PubMed Health⌕ Search

Biomedical subjects

J T Slevin

Publications and source records attributed to J T Slevin.

At least 37 records · Page 2Linked to original sources
PubMed1989

Aberrant guanosine triphosphate-beta-tubulin interaction in Alzheimer's disease.

Guanosine triphosphate (GTP) is an absolute requirement for tubulin polymerization in situ. The nucleotide photoaffinity probe 8-azidoguanosine 5'-triphosphate (8N3GTP) has been shown to be a biological mimic of GTP in this system and, also, an effective active site probe of the exchangeable GTP binding site. Using [32P]8N3GTP we demonstrate that the exchangeable GTP site of the beta subunit of tubulin is available to added guanine nucleotide in normal aged brain homogenates, whereas it is variably unavailable in Alzheimer's diseased brain. Inability of 8N3GTP to photolabel beta tubulin appears to be associated with neurofibrillary tangle density. These results support the hypothesis that microtubule formation is abnormal in brains affected by Alzheimer's disease.

Aged↗
PubMed1989

Substantia nigra 6-hydroxydopamine lesions alter dopaminergic synaptic markers in the nucleus basalis magnocellularis and striatum of rats.

Recent findings have demonstrated the existence of dopaminergic (DA) markers in the nbM of the human brain and a reduction of these markers in both the nbM and the striatum of patients suffering from Alzheimer's disease (AD). To investigate the source of the DA synaptic markers found in the nbM, rats received unilateral 6-OHDA lesions of the substantia nigra pars compacta (SNc). The SNc lesions caused significant reductions in DA and DOPAC but not HVA in the nbM and the striatum; 3H-sulpiride binding to D2 receptors ipsilateral to the SNc lesion was significantly increased in the striatum (16%), consistent with denervation supersensitivity, but single-point analysis showed no significant changes in the nbM. These data suggest that the decreases in DA and 3H-spiperone binding levels observed in the nbM of AD patients may be due to partial destruction of DA nbM afferent projections from the brainstem.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Long-term enhancement of K+-evoked release of L-glutamate in entorhinal kindled rats.

Kainic acid- and K+-evoked in vitro release of endogenous amino acids from hippocampal slices were measured in rats kindled by entorhinal electrical stimulation. One month after completion of kindling, K+-evoked release of glutamate from hippocampal slices ipsilateral to the stimulus site was consistently greater than from both the contralateral hippocampus from kindled animals and all hippocampi of electroshock and sham-surgery control groups. Enhanced hippocampal neurotransmitter glutamate release may be involved in the permanent effects of electrical kindling.

Animals↗
PubMed1987

Amygdalar kindling is associated with elevated zinc concentration in the cortex and hippocampus of rats.

The reported convulsant properties of zinc and its association with hippocampal function prompted investigation of zinc levels during the induction and maintenance of kindling. Rats were fed zinc adequate diets during kindling, incited by daily amygdalar stimulation. The concentration of zinc in hippocampus was unperturbed during 3 stages of kindling induction when compared to either naive, sham surgery, or electroshock controls. In contrast, cortical zinc increased during kindling induction but returned to control levels in fully kindled animals. Two weeks after full kindling was established, the concentration of zinc in the hippocampus and overlying cortex increased significantly, in the absence of further electrical stimulation. The effect was restricted to the central nervous system inasmuch as zinc levels were unaffected in liver and other extracerebral tissues. Moreover, the zinc concentration was relatively unchanged during the 24 h period following a single electroconvulsive seizure, implying that the observed changes were not simply a postictal phenomenon. The results of this study suggest that long-lasting elevations in zinc are present after kindling is established. Whether this finding is related to the perpetuation of abnormal neuronal excitability or represents a compensatory response remains to be elucidated.

Amygdala↗
PubMed1987

Altered striatal dopaminergic metabolism 36 hours after unilateral trauma to the human mesencephalon.

