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R H Perry

Publications and source records attributed to R H Perry.

At least 181 records · Page 10Linked to original sources
PubMed1983

Post mortem levels of thyrotropin-releasing hormone and neurotensin in the amygdala in Alzheimer's disease, schizophrenia and depression.

The levels of neurotensin and thyrotropin-releasing hormone (TRH) in normal post mortem human amygdala have been compared with those in cases of schizophrenia, Alzheimer's disease and depression. Amongst various factors which can influence post mortem human brain biochemistry (including age, sex, post mortem delay, time of death, disease status and severity), sex difference appeared to be responsible for the most extensive variation. The levels of both peptides were nearly doubled in males compared with females and this increase was significant in the case of neurotensin. There was also a positive correlation between neurotensin and TRH levels. Although levels of neurotensin and TRH tended to be lower in the disease groups these trends did not reach significance.

Aged↗
PubMed1983

Metabolically active synaptosomes can be prepared from frozen rat and human brain.

Nerve ending particles (synaptosomes) were prepared from pieces of rat and human brain and from brain homogenate that had been frozen and thawed under a variety of conditions. Their purity, as judged by electron microscopy, and performance in terms of a number of metabolic and functional parameters [accumulation of tissue potassium, respiration, release of transmitter amino acids, and the responses on these indices to depolarisation by veratrine (VX)] were compared with those of fresh tissue-derived synaptosomes. It was found that rapid freezing and/or slow thawing severely impaired the subsequent performance of incubated synaptosomes. In contrast, synaptosomes from tissue frozen slowly and thawed rapidly showed relatively good retention of morphology and metabolic performance. It was better to use whole (1-5 g) pieces of tissue than tissue homogenate: the synaptosome fraction from frozen tissue pieces contained 80% of the proportion of identified synaptosomes found in the fresh tissue synaptosome fraction, its respiratory rate was 65%, and its tissue potassium content 70% of that of fresh controls. Moreover, it responded to VX or potassium stimulation by showing increased respiratory rate, decreased tissue potassium, and increased release of neurotransmitter amino acids, to an extent that was comparable to that of fresh tissue fractions. Thus, preparations from frozen rat and human brain were shown to be metabolically and functionally active, and can be used for a variety of neurotransmitter-related studies.

Animals↗
PubMed1983

Decreased imipramine binding in the brains of patients with depressive illness.

The binding of tritiated imipramine was significantly reduced in the hippocampus and occipital cortex from a series of patients with depressive illness compared with age-matched patients with no psychiatric disorder. In contrast there was no change in imipramine binding in established cases of senile dementia of Alzheimer-type. Scatchard analysis indicated normal binding affinity but a reduction in the number of imipramine binding sites in depression. These observations parallel previous findings of decreased binding sites in platelets from depressed patients and suggest there may be an abnormality in the uptake mechanism for serotonin in depression.

Aged↗
PubMed1982

Extensive loss of choline acetyltransferase activity is not reflected by neuronal loss in the nucleus of Meynert in Alzheimer's disease.

Choline acetyltransferase activity in discrete tissue punches from the nucleus of Meynert and in tissue from the temporal cortex was reduced by at least 90% and 75%, respectively, in 5 out of 6 elderly cases of Alzheimer's disease compared with 5 normal cases. In contrast, estimates of neurone density in these same cases revealed that there was only, on average, a 33% neurone loss in the nucleus of Meynert in Alzheimer's disease. These observations suggest that a key pathological change in Alzheimer's disease may be the 'down regulation' of transmitter-specific enzyme production in cholinergic neurones, and that neurone loss itself may be a secondary feature of the disease.

Aged↗
PubMed1982

Use of post-mortem human synaptosomes for studies of metabolism and transmitter amino acid release.

Synaptosomes have been prepared from human brain obtained at autopsies carried out up to 24 h postmortem (p.m.). They showed generally good retention of morphology, as well as accumulation of tissue potassium and linear rates of oxygen uptake. In response to veratrine depolarization they showed increased respiration rate, decreased tissue potassium content and the specific release of transmitter amino acids. Regression analysis indicated that metabolically and functionally active preparations may be obtained up to ca. 25 h p.m. Preparations obtained from patients dying with brain injury were inactive.

Adult↗
PubMed1982

The influence of agonal status on some neurochemical activities of postmortem human brain tissue.

The number of general biochemical and specific neurochemical activities have been investigated in postmortem human brain tissue in relation to the terminal state of the patient. Cases were broadly divided into those dying after a period of normal or near normal health (Category A) and those dying after a prolonged period of severe illness (Category B). Whilst most of the metabolic and transmitter-related enzymes, amino acids and neuropeptides investigated were not significantly different between the two groups, there were in Category B highly significant reductions in glutamate decarboxylase, phosphofructokinase and tissue pH, and increases in several amino acids including, most extensively, tryptophan. The possible use of such activities as 'markers' of agonal status in the selection of normal material and in the matching of control and pathological material in postmortem human brain studies is discussed.

Amino Acids↗
PubMed1981

Properties and possible significance of substance P and insulin fibrils.

The neuropeptide substance P forms polymeric fibrils similar to those previously reported for the hormone, insulin. Structural and chemical aspects of these two fibrillary forms have been compared and their possible existence in vivo considered. Numerous substance P fibrils are readily formed in vitro in mM solutions under conditions which are physiological with respect to salt concentration, pH and temperature, whereas more severe conditions (heat and acid) are apparently required for the rapid formation of numerous insulin fibrils. Morphologically, both fibrils appear to be relatively long and unbranched and the neuropeptide fibrils are similar in size to such naturally occurring structures as neurofilaments. Disaggregation of the neuropeptide fibril follows dilution (1000-fold) whilst more stringent (alkaline) treatment is apparently necessary for insulin fibril dissociation. These observations are discussed in relation to the role of an insulin-like peptide in the formation of certain types of amyloid and the possibility that fibrillary of similar polymeric forms of substance P may exist in normal tissue.

