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Biomedical subjects

E D Bird

Publications and source records attributed to E D Bird.

At least 91 records · Page 5Linked to original sources
PubMed1985

The effects of a single acute dose of dexamethasone on monoamine and metabolite levels in rat brain.

Twenty male Sprague-Dawley rats were injected intraperitoneally with either 20 micrograms of dexamethasone or an equivalent volume of saline. The rats were then sacrificed at either one or four hours after the injections and their brains analyzed for monoamine and metabolite content using High Performance Liquid Chromatography with Electrochemical Detection. Significant effects were seen in dopaminergic and serotonergic systems, but these effects varied depending on the area of rat brain studied. Significant increases in dopamine (DA) levels were seen in the hypothalamus and nucleus accumbens of the dexamethasone treated rats when compared with saline treated rats. There was no significant effect of dexamethasone on DA levels in frontal or striatal brain areas. In the dexamethasone treated rats a significant increase in serotonin (5-HT) was observed in the hypothalamus; a significant decrease in 5-HT was observed in the frontal cortex. Biological and clinical implications of these findings are discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Quinolinic acid phosphoribosyltransferase in human and rat brain: activity in Huntington's disease and in quinolinate-lesioned rat striatum.

Quinolinic acid (QUIN) is an excitotoxic compound which is present in rat and human brain and has been hypothetically linked to neurodegenerative disorders including Huntington's disease (HD). We have examined the biochemistry of QUIN by measuring the activity of its degradative enzyme QUIN phosphoribosyltransferase (QPRT) in post-mortem samples of human brain from normal and HD subjects, and in the striata of rats injected intrastriatally with QUIN. In normal human brain, QPRT activity was highest in the caudate nucleus and substantia nigra, less in the thalamus, hypothalamus, frontal cortex and hippocampus and lowest in the spinal cord and cerebellum. QPRT activity in HD caudate tended to be higher than control, the respective values (mean +/- S.E.M., n = 9 for each group) being 365.7 +/- 52.5 and 242.0 +/- 50.8 fmol/h/mg protein (0.1 greater than P greater than 0.05, t-test); values of enzyme activity in the putamen were similar between normal and HD groups. Kinetic analyses indicated that the Km values for QUIN and its co-substrate phosphoribosylpyrophosphate (PRPP) were similar in normal and HD caudate, but Vmax values were elevated in HD caudate. Rat striatal QPRT activity was increased in QUIN-injected striata, and when expressed as a percentage of the contralateral side it was 163.6% at 2 days, 344.4% at 14 days and 198.8% at 7 months post-injection. Kinetic analyses in the 7-month QUIN-injected group showed an increase of Vmax but no change of Km values for QUIN or PRPP. The results indicate that QPRT activity increases in response to specific neurodegenerative events.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

Immunoreactive somatostatin-28(1-12) is increased in Huntington's disease.

Somatostatin-28(1-12) concentrations were measured in Huntington's disease (HD) postmortem tissue using a specific radioimmunoassay. Concentrations of immunoreactive somatostatin-28(1-12) were significantly increased in the caudate and putamen but were unchanged in cortical areas A9 and A17. Since somatostatin-28(1-12) terminates with the amino acids Arg-Glu-OH, we examined whether this dodecapeptide compound might exert a neurotoxic effect. Injections of somatostatin-28(1-12) into rat striatum showed no evidence of histologic damage.

Adolescent↗
PubMed1985

Acetylcholinesterase staining of the human amygdala.

This paper describes in detail the acetylcholinesterase (AChE) staining characteristics of the normal human amygdaloid complex using fixed post-mortem brain tissue. It was shown that the differential AChE staining of the amygdala could be used to accurately delineate amygdaloid subdivisions macroscopically. Using the same staining method on the amygdala from brains previously frozen and stored at -70 degrees C resulted in a staining pattern similar to that seen using fixed tissue, despite numerous ice artifacts. It was concluded that this stain may be useful to researchers working on post-mortem human amygdala, particularly those involved in microdissecting this region for neurochemical analysis.

Acetylcholinesterase↗
PubMed1985

Serotonin and 5-hydroxyindoleacetic acid in CSF. Difference in Parkinson's disease and dementia of the Alzheimer's type.

Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the sixth, 13th, and 20th milliliters of CSF in patients with dementia of the Alzheimer's type (DAT) and Parkinson's disease (PD), and in an aliquot of CSF in controls. In patients with PD there was a positive correlation between 5-HT and 5-HIAA levels in the 20th milliliter of CSF, while in patients with DAT there was a negative correlation of these levels in this CSF fraction. In patients with the senile form of DAT the 5-HIAA levels in the 20th milliliter of CSF were higher than in patients with PD. These results indicate differential involvement of the serotoninergic system in DAT and PD, and may lead to the development of a chemical marker for DAT.