Markers of dopaminergic synaptic activity and choline acetyltransferase (CAT) were measured in the putamen and caudate nucleus of a patient who lived 36 hours after a unilateral mechanical lesion of the mesencephalon. After cessation of impulse flow along the nigrostriatal tract, dopamine was elevated, dihydroxyphenylacetic acid was diminished, and CAT and tyrosine hydroxylase activity were enhanced in the putamen ipsilateral to the lesion. [3H]-spiperone binding indicated an increase in D2-dopamine receptor density in the caudate nucleus. These findings indicate that the changes predicted from experimental neurochemical models occur in human nigrostriatal systems.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Alzheimer's disease: monoamines and spiperone binding reduced in nucleus basalis.

Levels of dopamine and serotonin, and of their precursors and metabolites, were measured in the nucleus basalis of Meynert (nbM) of patients with Alzheimer's disease and control patients. [3H]Spiperone binding to membrane homogenates of the nbM, indicative of both dopaminergic and serotonergic receptors, was also measured. The nbM from patients with Alzheimer's disease showed significant decreases in both spiperone binding and in the levels of dopamine and serotonin but no decrease in either tyrosine or tryptophan levels. These data indicate a loss of both dopaminergic and serotonergic synapses in the nbM of patients with Alzheimer's disease.

Aged↗
PubMed1986

Stability of sialogangliosides in kindled hippocampus.

Altering ganglioside concentration can modulate L-[3H]glutamic acid binding to synaptic membranes in vitro. This study indicates that a recently reported increase of hippocampal L-glutamate receptor density observed with entorhinal kindling is not associated with a quantitative change in hippocampal neuronal membrane sialoganglioside.

Animals↗
PubMed1986

3-Methoxytyramine in the putamen as a gauge of the postmortem interval.

The armamentarium of the forensic thanatologist includes the examiner's subjective assessment of bodily changes together with comprehensive evaluation of environmental and associated factors to estimate the postmortem interval (PMI). Of the various objective means, postmortem accumulation of potassium in vitreous humor is a widely used gauge. In view of the considerable variability inherent in these techniques, an additional marker with greater accuracy would be a welcome supplement to these indices. We have developed a method of estimating PMI from the level of 3-methoxytyramine (3-MT) in the dorsal putamen of the brain. The supernatant of a sample of putamen, sonicated in 6 volumes (weight/volume) of 0.1 M perchloric acid and centrifuged at 51 000 times gravity for 10 min, was analyzed for 3-MT using high-pressure liquid chromatography with electrochemical detection. The change of 3-MT in the putamen is linearly related to the PMI (range: 5.5 to 60 h), irrespective of patient age (1 to 84 years). This observation is attributable to several factors, including high substrate (dopamine) concentration, preservation of catechol-O-methyl transferase activity, and an inactivation of monoamine oxidase activity, as a result of a decrease in tissue pO2.

Adolescent↗
PubMed1985

Effects of zinc on markers of glutamate and aspartate neurotransmission in rat hippocampus.

Receptor binding and synaptosomal uptake of L-[3H]glutamate and L-[3H]aspartate were measured in hippocampus derived from rats maintained on zinc restricted diets from weaning. Despite near lethal zinc deficiency, these markers of excitatory amino acid neurotransmission were unaffected compared to zinc-supplemented controls. However, addition of zinc in vitro markedly inhibited binding of glutamate and aspartate to hippocampal membranes. These data suggest that zinc can modulate the receptor affinities for glutamate and aspartate and may function as a tonic inhibitor of excitatory synapses in vivo.

Animals↗
PubMed1985

Determination of tyrosine, tryptophan and their metabolic derivatives by liquid chromatography-electrochemical detection: application to post mortem samples from patients with Parkinson's and Alzheimer's disease.

