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Biomedical subjects

J M Candy

Publications and source records attributed to J M Candy.

At least 91 records · Page 5Linked to original sources
PubMed1983

Pathological changes in the nucleus of Meynert in Alzheimer's and Parkinson's diseases.

Combined neuropathological and neurochemical assessment of the nucleus of Meynert in senile dementia of Alzheimer type (SDAT) have demonstrated that the cholinergic biochemical activity, choline acetyltransferase, is more extensively reduced in the nucleus (over 90%) than the loss of putative cholinergic perikarya (35%). Acetylcholinesterase histochemical activity was however substantially retained in individual neurones in the nucleus although virtually absent from the neocortex in SDAT. These abnormalities are consistent with a primary degeneration of cholinergic axons projecting to the cortex and secondary loss of perikarya from the subcortical nucleus. In contrast, preliminary observations on cases of Parkinson's disease suggest that the neuronal loss from the nucleus of Meynert may be greater in this disease than in SDAT, and previous studies have not consistently demonstrated a reduction in cortical choline acetyltransferase activities in Parkinson's disease. These observations, together with major differences in the neuropathology of the nucleus in SDAT and Parkinson's disease (neurofibrillary tangle and Lewy body formation, respectively) suggest that the involvement of the cholinergic system may differ in the two disease processes.

Acetylcholinesterase↗
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↗
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↗
PubMed1979

Interactions of (+)-amphetamine and chlorpromazine on neurones in the lower brain stem of the rat.

1 The ability of chlorpromazine to antagonize the effects of iontophoretic application of (+)-amphetamine to single neurones in the medulla and lower pons of anaesthetized rats has been studied. 2 Chlorpromazine, administered systemically or iontophoretically, consistently and specifically antagonized the excitatory actions of (+)-amphetamine, but not those of noradrenaline on the same neurone. 3 It is concluded that chlorpromazine reduces the effect of (+)-amphetamine by a presynaptic mechanism. 4 (+)-Amphetamine did not mimic the prolonged inhibitory response of some neurones to noradrenaline but often excited these neurones and chlorpromazine blocked these excitatory responses to (+)-amphetamine.

Acetylcholine↗
PubMed1977

A presynaptic site of action within the mesencephalic reticular formation for (+)-amphetamine-induced electrocortical desynchronization.

1. Changes induced in the electrocorticogram by the bilateral perfusion of (+)-amphetamine into the mesencephalic reticular formation (MRF) have been studied in cat encéphale isolé preparations. 2. (+)-Amphetamine, applied for 5 min in the MRF, mimicked the electrocortical desynchronization induced by the perfusion of (-)-noradrenaline (NA) or (-)-alpha-methylnoradrenaline (AMNA) into the same sites. 3. Perfusion of 6-hydroxydopamine (6-OHDA) also induced desynchronization but, over the 1 h perfusion period, slow wave activity gradually returned to the electrical record. 4. Following the application of 6-OHDA the effect of (+)-amphetamine was abolished or significantly attenuated, whereas the effect of NA or AMNA was not affected. 5. The electrocortical desynchronization induced by (+)-amphetamine could be restored if its application was preceded by perfusion with NA or AMNA. 6. Fluorescence studies using AMNA indicated that 6-OHDA depleted noradrenergic nerve terminals near the cannulae tips. However, the terminals were still capable of taking up exogenously applied AMNA. 7. These results suggest that (+)-amphetamine has a presynaptic action on noradrenergic nerve terminals within the MRF.

Animals↗
PubMed1976

The role of endogenous catecholamines in the regulation of electrocortical activity in the encephale isole cat.

Experiments were performed on encephale isole cats. The cats were either untreated or pretreated with reserpine, alpha-methyl-p-tyrosine (AMPT) or FLA 63, and the depletion of endogenous noradrenaline was determined by fluorescence microscopy. Pretreatment with reserpine reduced waking and spindle sleep while the synthesis inhibitors did not. A combined pretreatment with reserpine and AMPT or FLA 63 was necessary to deplete totally brain stem noradrenaline. Under these circumstances, behavioural arousal was abolished and all electrocortical activity except spindling was also abolished. Injection of L-DOPA into cats pretreated with reserpine and AMPT produced behavioural alerting and low voltage, high frequency electrocortical activity. In cats pretreated with reserpine and FLA 63, the minimum effective dose of L-DOPA was often elevated, and when the low voltage, high frequency activity occurred, it was accompanied by spindling. It was accompanied by spindling. It is suggested that dopamine and noradrenaline independently modulate electrocortical activity, dopamine mediating spindling, and noradrenaline inhibiting spindling but mediating low voltage, high frequency activity.

Animals↗