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J T Coyle

Publications and source records attributed to J T Coyle.

At least 181 records · Page 10Linked to original sources
PubMed1987

Quisqualate-sensitive, chloride-dependent transport of glutamate into rat brain synaptosomes.

A chloride-dependent transport process for glutamate has been identified in partially purified rat brain synaptosomes. This process shares many characteristics with the chloride-dependent sequestration process for glutamate in brain sonicates, which was previously thought to represent a quisqualate receptor, such as sensitivity to specific inhibitors and regulation by anions. Increasing the concentrations of chloride led to an increase in the apparent Vmax without affecting the KT. Synaptosomes preincubated with [3H]-L-glutamate exhibit an efflux of the radiolabel, which was stimulated by a substrate for the carrier in the incubating medium, indicating the bidirectional nature of the transport. The chloride-dependent transfer process is restricted to the brain, and regional and developmental profiles clearly distinguish it from the sodium-dependent high-affinity uptake process for glutamate. Nevertheless, the effects of excitotoxic lesions strongly suggest a neuronal localization of the chloride-dependent transport.

Aging↗
PubMed1987

Co-localization of N-acetyl-aspartyl-glutamate in central cholinergic, noradrenergic, and serotonergic neurons.

An immunohistochemical technique for simultaneously visualizing two different antigens has been used to investigate the presence of the acidic dipeptide, N-acetyl-aspartyl-glutamate (NAAG), in cholinergic, noradrenergic-adrenergic, and serotonergic neurons within CNS. The brain slices were processed sequentially with purified antisera against NAAG and then monoclonal antibody against choline acetyltransferase (ChAT), a marker for cholinergic neurons, or antiserum against dopamine-beta-hydroxylase (DBH), a marker of noradrenergic-adrenergic neurons, or antiserum against serotonin (5HT). Both antigens were revealed by the peroxidase reaction but with different chromogens, which are easily distinguishable. An intense double staining of NAAG-like immunoreactivity (NAAG-LI) and ChAT was observed in the motoneurons of the spinal cord as well as in the several motor components of cranial nerve nuclei including facial, ambiguus, and trigeminal nuclei. A partial colocalization of NAAG-LI and ChAT was evident in the perikarya of the basal forebrain cholinergic system, whereas cholinergic neurons of the medial septum exhibited only sporadic staining for NAAG-LI. A complete coexistence of NAAG-LI and DBH was observed in the locus coeruleus. Most of the other noradrenergic and adrenergic cell groups of the medulla region exhibited substantial co-localization with the exception of the A2 cell group, which was virtually devoid of NAAG-LI. In the dorsal raphe, only a low percentage of serotonergic neurons stained for NAAG-LI. The co-existence of NAAG-LI and serotonin was more evident in the neurons of the median raphe, although the majority of cells failed to show double staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Inhibition of [3H]kainic acid receptor binding by divalent cations correlates with ion affinity for the calcium channel.

Since the neurotoxicity of kainic acid may be due to the opening of membrane channels for calcium ions for (Ca2+), the effects of Ca2+ and other cations were examined on the specific binding of [3H]kainic acid to membranes from the forebrain of the rat. [3H]Kainic acid bound to a high affinity site (KD = 5.6 nM) that was inhibited in a concentration-dependent manner by Ca2+ ions with an IC50 of 3.2 mM. In the presence of 1 mM Ca2+, the KD of the binding of [3K]kainic acid increased to 11.1 nM without any change in the Bmax. The divalent cations, manganese and cobalt, also were potent inhibitors of the binding of [3H]kainic acid, while barium and strontium were much weaker. The inhibitory effects of Ca2+ on the binding of [3H]kainic acid were blocked by the inorganic Ca2+ channel blockers, cadmium and lanthanum. These data suggest that Ca2+ modulates the binding affinity [3H]kainic acid through an allosteric interaction between the binding site on the Ca2+ channel and the kainic acid receptor.

Animals↗
PubMed1987

Characteristics of chloride-dependent incorporation of glutamate into brain membranes argue against a receptor binding site.

