demonstrates that the dopaminergic axons projecting from the substantia nigra do not degenerate in the kainate injected striatum; electron microscope studies indicate that corticofugal fibers traversing the striatum are also unaffected by kainate. Many presynaptic boutons, presumably of extrinsic origin, are intact up to ten days after injection; osmophilic vestiges of postsynaptic elements remain adherent to these boutons. Numerous phagocytic astrocytes are observed throughout the lesioned area. These morphologic studies provide (direct) evidence that in situ injection of kainic acid in brain causes a selective degeneration of neurons with cell bodies in the area of the injection but spares axons that arise from perikarya outside the region but pass through or terminate in the injected area. Thus, in situ injection of kainic acid is a new technique for making selective brain lesions that will be useful for examining neuronal connectivity.

Animals↗
PubMed1978

Absence of a relationship between sympathetic neuronal activity and turnover of serum dopamine-beta-hydroxylase.

The effects of pharmacological alteration of adrenergic transmission on the rate of entrance of dopamine-beta-hydroxylase (DBH) into the circulation were assessed in rats by an immunological method in which the kinetics of recovery of serum DBH activity were measured after depletion of the enzyme by treatment with anti-rat DBH antiserum. Neither alpha-receptor blockade with phenoxybenzamine nor ganglionic blockade with clorisondamine altered the rate by which DBH enters the bloodstream although both treatments markedly altered serum catecholamine levels. Prolonged treatment of newborn rats with guanethidine produced a severe peripheral sympathectomy but only a moderate decrease (30%) in serum DBH levels. In the sympathectomized rats, the rate of entrance of DBH into the circulation was significantly reduced whereas the half-life and rate of degradation of the enzyme was unchanged. These results indicate that the major portion of serum DBH does not enter the circulation by means of exocytotic release of the soluble enzyme.

Animals↗
PubMed1978

Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation.

Stereotaxic injection of kainic acid into the striatum of adult rats causes degeneration of neurons intrinsic to the striatum but spares axons of passage and of termination of extrinsic neurons. Neurochemical and histologic studies demonstrate that striatal neurons are almost insensitive to kainate at 7 days after birth and that their vulnerability increases with age; by 3 weeks after birth, striatal injection of kainate produces a lesion comparable to that of the adult. The intensity and duration of the acute behavioral response to kainate also increases with age. The maturational increase in striatal neuronal sensitivity to kainate correlates with the development of glutamatergic innervation to the striatum, as measured by [3H]glutamate uptake by synaptosomes, and with the development of a postsynaptic, high-affinity receptor site for kainate. These ontogenetic studies provide additional evidence that kainate's neurotoxicity is a receptor-mediated event related to glutamatergic innervation of vulnerable neurons.

Animals↗
PubMed1978

Visualization of central noradrenergic neurons in thick sections by the unlabeled antibody method: a transmitter-specific Golgi image.

The unlabeled peroxidase-antiperoxidase method has been used with an antiserum against rat dopamine-beta-hydroxylase (DBH) to obtain a three-dimensional image of noradrenergic cell bodies and their processes in thick Vibratome sections of rat brain. This method stains DBH-positive neurons exclusively with a result similar to that of the Golgi method, which makes it possible to analyze the geometric plan of these neurons and their projections in the central nervous system. In 100-micron sections, DBH-positive axons can be followed over long distances, and the results indicate that their distribution in cerebral and cerebellar cortex is not diffuse but has a strict geometric order.

Animals↗
PubMed1977

GABA receptor binding in rat striatum: localization and effects of denervation.

