Search PubMed⌕ Search

Biomedical subjects

P A Shea

Publications and source records attributed to P A Shea.

At least 19 recordsLinked to original sources
PubMed1993

Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation.

Lesions of the cholinergic nucleus basalis of Meynert elevate the ex vivo synthesis of beta amyloid precursor protein (beta-APP) in the cerebral cortex, a major projection region. We have found that this elevation is reflected by increased levels of beta-APP mRNA. The induction is rapid (occurring 60 min after placement of the lesion) and persistent (remaining for at least 45 days after lesioning). Two other subcortical lesions, which result in reductions of cortical adrenergic and serotonergic innervation, similarly induced cortical beta-APP. The beta-APP induction is reversible and does not require loss of the subcortical neurons. Infusion of lidocaine, a calcium antagonist that disrupts neurotransmitter release, into the nucleus basalis of Meynert leads to the temporary reduction of released acetylcholine in the cortex. In this model, beta-APP mRNA levels are elevated shortly after the infusion of lidocaine (90 min) but return to preinfusion levels 7 days after the lidocaine treatment. However, metabolic stresses of the brain, including chronic physostigmine, glucocorticoid, and diabetogenic treatments, fail to induce the beta-APP response. These results suggest that the induction of beta-APP is a specific response to the loss of functional innervation in the cortex. Importantly, these studies show that cortical beta-APP is induced by lesions that mimic the neurochemical deficits most frequently observed in Alzheimer disease.

5,7-Dihydroxytryptamine↗
PubMed1983

Serotonergic changes in specific areas of rat brain associated with activity--stress gastric lesions.

To study serotonergic involvement in the development of gastric lesions following activity wheel stress, three groups of rats (gastric lesions, no gastric lesions, and home--cage controls) were killed following exposure to the experimental procedures. The brains were dissected into eight specific areas and subjected to analyses for serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) using high performance liquid chromatography with EC detection. Lower levels of 5-HT were found in the midbrain, cortex, and hippocampus of rats with gastric lesions compared to either the no lesion group, subjected to shorter periods of activity--stress, or the home--cage control group. Levels of 5-HT and 5-HIAA were elevated in the pons/medulla oblongata of both the lesion and the no lesion groups compared to the home--cage controls. Corticosterone levels in blood were also significantly elevated in the lesion group. These data on serotonin changes in the CNS suggest a possible role for this neurotransmitter in stress-induced gastric pathology.

Animals↗
PubMed1982

A rapid and simple method to determine the specific activities of serotonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan in brain by HPLC with electrochemical detection.

The specific activities of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) have been determined in the brain of rats by HPLC using electrochemical detection. The method allows, from a single sample, the simultaneous measurement of all three compounds and collection of each peak for radioactivity determinations. Five male Wistar rats were injected i.v. with 2.0 mCi/kg of DL-5-hydroxy-[G-3H]tryptophan (2.6 Ci/mmol) and 30 min later the animals were killed by near freezing. Whole brains were removed and homogenized in an acid medium. The content of 5-HTP, 5-HT, and 5-HIAA were determined by HPLC. Each peak of interest was immediately collected after detection in scintillation vials by use of a small dead space detector (TL-9A, Bioanalytical Systems, Inc.). The amounts of radioactivity were determined and specific activities calculated from the results. A second chromatography system (TLC) was used to check the authenticity and purity of compounds separated by the HPLC.

5-Hydroxytryptophan↗
PubMed1982

Effects of streptozotocin diabetes on the noradrenergic innervation of the rat heart: a longitudinal histofluorescence and neurochemical study.

The effects of the age of induction and total duration of streptozotocin diabetes on the sympathetic noradrenergic innervation of the rat heart was examined with glyoxylic acid induced histofluorescence to demonstrate the distribution of noradrenergic fibers within the heart, and with high performance liquid chromatography with electrochemical detection to measure tissue levels of the neurotransmitter norepinephrine. Diabetes was induced in male Sprague-Dawley rats at 1, 2, and 4 months of age. Within each of these groups, diabetic rats survived for periods of 1, 2, and 4 months. Additional groups of diabetic rats survived to a chronological age of 8 months. Norepinephrine levels in the hearts of diabetic rats were increased over those of control rats in all groups at 1 month duration of diabetes. Ventricles were generally affected to a greater extent than atria. At 2 months duration of diabetes, ventricular levels remained elevated while atrial norepinephrine levels were at or below control levels. At 4 months duration of diabetes, and in all groups at 8 months of age, the norepinephrine levels were at or below control levels, except in the ventricles of rats induced at 4 months of age, which remained elevated. Histofluorescence studies demonstrated the presence of axon bundles and varicose noradrenergic profiles in the diabetic rat hearts, distributed in a pattern similar to that seen in controls. However, at 1 month duration of diabetes in all groups, the density of noradrenergic varicosities in diabetic rat hearts appeared increased with abundant branched profiles. These results are surprising, since studies on genetic models of diabetes have suggested decreased norepinephrine levels in the heart. The present study suggests that during the early phases of streptozotocin induced diabetes, noradrenergic nerves are still intact and may be susceptible to pharmacologic manipulation. The later fall of norepinephrine levels back to or below control levels may indicate actual neuronal damage, suggesting that early intervention may be necessary to protect these nerves from degeneration. This issue is potentially important in view of the reported toxic effects of high NE levels on the heart, and the high incidence of death from myocardial infarct in diabetic humans with autonomic neuropathy.

Animals↗
PubMed1982

The relationship between plasma and red blood cell neuroleptic levels, oral dosage, and clinical parameters in a chronic schizophrenic population.

