Selective vulnerability of neurones in organic dementia

Spillane, J. A.; White, Pamela; Goodhardt, Michèle; Flack, R. H. A.; Bowen, David M.; Davison, Alan

doi:10.1038/266558a0

Cited by 102 publications

(24 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data, taken together with the aging-related changes in enzyme activities and ACh levels reported above, strongly suggest that the effect of aging on peripheral cholinergic neu rons is not generalized, but is specifically directed toward the neuronal periphery. This view is in contrast with several studies in the CNS, in which age-related changes in enzyme activities have been interpreted as largely de pendent on damage to or a loss of cholinergic cell bodies [8,9,23,34,39].…”

Section: Relation Between Enzyme Activities and Ach Levelscontrasting

confidence: 48%

Development and Aging of Cholinergic Synapses

Marchi¹,

Dw²,

Giacobini³

et al. 1980

Dev Neurosci

View full text Add to dashboard Cite

Age-related changes in the activities of choline acetyltransferase and acetylcholinesterase in avian sympathetic ganglia, ciliary ganglia and iris have been determined throughout the posthatching life span. Kinetic characteristics of these enzymes have been analyzed in the nerve terminals in the iris from early embryonic stages to the latest periods of life. Enzyme activities and kinetics have been related to each other and also to the endogenous levels of acetylcholine. The regulation of the biosynthetic mechanism for acetylcholine through choline uptake and choline acetyltransferase activity in the developing nerve terminal have been examined. The activities of both enzymes in all tissues are reduced at later ages, which is referred to declines in V_max, as the K_m values do not vary significantly at any age. Declines with age are most pronounced in the iris, both in choline acetyltransferase activity and V_max and in acetylcholine levels, supporting our view of the peripheral autonomic nerve terminal as a major locus for the effects of aging on the peripheral nervous system.

show abstract

Section: Relation Between Enzyme Activities and Ach Levelscontrasting

confidence: 48%

Development and Aging of Cholinergic Synapses

Marchi¹,

Dw²,

Giacobini³

et al. 1980

Dev Neurosci

View full text Add to dashboard Cite

show abstract

“…Electrophysiologic studies in monkeys indicate that the activity of a high percentage of the basal nucleus neurons is modulated by some aspects of food reward after successful completion of a motor task (52). The ascending cholinergic projection to neocortex is also of potential clinical pharmacological and neuropathologic importance because blocking cholinergic neurotransmission with muscarinic receptor antagonists impairs human memory functions (53) and presenile "cortical" dementia (Alzheimer disease) is associated with marked reduction in cholinergic neurochemical markers in neocortex (54). The delineation of a major subcortical contribution to the cortical cholinergic innervation suggests that studies directed at understanding of the pathogenesis of such clinical disorders might profitably be diNeurobiology: Johnston et al 5896 Neurobiology: Johnston et al…”

Section: Methodsmentioning

confidence: 99%

Evidence for a cholinergic projection to neocortex from neurons in basal forebrain.

Johnston

McKinney

Coyle

1979

Proc. Natl. Acad. Sci. U.S.A.

326

112

View full text Add to dashboard Cite

Unilateral stereotaxic injection of 3.5 nmol of kainic acid into the ventral globus pallidus of rats reduced biochemical cholinergic neuronal markers by 45-50% and virtually eliminated histochemical staining for acetylcholinesterase in neocortex ipsilateral to the lesion. At the lesion site, the large, multipolar neurons that stain densely for acetylcholinesterase were absent when compared with the uninjected side. Kainate was as effective as electrocoagulation for reducing cholinergic markers although it did not affect aminergic projections ascending through the lesioned area. The conclusion that the cholinergic projection originated in neuronal perikarya at the lesion site was supported by the failure of kainate or electrolytic lesions in contiguous regions to produce similar effects. These studies provide strong evidence for a cholinergic projection to neocortex from neurons in the forebrain in the nucleus basalis.The mammalian cerebral cortex contains the neurotransmitter acetylcholine (AcCho) and moderately high levels of activity of its biosynthetic enzyme choline acetyltransferase (acetylCoA:choline O-acetyltransferase; EC 2.3.1.6) and its catabolic enzyme acetylcholinesterase (AcCho-esterase; acetylcholine acetylhydrolase; EC 3.1.1.7) (1, 2). AcCho and drugs that alter cholinergic neurotransmission influence cortical electrical activity, and under physiologic conditions AcCho is released from the surface of the neocortex (3). Neocortical neurons, especially in the deeper layers, are strongly excited by the iontophoretic application of AcCho (4); and muscarinic cholinergic receptors have been characterized in neocortex by neurophysiologic and neurochemical methods (5-7). Ligand binding studies with a-bungarotoxin have also demonstrated the presence of nicotinic receptors in cortex (8, 9). These findings suggest that the neocortex receives a substantial cholinergic innervation.Previous studies on the possible source of cortical cholinergic innervation have, however, been inconclusive. Undercutting of the cerebral cortex to lesion cortical afferents results in a marked reduction in the activity of choline acetyltransferase, suggesting a subcortical source of cholinergic innervation (10); however, interpretation of the effects of this local lesion is confounded by the possible direct or retrograde damage to cortical intrinsic cholinergic neurons. Shute and Lewis, in a series of elegant experiments, used histochemical techniques to stain for AcCho-esterase activity in neuronal fibers and concluded that the neocortical cholinergic innervation arose from perikarya situated in the brain stem and diencephalon (11); however, the recent demonstration that many noncholinergic neurons are also cholinesterase-positive has undermined the specificity of their technique (12-14). In contrast, McGeer et al. (15), utilizing antiserum against choline acetyltransferase to stain for neurons containing this enzyme, which presumably are cholinergic, reported that choline acetyltransferase was confined to cortical intrins...

show abstract

“…The growing evidence of abnormalities in various components of the cholinergic transmitter system in Alzheimer's disease (Davis & Maloney, 1976;Perry et al 1977;Spillane et al 1977;White et al 1977) may also be partly related to or reflected by plaque formation. Thus a significant decline in cholineacetyl-transferase occurs with increasing plaque numbers in the neocortex of non-demented and demented old people (Perry et al 1978); Perry & Perry (1980) also showed significant correlations between plaque numbers and decreasing acetylcholinesterase.…”

mentioning

confidence: 99%

Plaques, tangles and Alzheimer's disease

Tomlinson¹

1982

Psychol. Med.

View full text Add to dashboard Cite

Selective vulnerability of neurones in organic dementia

Cited by 102 publications

References 16 publications

Development and Aging of Cholinergic Synapses

Development and Aging of Cholinergic Synapses

Evidence for a cholinergic projection to neocortex from neurons in basal forebrain.

Plaques, tangles and Alzheimer's disease

Contact Info

Product

Resources

About