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M C Royston

Publications and source records attributed to M C Royston.

42 records · Page 3Linked to original sources
PubMed1989

Reduced D-[3H]aspartate binding in Down's syndrome brains.

The binding of D-[3H]aspartate to glutamate uptake sites was measured in post-mortem brains from subjects with Down's syndrome (DS) and age-matched controls. DS brains had substantially reduced D-[3H]aspartate binding in the frontal and temporal cortex, hippocampus and caudate nucleus. There was no correlation between the numbers of Alzheimer-like plaques and tangles or clinically-assessed dementia and D-[3H]aspartate binding in DS brains. The binding of [3H]N-(1-[2-thienyl]cyclohexyl)piperidine ([3H]TCP) to postsynaptic N-methyl-D-aspartate sites was normal in DS brains. This study suggests that the reduction in glutamate uptake sites in DS is more substantial and widespread than in Alzheimer's disease.

Aged↗
PubMed1989

Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia.

Glutamatergic mechanisms have been investigated in postmortem brain samples from schizophrenics and controls. D-[3H]Aspartate binding to glutamate uptake sites was used as a marker for glutamatergic neurones, and [3H]kainate binding for a subclass of postsynaptic glutamate receptors. There were highly significant increases in the binding of both ligands to membranes from orbital frontal cortex on both the left and right sides of schizophrenic brains. The changes are unlikely to be due to antemortem neuroleptic drug treatment, because no similar changes were recorded in other areas. A predicted left-sided reduction in D-[3H]aspartate binding was refuted at 5% probability, but not at 10%. Previously reported high concentrations of dopamine in left amygdala were strongly associated with low concentrations of D-[3H]aspartate binding in left polar temporal cortex in the schizophrenics. The findings are compatible with an overabundant glutamatergic innervation of orbital frontal cortex in schizophrenia. The results also suggest that schizophrenia may involve left-sided abnormalities in the relationship between temporal glutamatergic and dopaminergic projections to amygdala.

Aspartic Acid↗
PubMed1988

Regional changes in [3H]D-aspartate and [3H]TCP binding sites in Alzheimer's disease brains.

The specific binding of [3H]D-aspartate, a marker for the presynaptic glutamate uptake site, and [3H]N-(1-[2-Thienyl]cyclohexyl)-piperidine [( 3H]TCP), a high affinity ligand for the N-methyl-D-aspartate (NMDA)-associated phencyclidine binding site, was measured in homogenates of brain from normal subjects and from subjects with neuropathologically confirmed Alzheimer's disease. Alzheimer's disease was associated with a reduction in [3H]D-aspartate binding density in temporal cortex and caudate nucleus. By contrast, a reduction in the receptor density for [3H]TCP binding was only recorded in the frontal cortex. Thus, glutamate-containing nerve terminals are severely reduced in Alzheimer's disease, whilst the postsynaptic NMDA-phencyclidine receptor complex is much less affected. These findings have implications for theories of glutamate neurotoxicity in Alzheimer's disease.

Aged↗
PubMedDate not supplied

Life-long overexpression of S100beta in Down's syndrome: implications for Alzheimer pathogenesis.

Chronic overexpression of the neurite growth-promoting factor S100beta has been implicated in the pathogenesis of neuritic plaques in Alzheimer's disease. Such plaques are virtually universal in middle-aged Down's syndrome, making Down's a natural model of Alzheimer's disease. We determined numbers of astrocytes overexpressing S100beta, and of neurons overexpressing beta-amyloid precursor protein (beta-APP), and assayed for neurofibrillary tangles in neocortex of 20 Down's syndrome patients (17 weeks gestation to 68 years). Compared to controls, there were twice as many S100beta-immunoreactive (S100beta+) astrocytes in Down's patients at all ages: fetal, young, and adult (p = 0.01, or better, in each age group). These were activated (i.e., enlarged), and intensely immunoreactive, even in the fetal group. There were no neurofibrillary changes in fetal or young Down's patients. The numbers of S100beta+ astrocytes in young and adult Down's patients correlated with the numbers of neurons overexpressing beta-APP (p < 0.05). Our findings are consistent with the idea that conditions--including Down's syndrome--that promote chronic overexpression of S100beta may confer increased risk for later development of Alzheimer's disease.

Adult↗