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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Current advances in using neurotrophic factors to treat neurodegenerative disorders.
TL;DR: Current efforts and advances in resolving challenges in translating the potential of neurotrophins into the therapeutic arena are addressed and an overview of roadmaps for future translational research and neurotrophin-based drug developments are provided.
Journal ArticleDOI
Somatic gene transfer of NGF to the aged brain: behavioral and morphological amelioration
Karen S. Chen,Fred H. Gage +1 more
TL;DR: The results show that naturally occurring age-related memory loss can be reversed by grafting cells engineered to secrete NGF directly to the NBM, and that either cholinergic hyper- or hypofunction may lead to cognitive impairments.
Journal ArticleDOI
Apoptotic cell death induced by optic nerve lesion in the neonatal rat
TL;DR: It is reported that following intracranial transection of the optic nerve in the neonatal rat in vivo, retinal ganglion cells undergo an active, apoptotic cell death, and the administration of protein synthesis inhibitors and cycloheximide prevents the appearance of pyknotic nuclei as well as of fragmented DNA of ganglions at 24 hr postlesion.
Journal ArticleDOI
NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer's disease
TL;DR: In situ hybridization is used to show that NGF-receptor (NGF-R) mRNA-positive neurons are lost within all divisions of the nucleus basalis of Meynert in AD patients as compared to normal aged controls.
Journal ArticleDOI
Reversal of age-dependent cognitive impairments and cholinergic neuron atrophy by NGF-secreting neural progenitors grafted to the basal forebrain
TL;DR: It is demonstrated that locally increased supply of NGF to the basal forebrain cholinergic nuclei has a significant impact on cognitive function and support the usefulness of neural progenitor cells for a long-term localized delivery of neurotrophins to the CNS.
References
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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.