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Biomedical subjects

A J Cross

Publications and source records attributed to A J Cross.

At least 91 records · Page 5Linked to original sources
PubMed1986

Neuropeptides and dopamine in the marmoset. Effect of treatment with 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP): an animal model for Parkinson's disease?

Neurochemical studies of post-mortem human parkinsonian brains have demonstrated specific alterations in neuropeptide concentrations within the substantia nigra and striatal structures. The drug, 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP) has been reported to act as a selective toxin to nigrostriatal dopamine neurons, and induces a parkinsonian-like syndrome in primates. In this study, marmosets developed features typical of Parkinson's disease following treatment with MPTP for four days. The effects of MPTP treatment on the concentrations of dopamine and neuropeptides were determined and changes compared with those reported for Parkinson's disease. It was found that within the substantia nigra, substance P concentrations doubled following treatment with MPTP; in contrast, concentrations of vasoactive intestinal peptide and neuropeptide Y were significantly reduced. No changes were observed in the concentrations of six other neuropeptides measured in this region, notably cholecystokinin. Despite marked depletion of dopamine within the caudate nucleus and putamen, concentrations of all neuropeptides within these structures remained unchanged with the exception of an isolated reduction of neuropeptide Y within the putamen. Somatostatin concentrations within the frontal cortex and hippocampus were significantly elevated in the marmosets treated with MPTP. These neuropeptide changes in the CNS contrast with those reported for Parkinson's disease. In view of the autonomic dysfunction associated with Parkinson's disease, peripheral concentrations of neuropeptides were determined. Significant depletion of neuropeptide Y was identified in the ureter, adrenal and cardiovascular tissue. Thus the neurochemical changes induced by MPTP may not be as selective as previously reported.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Subclinical infections in mice resulting from the modulation of a lethal dose of Semliki Forest virus with defective interfering viruses: neurochemical abnormalities in the central nervous system.

The lethal encephalitis caused in mice by Semliki Forest virus (SFV) is modulated to a subclinical infection by administration of defective interfering SFV, although virus still multiplies both in the central nervous system (CNS) and systemically. Here we report that such infections result in unique and selective changes in the normal levels of CNS neurotransmitters some of which persist after infectious virus can no longer be detected. This represents a previously undocumented category of infection which may have a bearing on the aetiology of those human neurological and neuropsychiatric diseases to which viruses are believed to contribute.

Animals↗
PubMed1986

Subcellular pathology of human neurodegenerative disorders: Alzheimer-type dementia and Huntington's disease.

Activities of enzyme markers of subcellular organelles have been measured in brain tissue from subjects with Alzheimer-type dementia (ATD) and Huntington's disease (HD). Significant increases in the activity of the lysosomal enzyme beta-glucuronidase were observed in both ATD temporal cortex and HD putamen. It is suggested that beta-glucuronidase activity may be a useful biochemical indicator of cellular damage in the CNS. A significant reduction in neutral alpha-glucosidase activity was observed in ATD temporal cortex and HD putamen. This change may reflect an alteration in glycoconjugate processing and may relate to the susceptibility of neurones to the degenerative processes of ATD and HD.

Aged↗
PubMed1986

N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the monkey: neurochemical pathology and regional brain metabolism.

Systemic administration of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to macaque monkeys induced a profound parkinsonian state marked by hypokinesia/bradykinesia, rigidity and tremor. Postmortem studies revealed severe pathological changes in the substantia nigra, pars compacta and in the ventral tegmental area. The levels of dopamine and its major metabolites were reduced by about 90% in the neostriatum, including the nucleus accumbens, when compared to controls. In one animal, the locus coeruleus showed severe pathological changes in association with a reduction in forebrain noradrenaline. 2-deoxyglucose uptake studies suggested that in experimental parkinsonism there if a profound change in the activity of the striatopallidal pathway, but not necessarily in the striatonigral pathway.

Animals↗
PubMed1985

Sites of the neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the macaque monkey include the ventral tegmental area and the locus coeruleus.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a profound parkinsonian state when systemically administered in monkeys and man. Previous studies have shown MPTP to be toxic to only the dopamine (DA) cells in the substantia nigra pars compacta and not to other catecholamine (CA)-containing cells. The data presented here suggest that MPTP also has a specific neurotoxic effect on the DA-containing cells of the ventral tegmental area and the noradrenaline-containing cells of the locus coeruleus in macaque monkeys with a moderate-to-severe parkinsonian syndrome. The results suggest that MPTP-induced parkinsonism in the monkey more closely replicates the neurochemical changes seen in idiopathic Parkinson's disease than previously thought.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Cortical serotonin receptor subtypes after lesion of ascending cholinergic neurones in rat.

