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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Hypertrophy of basal forebrain neurons and enhanced visuospatial memory in perinatally choline-supplemented rats.
TL;DR: Data are consistent with the hypothesis that supplementation with choline chloride during early development leads to an increase in the size of cell bodies of NTR-immunoreactive cells in the basal forebrain and that this change may contribute to long-term improvement in spatial memory.
Journal ArticleDOI
Reversible schwann cell hyperplasia and sprouting of sensory and sympathetic neurites after intraventricular administration of nerve growth factor
Jürgen Winkler,Jürgen Winkler,Gilbert Ramirez,Gilbert Ramirez,H. Georg Kuhn,Daniel A. Peterson,Patricia Ann Day-Lollini,Gregory R. Stewart,Mark H. Tuszynski,Mark H. Tuszynski,Fred H. Gage,Leon J. Thal,Leon J. Thal +12 more
TL;DR: Findings suggest that better temporal and spatial delivery systems for NGF must be explored to limit potential undesirable side effects while maintaining the survival and function of diseased basal forebrain cholinergic neurons.
Journal ArticleDOI
Growth-factor gene therapy for neurodegenerative disorders
TL;DR: One of these prospective therapies: growth-factor gene therapy for Alzheimer's disease is reviewed, an approach that is currently the subject of a phase I clinical trial and other disease targets for gene therapy will also be discussed.
Journal ArticleDOI
Neural Transplantation in Animal Models of Dementia
TL;DR: It is concluded that although neural transplantation does not offer any immediate prospect of therapeutic repair in clinical dementia, the technique does offer a powerful neurobiological tool for studying the neuropathological processes involved in both spontaneous degeneration and specific diseases of ageing.
Journal ArticleDOI
Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons
Gillian F. O'Meara,Urania Coumis,Shuang Y. Ma,Jan Kehr,Sally Mahoney,Andrea Bacon,Shelley J Allen,Fiona E. Holmes,Ulrika Kahl,Fu H. Wang,Ian R. Kearns,Sven Ove-Ogren,David Dawbarn,Elliott J. Mufson,Ceri H. Davies,Gerard R. Dawson,David Wynick +16 more
TL;DR: It is reported that a third of cholinergic neurons in the medial septum and vertical limb diagonal band of the basal forebrain of adult mice carrying a targeted loss-of-function mutation in the galanin gene are lost, providing unexpected evidence that galan in plays a trophic role to regulate the development and function of a subset of septohippocampal cholinergy neurons.
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.