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R H Perry

Publications and source records attributed to R H Perry.

At least 127 records · Page 7Linked to original sources
PubMed1987

Guanine nucleotide modulation of muscarinic cholinergic receptor binding in postmortem human brain--a preliminary study in Alzheimer's disease.

The coupling of cortical muscarinic receptors to guanosine triphosphate (GTP) binding proteins, as defined by changes in agonist affinity states of the receptor in the presence of magnesium ions (Mg2+) and a GTP analogue has been investigated using carbachol in competition experiments with either N-methylscopolamine (NMS) or pirenzepine (PZ). The stability of the system with regard to autopsy delay and freezing was first established in membrane preparations from mouse brain. Applying the same methods to human autopsy tissue from the parietal cortex of Alzheimer's diseased cases and controls, matched for age and postmortem delay, there was no significant difference in the detectable coupling of the total (NMS-labelled) muscarinic receptor population. However, coupling of the 'M1' muscarinic receptor subtype, selectively labelled by PZ, appeared to be more labile than that of the receptor population as a whole and the modulation of this subtype by the GTP analogue was significantly attenuated in Alzheimer's disease.

Aged↗
PubMed1987

Sodium dependent D-[3H]aspartate binding in cerebral cortex in patients with Alzheimer's and Parkinson's diseases.

The sodium dependent binding of D-[3H]aspartate to the high-affinity glutamate uptake system was used as a marker of glutamate-releasing terminals in the cerebral cortex of brains from patients with Alzheimer-type dementia (ATD) and Parkinson's disease (PD). Sodium-dependent D-[3H]aspartate binding was reduced in the ATD patients but not in the PD patients. Within the PD patients no association was observed between sodium-dependent D-[3H]aspartate binding and the presence of dementia. In contrast choline acetyltransferase activity was reduced in both the ATD and the PD patients. The present results suggest that changes in the cortical cholinergic system can occur independently of the cortical glutamate system. The glutamatergic deficit in ATD may contribute to some of the clinical differences between the dementia of ATD and PD.

Aged↗
PubMed1987

Molecular forms of butyrylcholinesterase in the human neocortex during development and degeneration of the cortical cholinergic system.

The total levels of butyrylcholinesterase (BChE) activity and, more specifically, the distribution of BChE molecular forms were measured in the human neocortex during fetal development. Both the amount of total activity and the abundance of the different molecular forms (G1 and G4) remained relatively constant between gestational ages of 8-22 weeks and were similar to those observed in samples of cortex from aged brain. In addition, in both Alzheimer-type and parkinsonian dementia, the levels of total BChE activity as well as the relative abundance of the G1 and G4 molecular forms were similar to those observed in control tissue. Hence, both the levels of total activity and the distribution of molecular forms did not change significantly either during fetal development or in the neurodegenerative disorders of Alzheimer-type and parkinsonian dementias. Because these situations are accompanied by changes in the cortical cholinergic system (including an increase and decrease in levels of the G4 form of acetylcholinesterase, respectively), it is concluded that, at least in the human neocortex, BChE is unrelated to cholinergic neurotransmission associated with subcortical cholinergic projection fibres.

Aged↗
PubMed1987

Molecular forms of acetylcholinesterase and butyrylcholinesterase in human plasma and cerebrospinal fluid.

The measurement of cholinesterase activities in either plasma or cerebrospinal fluid (CSF) may ultimately prove to be relevant in the diagnosis of neurological and neuropsychiatric disorders. However, studies to date have examined only total enzyme activities. Therefore in the present study we have examined the distribution of the individual molecular forms of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in plasma and CSF using sucrose density gradient centrifugation. Although the total activities of AChE were of the same order of magnitude in plasma and CSF, there was a considerable difference (120-500-fold) between total BChE activity in the CSF and the BChE-rich plasma. The analysis of the individual molecular forms revealed that the predominant molecular species of AChE and BChE in the CSF--both lumbar and ventricular--was the G4 form. The G4 form also constituted the majority of the plasma BChE activity and, on average, over half (56%) of the plasma AChE activity. The significance of the AChE and BChE molecular form compositions of both plasma and CSF and their possible relationship to pathological states are discussed.

