Journal ArticleDOI
Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor.
Walter Fischer,Klas Wictorin,Anders Björklund,Lawrence R. Williams,Silvio Varon,Fred H. Gage +5 more
TLDR
Continuous intracerebral infusion of NGF over a period of four weeks can partly reverse the cholinergic cell body atrophy and improve retention of a spatial memory task in behaviourally impaired aged rats.Abstract:
In aged rodents, impairments in learning and memory have been associated with an age-dependent decline in forebrain of cholinergic function, and recent evidence indicates that the cholinergic neurons in the nucleus basalis magnocellularis, the septal-diagonal band area and the striatum undergo age-dependent atrophy. Thus, as in Alzheimer-type dementia in man, degenerative changes in the forebrain cholinergic system may contribute to age-related cognitive impairments in rodents. The cause of these degenerative changes is not known. Recent studies have shown that the central cholinergic neurons in the septal-diagonal band area, nucleus basalis and striatum are sensitive to the neurotrophic protein nerve growth factor (NGF). In particular, intraventricular injections or infusions of NGF in young adult rats have been shown to prevent retrograde neuronal cell death and promote behavioural recovery after damage to the septo-hippocampal connections. It is so far not known, however, whether the atrophic cholinergic neurons in aged animals are responsive to NGF treatment. We report here that continuous intracerebral infusion of NGF over a period of four weeks can partly reverse the cholinergic cell body atrophy and improve retention of a spatial memory task in behaviourally impaired aged rats.read more
Citations
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Nuclear factor κB/p49 is a negative regulatory factor in nerve growth factor-induced choline acetyltransferase promoter activity in PC12 cells
TL;DR: Data indicate that p49 is a negative regulator of ChAT expression and suggest a possible mechanism for aging‐associated declines in cholinergic function.
Journal ArticleDOI
NG-011 and NG-012 novel potentiators of nerve growth factor. II: The structure determination of NG-011 and NG-012
TL;DR: Two novel potentiators of nerve growth factor were isolated from the culture broth of Penicillium verruculosum F-4542 and their structures were elucidated by their spectral analysis and degradation experiments.
Journal ArticleDOI
Par-4 inhibits choline uptake by interacting with CHT1 and reducing its incorporation on the plasma membrane.
TL;DR: Kinetic and cell-surface biotinylation assays showed that Par-4 inhibited ChT1-mediated choline uptake by reducing CHT1 expression in the plasma membrane without significantly altering the affinity ofCHT1 for choline or HC-3.
Journal ArticleDOI
Early nerve growth factor-induced events in developing rat septal neurons.
TL;DR: The bilaminar culture system is a useful system for the study of early events in NGF-activated signal transduction and the nature of glial-derived trophic support of developing basal forebrain neurons is suggested.
Journal ArticleDOI
Effects of cholinergic deafferentation and NGF on brain electrical coherence
Daniel P. Holschneider,Andrew F. Leuchter,Oscar U. Scremin,David M. Treiman,David M. Treiman,Nancy Y. Walton,Nancy Y. Walton +6 more
TL;DR: The results suggest that coherence is sensitive to cholinergic deafferentation, particularly of long corticocortical connections, and suggests that brain function in Alzheimer's disease related to damage of transcallosal fiber tracts may not be responsive toCholinergic treatments.
References
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Journal ArticleDOI
Developments of a water-maze procedure for studying spatial learning in the rat
TL;DR: Developments of an open-field water-maze procedure in which rats learn to escape from opaque water onto a hidden platform are described, suggesting that they may lend themselves to a variety of behavioural investigations, including pharmacological work and studies of cerebral function.
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The Cholinergic Hypothesis of Geriatric Memory Dysfunction
Raymond T. Bartus,Raymond T. Bartus,Reginald L. Dean,Bernard Beer,Bernard Beer,Arnold S. Lippa,Arnold S. Lippa +6 more
TL;DR: Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed and an attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature.
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Book reviewHandbook of Chemical Neuroanatomy: Methods in Chemical Neuroanatomy. Edited by A. Bjorklund and T. Hokfelt. Elsevier, Amsterdam, 1983. Cloth bound, 548 pp. UK £140. (Volume 1 in the series).
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Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections
TL;DR: It is suggested that fimbrial transections resulted in retrograde degeneration of cholinergic septo-hippocampal neurons and that NGF treatment strongly attenuated this lesion-induced degeneration.
Journal ArticleDOI
Nerve growth factor treatment after brain injury prevents neuronal death
TL;DR: Cholinergic neuronal degeneration after axotomy has been proposed to be due to the loss of a retrogradely transported neurotrophic factor, possibly nerve growth factor (NGF), and NGF was continuously infused into the lateral ventricles of adult rats that had received bilateral lesions of all cholinergic axons projecting from the medial septum to the dorsal hippocampus.