Aged↗
PubMed1985

A corticosteroid/dopamine hypothesis for psychotic depression and related states.

In recent years, considerable data have emerged that psychotic (delusional) depression is characterized by pronounced increases in hypothalamic-pituitary-adrenal (HPA) axis activity and positive responses to combined treatment with tricyclic antidepressants and antipsychotic (dopamine-blocking) agents. Recently, a number of observations in several species, including man, point to glucocorticoids' increasing dopamine activity in a variety of tissues and this effect is particularly marked in rat brain mesolimbic dopamine systems. We propose that glucocorticoids' enhancement of dopaminergic activity may explain the development of psychosis/delusions in the context of the depressive episode. Data in support of the hypothesis are presented and the identification of possible enzymatic risk factors are discussed. These interactions also have implications for understanding the biology of corticosteroid-induced psychoses in medical patients and some of the psychiatric complications of Cushing's Disease.

Brain↗
PubMed1985

Catecholamine metabolites and cyclic nucleotides in cerebrospinal fluid in dementia of Alzheimer type.

Three, 4-dihydroxyphenylacetic acid (DOPAC); 3-methoxy, 4-hydroxyphenylacetic acid (HVA); 3-methoxy; 4-hydroxyphenylglycol (MHPG); adenosine 3', 5'-cyclic monophosphate (cyclic AMP); and guanosine 3', 5'-cyclic monophosphate (cyclic GMP) were measured in cerebrospinal fluid (CSF) of patients with dementia of Alzheimer type (DAT) and controls. DOPAC levels were lower and HVA levels were higher in DAT patients than in controls. In the most rostral fractions of CSF from DAT patients there was a negative correlation between DOPAC and cyclic AMP levels. In addition, patients with onset of DAT symptoms before the age of 65 had lower DOPAC levels, a higher HVA/DOPAC ratio, and higher cyclic nucleotide levels than patients with late onset of DAT. By combining DOPAC and cyclic AMP levels, we could clearly distinguish these two groups.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Neuropathological classification of Huntington's disease.

In postmortem brain specimens from 163 clinically diagnosed cases of Huntington's disease (HD) the striatum exhibited marked variation in the severity of neuropathological involvement. A system for grading this severity was established by macroscopic and microscopic criteria, resulting in five grades (0-4) designated in ascending order of severity. The grade correlates closely with the extent of clinical disability as assessed by a rating scale. In five cases of clinically diagnosed HD there were no discernible neuropathological abnormalities (grade 0), suggesting that the anatomical changes lag behind the development of clinical abnormalities. In eight cases, neuropathological changes could only be recognized microscopically (grade 1). The earliest changes were seen in the medial paraventricular portions of the caudate nucleus (CN), in the tail of the CN, and in the dorsal part of the putamen. Counts of neurons in the CN reveal that 50% are lost in grade 1 and that 95% are lost in grade 4; astrocytes are greatly increased in grades 2-4. These studies indicate that analyses of the CN in grade 4 would reflect mainly its astrocytic composition with a component of remote neurons projecting to the striatum. Because of the relative preservation of the lateral half of the head of the CN in grades 1-2, these regions would reflect early cellular and biochemical changes in HD.

Caudate Nucleus↗
PubMed1985

Regional mitochondrial respiratory activity in Huntington's disease brain.

This study investigated mitochondrial respiratory activity in Huntington's disease (HD) brain. Mitochondrial membranes from caudate and cortex of HD and non-HD autopsied brains were assayed for succinate oxidation, cytochrome oxidase activity, and cytochromes b, cc1, and aa3. There was a significant decrease in HD caudate mitochondrial respiration, cytochrome oxidase activity, and cytochrome aa3, whereas cytochromes b and cc1 were normal. These findings are consistent with the hypothesis that mitochondrial dysfunction may contribute to the localized hypometabolism and progressive atrophy of the HD caudate.

Brain↗
PubMed1985

Late onset of Huntington's disease.

Twenty-five patients with late-onset Huntington's disease were studied; motor impairment appeared at age 50 years or later. The average age at onset of chorea was 57.5 years, with an average age at diagnosis of 63.1 years. Approximately 25% of persons affected by Huntington's disease exhibit late onset. A preponderance of maternal transmission was noted in late-onset Huntington's disease. The clinical features resembled those of mid-life onset Huntington's disease but progressed more slowly. Neuropathological evaluation of two cases reveal less severe neuronal atrophy than for mid-life onset disease.

Age Factors↗
PubMed1985

Late-onset Hallervorden-Spatz disease presenting as familial parkinsonism.