Acetylcholinesterase↗
PubMed1987

Raised thyrotrophin-releasing hormone, pyroglutamylamino peptidase, and proline endopeptidase are present in the spinal cord of wobbler mice but not in human motor neurone disease.

The Wobbler mouse (wr) is a mutant that exhibits loss of anterior horn cells in the spinal cord and brainstem and subsequent muscle wasting, particularly of the forelimbs and neck. The wr mice, 2-3 months of age, were found to have increased levels of immunoreactive-thyrotrophin-releasing hormone (ir-TRH) in the spinal cord and pons and medulla, but not in other CNS areas. This increase was observed in dorsal and ventral cord and at cervical, thoracic, and lumbar levels and was confirmed by HPLC to be authentic TRH. The levels of immunoreactive-somatostatin, -neurotensin, and -substance P were not raised in the CNS of wr mice. The activities of two peptidases capable of degrading TRH, pyroglutamylaminopeptidase (PGAP, EC 3.4.11.8) and proline endopeptidase (PEP, EC 3.4.21.26), and the level of 5-hydroxyindoleacetic acid were also raised in the spinal cord of 2-3-month-old wr mice although the activities of alanine aminopeptidase and lactate dehydrogenase and the level of 5-hydroxytryptamine were not. Increased spinal cord levels of ir-TRH and PGAP and PEP activities were not observed in the 1-month-old wr mice. In addition, a pilot study using spinal cord obtained at autopsy from three patients with motor neurone disease and 12 control subjects indicated no increase in spinal cord ir-TRH, PGAP, or PEP in human motor neurone disease.

Aminopeptidases↗
PubMed1987

Nicotinic receptor abnormalities in Alzheimer's and Parkinson's diseases.

The status of cholinergic receptors in dementia is related to the question of potential cholinergic therapy. Whilst muscarinic receptor binding is generally reported to be normal or near normal, findings are reported which indicate substantial reductions of hippocampal nicotinic (high affinity nicotine) binding (occurring in conjunction with decreased choline acetyltransferase) in both Alzheimer's and Parkinson's but not Huntington's disease. A further indication that nicotinic receptor function may be abnormal in Alzheimer's disease is the extensive loss of an endogenous compound, detected for the first time in human brain, which inhibits normal nicotinic binding. Both receptor binding and the inhibitor are also substantially decreased with increasing age in the normal hippocampus.

Adult↗
PubMed1987

Cortical neuropathological and neurochemical substrates of Alzheimer's and Parkinson's diseases.

Whilst the neuropathological correlates of Alzheimer type dementia--cortical neurofibrillary tangles and senile plaques--are well defined, the prevalence of these cortical abnormalities in Parkinson's disease and their relation to dementia is unclear. In a series of 46 consecutive cases of clinically and pathologically established Parkinson's disease the prevalence of mild Alzheimer-type pathology (exceeding the normal but not as extensive as in Alzheimer's disease) was increased 2 to 3 fold compared with an age-matched control group, although there was no obvious relation to the presence or severity of dementia. In a subgroup of Parkinsonian cases (both demented and non-demented), examined neurochemically, there were both similarities (decreased choline acetyltransferase, nicotinic and serotonergic S 1 receptor activities) and distinctions (increased muscarinic receptor binding--particularly to the "L" subtype, and normal serotonergic S 2, somatostatin, and D-aspartate binding together with normal levels of an endogenous nicotine binding inhibitor) compared with a group of cases with Alzheimer's disease. Amongst the various pathological and chemical indices examined, only presynaptic cholinergic markers (including the number of Meynert neurons) and S 1 receptor binding were related to dementia in Parkinson's disease. It is suggested that whilst coincidental classical Alzheimer's disease is infrequent in Parkinson's disease (5% in the present series) Alzheimer's disease itself is distinguished from Parkinson's disease by the formation of numerous neocortical neurofibrillary tangles and a reduction in glutamate uptake, serotonergic S 2 receptors and possibly in endogenous nicotine binding inhibitor.

Adult↗
PubMed1986

Aluminosilicates and senile plaque formation in Alzheimer's disease.