Although membrane sites from brain, labelled with [3H]glutamate (Glu) under sodium-free conditions, are thought to represent excitatory receptors, certain anomalous characteristics of the kinetics of apparent binding raised the question of whether transport might contribute to this process, prompting a closer examination of it. Hyperosmolar media and low incubation temperatures (4 degrees C) both led to decreases in the apparent specific binding of [3H]glutamate to membranes from the brain of the rat in the presence of chloride. Furthermore, only 15% of the [3H]glutamate, bound at 37 degrees C, was dissociable when the membranes were then cooled to 4 degrees C. The binding of [3H]glutamate was increased in the presence of certain dipeptides such as L-phenylalanyl-L-glutamate (Phe-Glu); and the binding augmented by the presence of Phe-Glu, was also sensitive to temperature and osmolarity of the incubation buffer. Sonication of membranes in 5 mM glutamate increased the apparent binding of [3H]glutamate and abolished the stimulatory effect of Phe-Glu. These findings are consistent with the hypothesis that chloride-dependent association of [3H]glutamate with membranes from brain reflects, in part, a sequestration process, which may be driven by glutamate exchange.

Animals↗
PubMed1987

An autoradiographic study of the development of [3H]hemicholinium-3 binding sites in human and baboon basal ganglia: a marker for the sodium-dependent high affinity choline uptake system.

The developmental distribution of the sodium-dependent high affinity choline uptake (SDHACU) system has been studied in the caudate and putamen of the baboon and of the human by in vitro autoradiography with the ligand, [3H]hemicholinium-3 [( 3H]HCh3). Our results show that [3H]HCh3 binding sites in the newborn baboon and fetal human neostriatum are localized to patches, and then adopt a 'striosome-like' distribution in the juvenile baboon brain. These findings indicate a reorganization of [3H]HCh3 binding site distribution during the ontogeny of the primate neostriatum.

Acetylcholinesterase↗
PubMed1987

The development of daytime rearing behavior in methylazoxymethanol-treated rats: methodological considerations.

The development of daytime rearing behavior was studied in the offspring of pregnant rats which received injections of methylaxymethanol acetate (MAM) or saline during the 15th day of gestation. MAM and control rats were tested at 10, 15, 20, 25, and 30 days of age. The results indicated that the onset of rearing for both groups appeared at approximately 15 days of age, with no significant differences found between sexes. No rearing deficits were seen in MAM rats through 25 days of age despite the fact that these animals sustained greater than a 50% reduction in telencephalic mass. However, at 30 days of age MAM rats reared for significantly longer periods of time during each episode than did their control counterparts, although the actual number of rears did not differ between groups. The results are discussed in terms of neuroplastic events which follow MAM-induced damage and the need for multivariate research when analyzing rearing behavior.

Animals↗
PubMed1987

Genetic linkage in the mouse of genes involved in Down syndrome and Alzheimer's disease in man.

Recently, the gene encoding the cerebrovascular and neuritic plaque amyloid, a pathologic stigma of Alzheimer's disease (AD), has been molecularly cloned and mapped to human chromosome 21, band q21. Changes in the brains of individuals with trisomy 21 (Down syndrome, DS) over 35 years of age closely resemble AD neuropathology. Genetic homology which exists between human chromosome 21 (HSA 21) and mouse chromosome 16 (MMU 16) has led to the use of mice with trisomy 16 as a model system for studies relevant to DS. Mice with Ts16 exhibit numerous developmental abnormalities that can be correlated with features observed in DS, including neurochemical and neuroanatomic alterations. In this study, we show that the genetic homology between HSA 21 and MMU 16 extends to the gene encoding the amyloid peptide. The homologous mouse gene, designated Cvap, for cerebrovascular amyloid peptide, is localized on MMU 16 band C3----ter, and is in close proximity to both superoxide dismutase-1 (Sod-1), and the protooncogene, Ets-2, two of the genes known to localize to the DS region of HSA 21. Linkage of these genes has been maintained since the divergence of the common ancestor of mouse and man, despite a chromosomal rearrangement which has changed the gene order between the two species. These findings expand the region of HSA 21 with known homology to MMU 16, and provide a genetic basis to suggest that studies of the trisomy 16 mouse, in addition to being relevant to DS, may also clarify the role of abnormal gene expression in AD.

Alzheimer Disease↗
PubMed1987

Glutamate and related acidic excitatory neurotransmitters: from basic science to clinical application.