We studied a 68-year-old man who died after 13 years of progressive dementia, rigidity, bradykinesia, mild tremor, stooped posture, slow and shuffling gait, dystonia, blepharospasm, apraxia of eyelid opening, anarthria, aphonia, and incontinence. At autopsy, he had generalized brain atrophy with large deposits of iron pigment in the globus pallidus, caudate, and substantia nigra. Axonal spheroids were found in the globus pallidus, substantia nigra, medulla, and spinal cord. The neurochemical analysis of the brain revealed marked loss of dopamine in the nigral-striatal areas, with relative preservation of dopamine in the limbic areas. This is the oldest case of familial Hallervorden-Spatz disease reported and the first with neurochemical analysis of the brain.

Aged↗
PubMed1985

Cerebrospinal fluid neurotransmitter metabolites in neurologically normal infants and children.

Significant inverse correlations with age were observed for free 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) concentrations in CSF from 75 neurologically normal newborns, infants, and children aged 1 day to 10 years. The concentration of free MHPG decreased rapidly in early neonatal life and was reduced to near adult levels by 8 to 9 months of age. Adult levels of 5-HIAA were observed at about 4 years of age whereas HVA concentrations were still above adult levels at 10 years of age. Data from 0- to 1-month-old premature (28 to 32 weeks of gestation) and full-term (37 weeks of gestation) infants revealed marked changes in HVA and 5-HIAA concentrations which were related to postconceptional rather than postnatal age. This study demonstrates a previously undetected age effect on CSF MHPG concentration during the neonatal period and provides valuable normal data that are necessary for the interpretation of CSF monoamine metabolites in infants and children with hyperphenylalaninemia and other neurologic disease involving monoamine neurotransmitters.

Age Factors↗
PubMed1984

Dexamethasone increases plasma free dopamine in man.

In man, unconjugated plasma DA is normally undetectable or present in minute amounts. Twelve medication-free volunteers received a 1 mg dose of dexamethasone which produced pronounced increases of plasma free DA but not of other catecholamines. Mean plasma free dopamine levels after dexamethasone at 8 a.m. (155 +/- 102 pg/ml) and 4 p.m. (163 +/- 70 pg/ml) were significantly higher (p less than 0.001) than those at 8 a.m. (50 +/- 18 pg/ml) and 4 p.m. (42 +/- 7 pg/ml) before dexamethasone. Although the mechanism of increased dopaminergic activity after a dose of dexamethasone remains for future research, the data presented in this paper may explain the observations that corticosteroids lower prolactin levels and may induce psychiatric disturbances, as well as the finding that depressed patients with high postdexamethasone cortisol levels are frequently psychotic.

Adrenal Cortex Hormones↗
PubMed1984

Somatostatin is increased in the nucleus accumbens in Huntington's disease.

Concentrations of somatostatin-like immunoreactivity (SLI) are elevated in the basal ganglia in Huntington's disease. The present study confirms these findings and, in addition, shows that concentrations of SLI are significantly elevated in the nucleus accumbens (4.04 +/- 0.66 versus 1.69 +/- 0.21 ng/mg protein in controls). This area is relatively spared pathologically and shows little atrophy in Huntington's disease. Since many patients with Huntington's disease are treated with haloperidol, we studied the effects of this drug in rats. There was a dose-dependent reduction of SLI in striatum, parietal cortex, and hippocampus. The elevated concentrations of SLI in the basal ganglia in Huntington's disease, therefore, do not appear to result from haloperidol therapy.

Adolescent↗
PubMed1984

The effect of manganese inhalation on basal ganglia dopamine concentrations in rhesus monkey.

Manganese (Mn) may produce neurotoxicity in man through inhalation of Mn dust. Animals exposed to excessive Mn develop neurological abnormalities, and neuropathological lesions in the brain mainly in the globus pallidus with decreased concentrations of the neurotransmitter, dopamine (DA), in the brain. Monkeys exposed to Mn by inhalation did not produce any abnormal movements. After two years, the animals were sacrificed and certain brain areas were compared to controls. There were significant decreases in DA concentration in caudate and globus pallidus, and there was a 60-80% increase in Mn concentration in the basal ganglia of the brain. The DA system in the basal ganglia is vulnerable to the effects of Mn, but the amount of Mn inhaled and the period of exposure would appear to determine whether abnormal neurological signs develop.

Animals↗
PubMed1983

Decreased catecholamine content caused by slicing of frozen human post mortem brain with an electric blade.

A deleterious effect on dopamine and norepinephrine levels was observed in cortical Brodmann area 25 tissue dissected from mechanically cut coronal slices of frozen human brain. Catecholamine concentrations were found to be 10 (NE) and 7 (DA) fold higher in similar tissue dissected directly from the frozen hemisphere without cutting. A heat-related breakdown in endogenous catecholamine content is suspected. An alternative method is presented for cutting coronal slices of frozen human brain which involves much less heat and friction and provides slices with excellent morphological appearance.

Brain Chemistry↗