Serotonin (5-HT) S1 and S2 receptors were studied in rat cortex after lesion of the ascending cholinergic systems by injection of ibotenic acid into the nucleus basalis. The lesions produced a large (56%) decrease in choline acetyltransferase activity with no change in markers of gamma-aminobutyric acid, dopamine and 5-HT containing neurones. Lesions of the ascending cholinergic neurones were accompanied by a loss of 5-HT S1 receptor binding sites with no change in S2 receptors. These results suggest that a proportion of S1 receptors may be associated with cholinergic terminals.

Animals↗
PubMed1985

Dissociation of neuropeptide Y and somatostatin in Parkinson's disease.

The concentration of neuropeptide Y has been determined in the cortex and hippocampus of subjects with Parkinson's disease and compared to changes of activity of dopamine beta-hydroxylase and concentration of somatostatin. Despite a marked reduction in the concentration of somatostatin in the severely demented subject, in both cortex and hippocampus, no significant change in concentration of NPY was found in either region. This finding therefore suggests that the majority of NPY within the cortex is independent of somatostatin. This study provides some further evidence of neurochemical similarities between the dementia of Parkinson's disease and Alzheimer's disease.

Brain Chemistry↗
PubMed1985

Chemical and structural changes in the brain in patients with movement disorder.

Neurochemical indices of dopaminergic function were assessed in basal ganglia of post-mortem brains of control subjects and schizophrenic patients who had been rated in life for the presence of movement disorder and neuroleptic intake. In schizophrenics who had been treated chronically with doses of neuroleptics, concentrations of dopamine D2 receptors were significantly increased above controls, whereas dopamine D1 receptors and dopamine metabolism were unchanged. Increased D2 receptors were also observed in basal ganglia of drug-free patients. Concentrations of dopamine D1 and D2 receptors in schizophrenics with movement disorder. Moreover, no relationship was found between dopamine receptor levels and the severity of movement disorder. Concentrations of the dopamine metabolite homovanillic acid were increased in the putamen and nucleus accumbens in a small number of patients with movement disorder compared with controls or patients without movement disorder. No changes were observed in markers of cholinergic and GABA-containing neurones. The present findings are not consistent with a "dopamine receptor hypersensitivity" concept of movement disorder in schizophrenia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Loss of endoplasmic reticulum-associated enzymes in affected brain regions in Huntington's disease and Alzheimer-type dementia.

Post-mortem brain samples from patients with either Huntington's disease, Alzheimer-type dementia or appropriate controls were assayed for endoplasmic reticulum enzymes, NADPH-cytochrome c reductase, neutral alpha-glucosidase, inosine diphosphatase, alpha-mannosidase and glucose-6-phosphatase and for Golgi enzymes, fucosyl- and galactosyl-transferases. In Alzheimer-type dementia there was a selective decrease in alpha-glucosidase activity in the temporal cortex. In Huntington's disease there was a selective decrease of putamen alpha-glucosidase and fucosyl-transferase activities. It is suggested that these changes reflect highly specific alterations in glycoprotein synthesis and processing and may contribute to the underlying pathology of these disorders.

Adult↗
PubMed1985

Herpes simplex virus encephalitis. Neuroanatomical and neurochemical selectivity.

Intracerebral infection of mice with HSV-1 was found to produce a 2-3-fold increase in dopamine and serotonin metabolism in cortex, striatum, diencephalon and brain stem. Neurochemical markers of GABA and acetylcholine neurones, and neurotransmitter receptor binding sites were unchanged. The immunohistochemical distribution of virus antigen revealed high levels of immunoreactivity in s. nigra, ventral tegmental area, locus coeruleus and dorsal raphe nucleus, whilst other areas of brain stem were clear of virus antigen. The changes in monoamine metabolism observed in experimental HSV encephalitis may be related to the concentration of virus in monoamine neurones.

Acetylcholine↗
PubMed1985

Neurotransmitter metabolites, enzymes and receptors in experimental scrapie.

A comprehensive study has been made of metabolites, enzymes and receptors for a variety of neurotransmitter systems in different parts of the CNS from mice affected with 139A scrapie. Studies were made at the early clinical stage so as to minimise secondary alterations in terminally sick mice. Even though histological lesions (vacuolation) are widespread in the CNS in this model of scrapie, no consistent neurochemical changes were found in mid- or anterior brain. In the cerebellum, the activity of glutamic acid decarboxylase was reduced and the binding of [3H]muscimol to gamma-aminobutyric acid receptors was increased. In the brain stem, the concentration of 5-hydroxyindoleacetic acid (5-HIAA) was increased and there was a reduced binding of appropriate ligands to serotonin and to muscarinic cholinergic receptors. In the spinal cord, the activity of choline acetyl transferase was reduced and the concentration of 5-HIAA was increased. The extent of these alterations was about 20-40% of control values. The specificity of these changes for a few neurotransmitter systems in hind brain and spinal cord raised the possibility of their being a primary cause of clinical disease and led us to study a different scrapie model. Present and published findings show that an increased concentration of 5-HIAA, some alterations in the binding properties of serotonin receptors and a decreased number of muscarinic receptor sites are common to both 139A scrapie in CW mice and 263K scrapie in hamsters.