There is convincing evidence that acidic amino acids, in particular L-glutamate, or substances containing them serve as the major excitatory neurotransmitters in the brain. At least three distinct receptors mediate the excitatory effects of this class of neurotransmitters. Pharmacological studies with agonists and antagonists of these receptors suggest that they may mediate the neurodegenerative consequences of Huntington's disease, status epilepticus, and hypoxemia, and that glutamate receptor antagonists have clinical potential as anticonvulsants, analgesics, and neuroprotective agents.

Animals↗
PubMed1987

Neurochemical and immunocytochemical studies on the distribution of N-acetyl-aspartylglutamate and N-acetyl-aspartate in rat spinal cord and some peripheral nervous tissues.

HPLC analysis of rat spinal cord revealed a uniform distribution of N-acetyl-aspartate (NAA) across both longitudinal and dorsoventral axes. In contrast, ventral cord N-acetyl-aspartylglutamate (NAAG) levels were significantly higher than those measured in dorsal halves of cervical, thoracic, and lumbar segments. Immunocytochemical studies using an affinity-purified antiserum raised against NAAG-bovine serum albumin revealed an intense staining of motoneurons within rat spinal cord. Along with the considerable NAAG content in ventral roots, these results suggest that NAAG may be concentrated in motoneurons and play a role in motor pathways. NAAG was also present in other peripheral neural tissues, including dorsal roots, dorsal root ganglia, superior cervical ganglia, and sciatic nerve. It is interesting that NAA levels in peripheral nervous tissues were lower than those in CNS structures and that NAA levels in ventral roots and sciatic nerve were lower than NAAG levels. These findings further document a lack of correlation between NAAG and NAA levels in both central and peripheral nervous tissues. Taken together, these data demonstrate the presence of NAAG in nonglutamatergic neuronal systems and suggest a more complex role of NAAG in neuronal physiology than previously postulated.

Animals↗
PubMed1986

Rapid regulation of [3H]hemicholinium-3 binding sites in the rat brain.

The effects of various drugs known to affect the sodium-dependent high-affinity choline-uptake system (SDHACU) in the brain were examined for their action upon the [3H]hemicholinium-3 [( 3H]HCh-3) binding site, which is associated with the choline carrier. The [3H]HCh-3 binding sites are affected in a similar way to the SDHACU system. Thus, alterations in the velocity of choline-uptake are mediated through changes in the apparent number of available transport sites at cholinergic terminals.

Animals↗
PubMed1986

Basal forebrain neurons provide major cholinergic innervation of primate neocortex.

In 3 monkeys, lesions were made in the basal forebrain by microinjections of ibotenic acid into the nucleus basalis. Bilateral samples of multiple neocortical gyri were assayed for the activity of choline acetyltransferase. Compared to control hemispheres, enzyme activity was reduced up to 69% in the neocortex ipsilateral to the lesion; in addition, acetylcholinesterase staining was decreased at the lesioned site and in the ipsilateral cortex. These results support the concept that the principal cholinergic innervation of the primate neocortex is derived from axons and nerve terminals of neurons whose perikarya are located in the basal forebrain, particularly the nucleus basalis.

Animals↗
PubMed1986

Nicotinic acetylcholine binding sites in Alzheimer's disease.

In Alzheimer's disease (AD), there is a loss of presynaptic cholinergic markers in the cerebral cortex, but the nature of cholinergic receptor changes is unclear. In this study, [3H]acetylcholine and [3H]nicotine were used to label nicotinic cholinergic binding sites in cerebral cortical tissues obtained at autopsy from patients with AD and from matched controls. A consistent and severe loss of nicotinic receptors was found in AD.

Acetylcholine↗
PubMed1986

Anatomical predictors of behavioral recovery following fetal striatal transplants.

The ability of fetal striatal transplants to reverse behavioral deficits produced by kainic acid striatal lesions was assessed in adult female rats. Three groups of animals, including a lesion-only, a lesion and transplant, and a control group were assessed on several measures, including rewarded alternation, a sensorimotor neurological examination and on spontaneous locomotor activity. Anterior-medial striatal lesions led to a decreased performance on the rewarded alternation and sensorimotor neurological examination and caused the animals to be hyperactive in horizontal and stereotypical movements. The transplants partially reversed the rewarded alternation and locomotor deficits, but had little effect on the sensorimotor neurological deficit. Histologically, the transplanted fetal tissue survived well within the kainate-treated striatal region, and partially reversed the lesion-induced cell loss. Neuronal cell counts successfully predicted outcome on several of the behavioral measures, suggesting that the extent of behavioral recovery depends partially on quantitative aspects of the transplantation methodology.