Insulin↗
PubMed1981

Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease.

The activity of the noradrenergic marker enzyme dopamine-beta-hydroxylase was measured in brains removed postmortem from control patients and patients with Alzheimer's disease. Enzyme activity was decreased in the frontal and temporal cortices and hippocampus in patients with Alzheimer's disease, but was within the normal range in patients with depression, multiinfarct dementia, and terminal coma.The decrease in enzyme activity in Alzheimer's disease may reflect an abnormality of cortical noradrenergic fibres in some patients with the disease.

Aged↗
PubMed1981

Neuropathological and biochemical observations on the noradrenergic system in Alzheimer's disease.

Abnormalities of the noradrenergic system in Alzheimer's disease have been investigated by comparing quantitative histological and biochemical components of this transmitter system (locus coeruleus neuron counts and cortical dopamine beta-hydroxylase (DBH) activity, respectively) in a series of demented and non-demented cases. Cortical activities of the noradrenergic enzyme, DBH, did not correlate significantly with the number of locus coeruleus neurons, a finding which contrasts with the previous observations in animal brains of reductions in cortical DBH following locus coeruleus lesions. The extent of Alzheimer-type abnormalities, assessed from either morphological measures (mean plaque counts) or clinical measures (Mental Test Scores) of severity, was not significantly related to the cortical activity of DBH in the present series of cases, although non-significant trends were apparent. In contrast the activity of the cholinergic enzyme choline acetyltransferase did, as previously reported, correlate significantly with the extent of Alzheimer-type abnormalities, suggesting that abnormalities of the cholinergic system are more closely associated with specific aspects of the Alzheimer disease process than those of the noradrenergic system.

Alzheimer Disease↗
PubMed1981

Neuropeptides in Alzheimer's disease, depression and schizophrenia. A post mortem analysis of vasoactive intestinal peptide and cholecystokinin in cerebral cortex.

Vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) have been measured, by radioimmunoassay, in cerebral cortex obtained at autopsy from patients without neurological or psychiatric disease and from patients with Alzheimer's disease, depression and schizophrenia. Sephadex gel filtration indicated that over 90% of the CCK immunoreactivity was associated with the octapeptide in extracted material from the different clinical groups investigated. There were no significant differences from the normal in the overall concentrations of either VIP or CCK in any of the psychiatric groups examined, although differences in Alzheimer's disease were apparent when cases were grouped according to postmortem delay.

Alzheimer Disease↗
PubMed1981

Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes.

Activities relating to 3 neurotransmitter and 4 neuropeptide systems have been examined in human temporal lobe (post mortem) for their relationships with age and Alzheimer-type changes (senile plaques and cognitive function). Significant alterations with increasing age (from 61 to 92 years) in a series of non-demented cases included a reduction of the cholinergic enzyme, choline acetyltransferase, and an increase in vasoactive intestinal peptide immunoreactivity. In cases of alzheimer's disease the only neurochemical activity investigated which correlated significantly with cognitive impairment (assessed from a Mental Test Score obtained shortly before death) and with the severity of Alzheimer-type abnormalities (senile plaques density) was choline acetyltransferase. Further analyses of the data in relation to the severity of plaque formation suggest that alterations in other neurochemical activities including reductions in dopamine-beta-hydroxylase activity, cholecystokinin octapeptide (aqueous extracted) and somatostatin immunoreactivities and an increase in substance P immunoreactivity, may occur at later stages of the disease process. These comparative data suggest that biochemical changes in this brain area associated with age and earlier stages of Alzheimer's disease may be relatively selective.

Aged↗
PubMed1980

Coenzyme A-acetylating enzymes in Alzheimer's disease: possible cholinergic 'compartment' of pyruvate dehydrogenase.

In the mammalian central cholinergic system the precise mechanism for the production of acetyl-CoA used in acetylcholine synthesis has not yet been identified. As a possible means of investigating this problem the relationship between the activities of several enzymes which can synthesize acetyl-CoA and the cholinergic defect of Alzheimer's disease has been examined. Small, but significant reductions in the activities of pyruvate dehydrogenase, ATP-citrate lyase and acetoacetyl-CoA thiolase were found in post mortem brain tissue from cases of Alzheimer's disease, and the decrease in pyruvate dehydrogenase appeared to be related to the extent of the cholinergic defect (as indicated by loss of choline acetyltransferase). Furthermore, the regional distribution of choline acetyltransferase was similar to that of pyruvate dehydrogenase but not to the distribution of the other enzymes investigated in normal human brain tissue. These observations tend to support a recent suggestion that there may be a particular form of pyruvate dehydrogenase associated with cholinergic neurones.

ATP Citrate (pro-S)-Lyase↗
PubMed1980

Histochemical observations on cholinesterase activities in the brains of elderly normal and demented (Alzheimer-type) patients.

The extent and distribution of acetylcholinesterase staining in the hippocampus has been compared in normal elderly cases and patients with Alzheimer's disease. In both groups some senile plaques and neurofibrillary tangles stain positively with acetylcholinesterase and in Alzheimer's disease there is a reduction in acetylcholinesterase staining of nerve processes. The positive staining of processes in senile plaques suggests that they are, at least partly, derived from cholinergic, axonal fibres and the decrease in acetylcholinesterase staining of nerve processes may indicate a diminution in cholinergic, afferent input fibres to the hippocampus in Alzheimer's disease.

Acetylcholinesterase↗