Intrastriatal injection of 2 microgram of kainic acid, a conformationally restricted analogue of glutamate, causes degeneration of GABAergic neurons intrinsic to the striatum while sparing axons of extrinsic neurons terminating in or passing through the region. From 2 to 15 days after striatal lesion with kainate, the sodium-independent binding of [3H]-psi-aminobutyric acid (GABA) to striatal membranes is increased 200% above that of control. Differences in the amount of endogenous GABA contaminating the membrane preparations do not account for the increased receptor binding. Scatchard analysis reveals an increased affinity of the GABA receptor in the kainate-lesioned striatum with no change in the number of binding sites. The subcellular distribution of the receptor as well as the sensitivity of the receptor to several agonists and antagonists is unchanged by the kainate lesion. Ablation of the nigrostriatal dopaminergic pathway by nigral injection of 8 microgram of 6-hydroxydopamine reduces by 22% the specific binding of [3H]GABA in the ipsilateral striatum and attenuates by 33% the increase in GABA receptor binding produced by the striatal kainate lesion. These studies demonstrate that (1) the sodium independent binding sites for GABA in striatum are localized on axons of extrinsic neurons, and (2) the affinity of these receptors for GABA increases in response to GABAergic denervation.

Aminobutyrates↗
PubMed1977

Selective destruction of neurons by a transmitter agonist.

Microinjection of nanomole amounts of kainic acid, a heterocyclic analog of glutamate, into the cerebellums of adult hamsters and rats causes rapid degeneration of Purkinje, basket, stellate, and Golgi II cells, neurons that receive synaptic input from granule cells, whereas the granule cells themselves are spared. This selectivity is consistent with the evidence that glutamate is the granule cell transmitter and supports the hypothesis that kainic acid exerts its neurotoxic effects through glutamate receptors.

Animals↗
PubMed1977

Striatal lesions with kainic acid: neurochemical characteristics.

Stereotaxic injection of 2.5 microng of kainic acid, a rigid analogue of glutamate into the rat striatum caused a 70% reduction in the striatum of the cholinergic parameters, choline acetyltransferase, acetylcholine and synaptosomal uptake of choline and a similar reduction in the GABAergic parameters, glutamic acid decarboxylase, psi-aminobutyric acid (GABA) and synaptosomal uptake of GABA. In contrast, the striatal content of dopamine and the synaptosomal uptake of dopamine were unchanged, and the activity of tyrosine hydroxylase was significantly increased. Significant changes in the activity of neurotransmitter synthesizing enzymes were demonstrable within 6h after injection of 2.5 microng of kainic acid and maximal effects occurred at 48h; the activities of choline acetyltransferase and glutamic acid decarboxylase remained depressed up to 21 days after injection. The kinetic characteristics of striatal tyrosine hydroxylase were altered 48h after injection with a two-fold increase in the Vmax for tyrosine and a three-fold reduction in Km for the pteridine cofactor. In contrast to the effects of kainic acid, the injection of copper sulfate, a non-specific toxin, caused a proportionate reduction in the dopaminergic as well as the cholinergic and GABAergic presynaptic markers. The kainate lesion caused an 85% decrement in the activity of dopamine-sensitive adenylate cyclase, a 40% reduction in the specific binding of [3H]quinuclidinyl benzilate and a 195% increase in the specific binding of [3H]GABA in the striatum. The morphology of the kainate injected striatum was markedly altered with nearly a complete loss of intrinsic neurons, increased number of glial cells but intact internal capsule fibers. Intracerebral injection of nanomolar quantities of kainic acid appears to cause degeneration of neurons with cell bodies near the injection site while sparing axons terminating in or passing through the region.

Adenylyl Cyclases↗
PubMed1977

Major innervation of newborn rat cortex by monoaminergic neurons.

A major monoaminergic innervation in infant rat neocortex, predominantly in layer IV, has been demonstrated by ultrastructural and biochemical studies after the administration of exogenous catecholamine precursors and congeners. One-third of all cortical synapses have an uptake-storage mechanism for catecholamines. In newborn cortex, the storage capacity for catecholamines is tenfold greater than the endogenous levels, and the uptake-storage mechanism matures earlier than the ability to synthesize neurotransmitter.

Adrenergic Fibers↗