Aluminium and silicon were found to be colocalised in the central region of senile plaque cores in studies with energy dispersive X-ray microanalysis. The distribution of these elements was similar in cores isolated from the cerebral cortex of patients with senile dementia of the Alzheimer type and in cores studied in situ from tissue sections from the cerebral cortex of presenile and senile patients with Alzheimer's disease, and elderly, mentally normal patients. High-resolution solid-state nuclear magnetic resonance techniques showed aluminium and silicon to be present as aluminosilicates. The presence of aluminosilicates at the centre of senile plaque cores contrasts with the distribution of other inorganic constituents and suggests that they may be involved in the initiation or early stages of senile plaque formation.

Aged↗
PubMed1986

Aluminosilicates and the ageing brain: implications for the pathogenesis of Alzheimer's disease.

Senile plaques are a neuropathological feature of the ageing brain and consist of abnormal neuritic and glial processes surrounding an extracellular core of material with fibrillary ultrastructure. Present at low densities in the cerebral cortex of most aged individuals, they occur in large numbers in Alzheimer's disease, the major form of senile dementia. Energy-dispersive X-ray microprobe analysis of isolated cores and plaques in situ from patients with Alzheimer's disease or Down's syndrome and from normal controls has shown co-localization of high concentrations of aluminium (4-19%) and silicon (6-24%) at the centre of the core. The presence of these elements as aluminosilicates has been confirmed using solid-state 27Al nuclear magnetic resonance. These findings provide a link with the other major neuropathological feature of Alzheimer's disease, the neurofibrillary tangle-bearing neurons, where high intracellular levels of Al and Si have also been reported. The focal deposition of these elements may be an early and essential factor in the pathogenesis of Alzheimer-type changes, reflecting an increased exposure to aluminium.

Aged↗
PubMed1986

Recovery and measurement of specific RNA species from postmortem brain tissue: a general reduction in Alzheimer's disease detected by molecular hybridization.

The recovery of RNA from postmortem (PM) brain tissues was quantified by molecular hybridization. RNA degradation rates postmortem were faster in mice with herpes encephalitis than with uninfected mice, but clear ribosomal peaks could be seen up to 72 hr after death. In a comparison between frontal cortex samples from neurologically normal and Alzheimer's disease cases a reduction in ribosomal, poly A, preproenkephalin, and preprosomatostatin RNA levels was observed in the Alzheimer's disease group. This general reduction may be influenced by the cause of death as well as the pathology.

Alzheimer Disease↗
PubMed1986

Solitary extranodal lymphoma of sciatic nerve.

A solitary extranodal malignant lymphoma (non-Hodgkin's lymphoma, centrocytic type) of the sciatic nerve is described in a 64-year-old woman. Whereas previous reports of peripheral nervous system lymphoma have described multifocal lesions and generally an association with systemic lymphomas, in this case the lymphoma was confined to a segment of a peripheral nerve and was not associated with systemic lymphoma. The clinical presentation was a progressive weakness and sensory disturbance in the right leg. Clinical and electrophysiological examination indicated a lesion in the sciatic nerve, and computerised tomography of the right thigh revealed an enlarged distal segment of the sciatic nerve. On surgical exploration, a fusiform tumour of the sciatic nerve was resected. Pathological examination, including immunohistology and electron microscopy revealed a malignant lymphoma. An unusual histological feature was the presence in the tumour and infiltrated nerve of an extracellular eosinophilic non-amyloid material, similar to that occasionally seen in nodal lymphomas. The patient showed no evidence of lymphoma at other sites at the presentation and this has been confirmed at a 9-month review.

Female↗
PubMed1986

Cholinergic receptors in cognitive disorders.