Neuroleptic drug levels were determined in plasma and RBC in 63 subjects on various neuroleptic drugs using a radioreceptor binding assay. There was a correlation between oral dose in chlorpromazine equivalents and plasma level (r = 0.31, p less than .01). The correlation between dose and plasma level and ratios of plasma level to dose varied by drug. RBC neuroleptic concentration was not related to dosage. In a group of 25 chronic schizophrenic inpatients, plasma level was significantly curvilinearly related to total BPRS. For subjects with plasma levels below 25 ng haloperidol/ml, BPRS total and thought disorder subscores were negatively correlated to plasma level (p less than 0.02). RBC drug concentration was not related to psychopathology. For six of seven subjects, changes in medication based on plasma level resulted in some clinical improvement. Data are presented on the inter- and intraassay variability and other factors which affect the clinical usefulness of the radioreceptor assay.

Administration, Oral↗
PubMed1981

Plasma tryptophan and five other amino acids in depressed and normal subjects.

Decreases in brain serotonin levels have been implicated in the pathogenesis of human depression. While circulating levels of tryptophan (TRP) might possibly reflect concentration of brain serotonin, a more relevant peripheral measure may be the ratio of plasma TRP to five other neutral amino acids (TRP/5aa ratio). In depressed subjects and normal controls, plasma TRP (free and total), phenylalanine (PHE), tyrosine (TYR), leucine, isoleucine, and valine were measured on three days. When depression was most severe, depressed patients had lower TRP/5aa ratios and total TRP levels and higher PHE and TYR levels. After the patients' conditions improved, these differences disappeared. As Hamilton depression scores improved, the plasma TRP/5aa ratios increased significantly. This finding tends to support the idea that changes in brain serotonin level reflect changes in depression severity.

Amino Acids↗
PubMed1981

Sympathetic innervation of murine thymus and spleen: evidence for a functional link between the nervous and immune systems.

Sympathetic innervation was demonstrated in both perivascular and parenchymal regions of murine thymus and spleen. Catecholamine varicosities were associated with mast cells in these areas. The antibody response to sheep red blood cells of 7 week old mice that had been sympathectomized with six-hydroxydopamine (6OHDA) at birth was significantly elevated compared with saline treated controls. Alpha-methyl tyrosine (alpha-MT) and 6OHDA treatment of mice, producing a more complete sympathectomy, showed a significantly enhanced anti-SRBC response with respect to mice treated with alpha-MT or 6OHDA alone. Catecholamine levels in thymus, spleen, and adrenals of both experimental and control mice were measured using liquid chromatography with electrochemical detection (LCEC). The present study suggests that the sympathetic nervous system has a functional role in modulating the humoral immune response in vivo.

Adrenergic Fibers↗
PubMed1981

Elevation of choline and glycine in red blood cells of psychiatric patients due to lithium treatment.

Levels of choline (Ch) and glycine (Gly) were determined in red blood cells (RBC) from psychiatric patients who were either on lithium therapy or lithium-free and normal subjects. Subjects were divided into four groups: normal subjects who have never received Li+; Li+ free affective patients; Li+ free patients with various psychiatric disorders; and affective patients under Li+ treatment. The patient groups included affective, schizophrenic, schizo-affective disorders, as well as patients with organic brain syndrome and Cornelia de Lange syndrome. In general, all patients on therapeutic dosages of Li+ had significantly higher levels of Ch in RBC when compared to Li+ free normals or patients. Glycine levels in RBC were also significantly higher in patients on Li+ compared to normals or Li+ free affective disorder patients. Plasma Ch was significantly elevated in patients receiving Li+. There was an apparently predictable time course between cessation of Li+ therapy and decreases in levels of Ch and Gly in RBC to normal levels; in Ch of approximately 30-40 days, in Gly of less than 6 days. There were no significant differences in Ch between Li+ free patients, irrespective of their disorder, and normal subjects. RBC Gly levels were equivalent between normal subjects and Li+ free patients. These data imply that elevations in Gly and Ch are more a function of Li+ therapy than of psychiatric diagnosis.

Adult↗
PubMed1979

HPLC determination of biogenic amines in discrete brain areas in food deprived rats.

Norepinephrine (NE), dopamine (DA), 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) levels in the lateral hypothalamus (LH), ventromedial hypothalamus (VMH), median raphe (MR) and dorsal raphe (DR) were determined in nondeprived and 48 hr food deprived rats. Simultaneous determination of these compounds was accomplished by means of high performance liquid chromatography (HPLC) with electrochemical detection. When compared with controls, food deprived animals showed significant increases in 5-HT and 5-HIAA levels in the raphe nuclei, significant increases in 5-HIAA in the LH, but no changes in either 5-HT or 5-HIAA levels in the VMH. No changes in catecholamine levels were found in any of the brain areas studied. These results show that indoles in the raphe nuclei, as well as in the LH, are affected by food deprivation. The lack of change in indole levels in the VMH indicates that specific nuclei within the hypothalamus are differentially affected by food deprivation.

Animals↗
PubMed1976

Cholinergic changes during conditioned suppression in rats.

Levels of acetylcholine were significantly elevated in the telencephalon and diencephalon + mesencephalon of rats killed by near-freezing during conditioned suppression of food-reinforced lever pressing, whereas levels of serotonin, dopamine, and norepinephrine were not altered. These neurochemical changes were not seen in rats serving as controls for conditioning experience, activity levels, or stimulus presentation.

Acetylcholine↗