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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Journal ArticleDOI
Stability of septohippocampal neurons following excitotoxic lesions of the rat hippocampus
TL;DR: It is demonstrated that removal of hippocampal target neurons does not alter the number, morphology, or projections of both cholinergic and noncholinergic septal/diagonal band neurons.
Journal ArticleDOI
Effects of transferrin receptor antibody—NGF conjugate on young and aged septal transplants in oculo
C. Backman,P.T. Biddle,Ted Ebendal,Phillip M. Friden,Greg A. Gerhardt,M.A. Henry,Ludmila Mackerlova,Stine Söderström,Ingrid Strömberg,Lee R. Walus,Barry Hoffer,A C Granholm +11 more
TL;DR: The present results suggest that peripheral OX-26-NGF can deliver biologically active NGF across the blood-brain barrier and have dose-dependent positive effects on both aged and developing cholinergic neurons in septal transplants.
Journal ArticleDOI
Nerve growth factor induces galanin gene expression in the rat basal forebrain: implications for the treatment of cholinergic dysfunction.
TL;DR: The results suggest that the concurrent induction of GAL in the BF could limit the ameliorating actions of NGF on cholinergic dysfunction, and provide the first evidence that in vivo NGF administration up‐regulates GAL gene expression in theCholinergic BF.
Journal ArticleDOI
Differential Effects of Nerve Growth Factor on Expression of Choline Acetyltransferase and Sodium-Coupled Choline Transport in Basal Forebrain Cholinergic Neurons in Culture
Julie L. Pongrac,R. Jane Rylett +1 more
TL;DR: Results suggest that regulation of ACh synthesis in primary cultures of basal forebrain neurons is not limited by provision of choline by the high-affinity choline transport system and that increased ChAT activity in the presence of NGF without a concomitant increase in high‐affinity ChAT transport is sufficient to increase A Ch synthesis.
Journal ArticleDOI
ERK-mediated NGF signaling in the rat septo-hippocampal pathway diminishes with age
TL;DR: This rapid NGF signaling pathway is diminished in aged rats compared to young ones and may contribute to memory deficits observed in aged Rats.
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.
Journal ArticleDOI
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.