A procedure is described for the rapid determination of the major indoles and catechols. Analysis with picogram detection limits was done by high-pressure liquid chromatography on a C18 reverse-phase column using electrochemical detection (LCEC). This method provides a comprehensive list of compounds which can be simultaneously determined in brain samples and for which there is no necessity of derivatization or pre-column purification. The regional distribution of 9 neurochemicals from rat brain and the levels of 10 neurochemicals from human brain are presented. DOPA, TYR, NE, MHPG, DOPAC, 5-HIAA, TRP, DA, HVA, 3-MT and 5-HT were detected in the caudate nucleus and putamen. The levels of neurochemicals from the caudate and putamen of a demented patient with Parkinson's disease were variably decreased; catechol and indole losses were greatest in the putamen. The levels of neurochemicals in the caudate and putamen of patients with Alzheimer's disease (SDAT) were also variably decreased; loss of NE was seen only in putamen and losses of DA, HVA and 5-HT were uniform across both caudate and putamen. The CSF of SDAT patients showed changes in NE only.

Aged↗
PubMed1985

Lack of effect of entorhinal kindling on L-[3H]glutamic acid presynaptic uptake and postsynaptic binding in hippocampus.

Sodium-independent L-[3H]glutamic acid binding and sodium-dependent L-[3H]glutamic acid high affinity uptake were measured in hippocampal membranes of rats administered electroshock seizures or kindled to class 5 seizures by entorhinal cortical stimulation. There were no differences in these glutamatergic synaptic markers among electroshocked, kindled, or surgical control animals. Entorhinal kindling is not a reflection of activity-regulated facilitation of perforant path glutamatergic neurotransmission.

Animals↗
PubMed1985

Age-associated alteration of serotonergic synaptic neurochemistry in rat rostral hypothalamus.

Levels of monoamines and metabolites in rostral and caudal hypothalamic fragments of young (3-4 months) and old (25-26 months) Fischer 344-rats were compared. There were no differences between fragments of young animals. In senescent rats, 5-hydroxyindoleacetic acid (5HIAA) increased in both rostral and caudal hypothalamus. The ratio 5HIAA/5HT (serotonin), an index of serotonin turnover, increased only rostrally. This age-related increase of 5HIAA/5HT in rostral hypothalamus was associated with a decrease in [3H]-spiperone binding. There were no age-related changes of MAO-A activity in the hypothalamus or of serum tyrosine or tryptophan levels.

Aging↗
PubMed1985

Chronic valproic acid therapy and synaptic markers of amino acid neurotransmission.

Valproic acid acutely alters regional brain concentrations of GABA and of aspartic and glutamic acids in vivo, and it potentiates the action of these amino acid neurotransmitters on neurons in vitro. Chronic alterations of presynaptic uptake or receptor binding activity induced by these effects of valproate could contribute to its anticonvulsant properties. We treated rats with valproate (100 mg/kg ip bid) for 3 weeks; drug levels in frontal cortex reached 70 micrograms/g tissue, but there was no effect on uptake and binding activity of these amino acids in cortex and hippocampus.

Animals↗
PubMed1983

Analogue interactions with the brain receptor labeled by [3H]kainic acid.

The kinetics of interaction of kainic acid analogues and reputed antagonists of acidic excitatory amino acids with a specific binding site for [3H]alpha-kainic acid were examined in washed cerebellar membranes incubated at 4 degrees C. The avidity of both L-glutamate (1.5 microM) and quisqualate (0.6 microM) suggests that proper orientation of the two carboxyls in the amino group is essential for binding to one component of the receptor. The high affinity of domoate, alpha-kainate and alpha-keto-kainate as compared to the low affinity of dihydrokainate and alpha-allo-kainate indicate that a pi electron group with appropriate cis-planar orientation versus the C2-carboxyl group is essential for high affinity binding to the receptor. These studies provide additional evidence that the recognition site labeled by [3H]kainic acid represents the receptor mediating its neurophysiologic and neurotoxic effects.

Animals↗
PubMed1981

Ontogeny of receptor binding sites for [3H]glutamic acid and [3H]kainic acid in the rat cerebellum.

The development of the specific binding sites for L-[3H]glutamic acid (KD = 370 nM) and for [3H]kainic acid (KD = 39 nM) was studied in the rat cerebellum. Specific binding at both sites remains low during the first week after birth but increases markedly during the second and third weeks after birth, when glutamatergic parallel fiber synaptogenesis occurs. The development of the kainate site lags behind that of the glutamate site, indicating their autonomy.

Aging↗