Cholinergic receptors (muscarinic subtypes M1 and M2, and putative nicotinic binding) have been examined in the hippocampus obtained at autopsy from a variety of patients with cognitive disorders (Alzheimer's, Parkinson's, and Huntington's diseases, Down's Syndrome and alcoholic dementia) and compared with neurologically normal controls and cases of Motor Neuron disease. In all of the disorders associated with a pre-synaptic cortical cholinergic deficit reflected by an extensive loss of choline acetyltransferase (Alzheimer's disease, Parkinson's disease and Down's Syndrome) there was a substantial reduction in the binding of (3H) nicotine to the nicotinic receptor. By contrast reductions in both muscarinic subtypes (M1 and M2) were apparent to only a moderate extent in Alzheimer's disease, whereas in Parkinson's disease binding was significantly increased (apparently not in relation to anti-cholinergic drug treatment) in the non-demented but not demented cases. A further abnormality detected in Alzheimer's disease but not the other disorders investigated was a decrease in an endogenous inhibitor of nicotinic binding, the identity of which is as yet unknown but which may be a candidate for a possible endogenous modulator of the nicotinic receptor. These observations suggest that in Alzheimer's disease not only muscarinic but also nicotinic receptor function should be considered in relation both to future therapeutic strategies and, in the search for a clinical marker which might be of diagnostic value, to potential probes of the cortical cholinergic system.

Cognition Disorders↗
PubMed1986

Neocortical cholinergic enzyme and receptor activities in the human fetal brain.

In the human fetus, obtained postmortem at estimated gestational ages of 8-22 weeks, biochemical activities of cortical choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were comparable to those of adult brain tissue. In contrast cholinergic receptor binding, including muscarinic M1 and M2 subtypes (measured by displacement of [3H]N-methylscopolamine with, respectively, pirenzepine and carbachol) and [3H]nicotine (putative nicotinic) binding were undetectable before 13-14 weeks and even at 22 weeks were substantially (three- to fourfold) below the respective adult values. Cortical ChAT activity decreased significantly with gestational age whereas binding to the three receptors, including the proportion M1/M2, increased significantly. AChE was present at all ages investigated as the two molecular monomeric (G1) and tetrameric (G4) forms. The proportion of G4, which was much more soluble in fetal compared with adult cortex, increased approximately threefold. Histochemically AChE, although intense in the nucleus of Meynert, was generally confined to subcortical white matter at early fetal developmental periods, appearing later in the cortex localized to nerve fibres and occasional cell bodies. These observations suggest that during the second trimester of human fetal development, cortical cholinergic function may be preceded by relatively high ChAT activity and paralleled not only by increasing receptor binding but also by a proportional increase in the tetrameric form and histochemical reactivity of AChE.

Acetylcholinesterase↗
PubMed1986

Molecular forms of acetylcholinesterase and butyrylcholinesterase in the aged human central nervous system.

The distribution of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) molecular forms and their solubility characteristics were examined, using density gradient centrifugation, in various regions of the postmortem human CNS. Total AChE activity varied extensively (50-fold) among the regions investigated, being highest in the telencephalic subcortical structures (caudate nucleus and nucleus of Meynert); intermediate in the substantia nigra, cerebellum, and spinal cord; and least in the fornix and cortical regions (hippocampus and temporal and parietal cortex). Total BChE activity was, in contrast, much more evenly distributed, with only a threefold variation between the regions studied. Although the patterns of molecular forms of each enzyme were broadly similar among the different areas, regional variations in the distribution and abundance of the various forms of AChE were much greater than those of BChE. Thus, although the tetrameric G4 form of AChE constituted the majority of the total AChE activity in all regions examined, the ratio of the G4 form to the monomeric G1 form, the latter of which constituted the majority of the remaining activity, varied markedly, ranging from 21 in the caudate nucleus to 1.7 in the temporal cortex. In addition to the G4 and G1 forms of AChE, the dimeric G2 form was observed in the nucleus of Meynert and a fast-sedimenting (16S) species was found in samples of both the parietal cortex and spinal cord. In contrast, the G4 and G1 forms of BChE were the only molecular species observed in the different areas and the G4:G1 ratio varied from 3.3 in the substantia nigra to 0.9 in the temporal cortex. Regarding the solubility characteristics of the individual AChE and BChE molecular forms, the majority of the G4 form of AChE was extractable only in the presence of detergent, indicating a predominantly membrane-bound localization of this species. The smaller AChE forms (G1 and G2) and both the G1 and G4 forms of BChE were all relatively evenly distributed between soluble and membrane-bound species. These findings are discussed in relation to neurochemical and neuroanatomical, particularly cholinergic, features of the regions examined.

Acetylcholinesterase↗