Animals↗
PubMed1984

Striatal dopamine receptors in Alzheimer-type dementia.

Dopamine D1 and D2 receptors were studied in putamen of post-mortem brains from controls and patients with Alzheimer-type dementia (ATD). A significant reduction in dopamine D2 receptors was observed in ATD, whereas dopamine D1 receptors were unchanged. Neurochemical markers of striatal acetylcholine and GABA-containing neurones were also within the normal range. The results are consistent with a loss of D2 receptors located on cortico-striatal neurones in putamen of some ATD patients. In contrast, markers of intrinsic neurones may remain unchanged.

Aged↗
PubMed1984

Muscarinic cholinergic receptors in a rat phaeochromocytoma cell line.

The high affinity binding of the muscarinic ligand 3H-N-methylscopolamine (3H-NMS) to intact cells of the rat pheochromocytoma cell line PC12 was studied. A single class of saturable binding sites was observed with a density of about 5000 sites per cell, and a pharmacological profile consistent with muscarinic receptors. The inhibition of 3H-NMS binding by the antagonist pirenzepine was of low affinity suggesting PC12 muscarinic receptors may be similar to those found on rat sympathetic nerve terminals.

Animals↗
PubMed1984

Studies on neurotransmitter receptor systems in neocortex and hippocampus in senile dementia of the Alzheimer-type.

Ligand binding to alpha 1-, alpha 2- and beta-adrenergic, serotonin, benzodiazepine and GABA receptors was studied in neocortex and hippocampus of controls and patients with senile dementia of the Alzheimer-type. A selective loss of serotonergic binding sites characterised as a loss of both S1 and S2 sites was observed. The reduction in serotonin receptors did not correlate with a clinical assessment of the degree of dementia, or with the extent of Alzheimer-type neuropathological change.

Aged↗
PubMed1984

Elevation of neuropeptide Y (NPY) in substantia innominata in Alzheimer's type dementia.

Concentrations of neuropeptide Y (NPY) have been determined in 12 areas of control brains and compared to those found in brains from patients with Alzheimer's type dementia (ATD). The distribution of NPY in the control brains was compared with those reported previously. Highest concentrations were identified in the subcortical structures, in particular, nucleus accumbens (203 +/- 21.7 pmol/g), amygdala (136.7 +/- 15.8 pmol/g), and substantia innominata (109.0 +/- 12.6 pmol/g). A significant elevation in NPY concentrations was identified in the region of the substantia innominata of Alzheimer brains (controls: 109.0 +/- 12.6 pmol/g, ATD: 206 +/- 28.2 pmol/g, P less than 0.001). This change in NPY concentration was similar to the increase in somatostatin concentration in this region of ATD brain. In contrast, although cortical concentrations of somatostatin were reduced in ATD, no change was found in the concentrations of NPY in the 4 regions of cerebral cortex and the remaining subcortical areas examined.

Aged↗
PubMed1984

Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides.

In patients with Alzheimer-type dementia, in addition to the well-known losses of cholinergic neurones, there is evidence of degeneration of the noradrenergic and serotonergic innervation of the cerebral cortex. While noradrenergic and cholinergic receptors are preserved there is a loss of serotonin S1 and S2 receptors, particularly in the temporal lobe. The loss of serotonin S2 receptors may occur at an early stage of the disease and, in temporal and frontal cortex, is correlated with the loss of somatostatin immunoreactivity. In patients dying in hospital with depression, and in individuals committing suicide, there are no consistent changes in monoamine metabolites. Noradrenergic, serotonergic, and other neurotransmitter receptors were found to be unchanged, although there was a moderate decrease in imipramine binding in a small group (n = 6) of subjects with a history of depression, who had committed suicide.

Aged↗
PubMed1984

Analysis of time-resolved fluorescence anisotropy decays.

We discuss the analysis of time-correlated single photon counting measurements of fluorescence anisotropy. Particular attention was paid to the statistical properties of the data. The methods used previously to analyze these experiments were examined and a new method was proposed in which parallel- and perpendicular-polarized fluorescence curves were fit simultaneously. The new method takes full advantage of the statistical properties of the measured curves; and, in some cases, it is shown to be more sensitive than other methods to systematic errors present in the data. Examples were presented using experimental and simulated data. The influence of fitting range on extracted parameters and statistical criteria for evaluating the quality of fits are also discussed.

Fluorescence Polarization↗