Animals↗
PubMed1986

Heterogeneity of sodium-dependent excitatory amino acid uptake mechanisms in rat brain.

The pharmacologic and kinetic characteristics of sodium-dependent uptake of [3H]L-glutamate, [3H]D-aspartate, and [3H]L-aspartate into crude synaptosomal preparations of rat corpus striatum and cerebellum have been examined in vitro. In cerebellum the apparent Kts and Vmax for the three excitatory amino acids were identical whereas in striatal synaptosomes, the Vmax for [3H]L-glutamate was 30% greater (P less than or equal to .001) than for [3H]D-aspartate and 50% greater (P less than or equal to .001) than for [3H]L-aspartate. L-Amino adipic acid inhibited the uptake of the three amino acids in both regions of brain was 15- to 20-fold more potent in cerebellum than in striatum. In contrast, dihydrokainic acid inhibited transport processes in the corpus striatum but was without activity in cerebellar preparations. The neurotoxin kainic acid blocked only a portion (60%) of [3H]L-glutamate and [3H]D-aspartate uptake in cerebellum while completely inhibiting amino acid transport in corpus striatum. Three days post kainic acid lesion, [3H]D-aspartate uptake was attenuated more than [3H]L-glutamate uptake in the corpus striatum; destruction of corticostriatal afferents reduced [3H]L-glutamate to a greater extent than [3H]D-aspartate. Various lesions of the cerebellum affected excitatory amino acid transport processes to a similar extent. These results suggest that excitatory amino acid transport systems are pharmacologically distinct in different brain regions and may be heterogeneous within a single region.

Animals↗
PubMed1986

A simple method for quantitative electroencephalographic assessment of drugs with convulsant and anticonvulsant properties.

A simple, inexpensive and reliable microcomputer-assisted method to detect and quantify abnormal EEG spiking is described. High frequency wave forms (20-40 Hz) with high amplitude are discriminated using a beta-2 bandpass filter and a threshold comparater. The spikes are then compiled and reported by an Apple II+ microcomputer. The method was validated by measuring seizures generated by intraperitoneal injection of pentylenetetrazol (PTZ), by microinjection of excitatory amino acids into the dorsal hippocampus, and by the antagonism of these seizures by diazepam and 2-amino-7-phosphono heptanoic acid, respectively.

2-Amino-5-phosphonovalerate↗
PubMed1986

Methylazoxymethanol acetate cortical hypoplasia alters the pattern of stimulation-induced behavior in neonatal rats.

In an attempt to identify a neural basis for the developmental progression in the organization of behavior evidenced in responses to lateral hypothalamic electrical stimulation, the responses to medial forebrain bundle (MFB) stimulation of pups whose mothers had been treated with saline or the antimitotic agent methylazoxymethanol acetate (MAM) on gestational Day 15 were measured. Administration of MAM at this age produces a severe and lasting cortical hypoplasia. Monopolar stainless-steel electrodes aimed at the MFB at the level of the lateral hypothalamus were implanted in pups 3, 10, 15 and 20 days of age and responses to 500 ms trains of stimulation were recorded. At 3 and 10 days of age, the number of behavioral responses increased with increasing frequency of stimulation in both MAM and saline-treated pups. Ten-day-old MAM-treated pups, however, displayed 'significantly less behavioral organization in their pattern of responding to stimulation. MAM pups, unlike saline-treated pups, continued to respond to stimulation at Day 15. Even at postnatal Day 20 some MAM-treated pups responded to stimulation. Neurochemical analysis of the brains of littermates demonstrated a significant increase in choline acetyltransferase levels indicating a relative hyperinnervation of afferent cholinergic terminals, confirming the cortical hypoplasia and replicating earlier work. These results suggest a role for the developing neocortex in organizing the behavioral responses to stimulation. The onset of cortical inhibitory mechanisms may channel behavioral responses in normally developing pups and prevent the characteristic activational responses to stimulation in Day-15 pups.

Animals↗