Nerve growth factor (NGF) reverses axotomy-induced decreases in choline acetyltransferase, NGF receptor and size of medial septum cholinergic neurons

Hagg, Theo; Fass-Holmes, Barry; Hl, Vahlsing; Manthorpe, Marston; Jm, Conner; Varon, Silvio

doi:10.1016/0006-8993(89)90112-1

Cited by 187 publications

(80 citation statements)

References 26 publications

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“…This lesion thus shows many features, including the time course of changes and the magnitude of cell loss, with the fimbria-fornix lesion model, which is the standard in vivo test for the neuroprotective effect of NGF on forebrain cholinergic neurons. It is of particular interest that GDNF had a significant protective effect also when it was given as a single dose at a time when the lesioned nigral neurons still survived in a shrunken, atrophic state (7 days postlesion), which is similar to what has been observed with NGF in the fimbria-fornix lesion model (31). There is thus a rapidly growing body of evidence that GDNF or a related molecule within the TGF-,B family may play a role as an endogenous survival factor for nigral dopamine neurons, with actions similar to those of NGF on forebrain cholinergic neurons.…”

Section: Discussionsupporting

confidence: 67%

“…In contrast to the rapid cell death (within hours) observed after administration of 6-OHDA at or close to the nigral cell bodies (26)(27)(28), cell death induced by axon terminal damage in the present lesion paradigm does not appear before 1 week postlesion, is preceded by cellular atrophy, and progresses at a slow rate (15). The marked protective effect of GDNF under these conditions compares favorably with the complete sparing from progressive cell loss in GDNF-treated long-term nigral cell cultures (3) or with the protective effect of nerve growth a factor (NGF) on the delayed septal cholinergic cell death seen after distal axotomy of the fimbria (18,(29)(30)(31).…”

Section: Discussionmentioning

confidence: 67%

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Glial cell line-derived neurotrophic factor but not transforming growth factor beta 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion.

Sauer

Rosenblad

Björklund

1995

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

349

195

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Glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor j33 Parkinson disease is one of the most common neurological disorders of the elderly. It is characterized by a progressive degeneration of the dopaminergic neurons in the substantia nigra of the midbrain, leading to a loss of dopamine in the striatum, which constitutes the main projection field of these cells. Although therapeutically relevant augmentation of striatal dopamine can be achieved by drug therapy or intrastriatal transplantation of fetal dopaminergic neurons (1), there is at present no means by which the primary nigral degeneration can be halted. Neurotrophic factors capable of sustaining the survival of otherwise degenerating dopamine neurons are thus of considerable interest (2). GDNF was initially purified and cloned as a potent neurotrophic factor for cultured dopaminergic neurons of the developing substantia nigra (3), and it has been shown that the related transforming growth factors 32 and ,B3 (TGF-f32 and TGF-f33) exert a similar survival-promoting activity on this cell population in vitro (4-6). The expression patterns of GDNF, TGF-j32, and TGF-,B3 mRNAs in the developing rat striatum and substantia nigra further support the notion that one or several of these factors play important physiological roles for immature nigral dopamine neurons (4, 7-9). More recently, administration of GDNF to the basal ganglia has been shown to partially attenuate the disappearance of tyrosine hydroxylase (TH)-immunoreactive nigral neurons following surgical axotomy (10) and the acute toxic effects of systemic doses of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in adult mice (11) or of intracerebral 6-hydroxydopamine (6-OHDA) in rats (12).The aim of the present study was (i) to investigate whether GDNF would exert a protective effect in a model of delayed and progressive nigral cell death more closely related to the cell death seen in human Parkinson disease and (ii) to compare GDNF and the related TGF-f33 with respect to their capacity to counteract nigral dopamine cell degeneration in the adult rat brain.To do so, we used a recent modification of the standard 6-OHDA lesion of the rat nigrostriatal projection (13-15). Unilateral 6-OHDA-lesioning of the dopaminergic terminals in the striatum rather than the medial forebrain bundle or the substantia nigra itself produces a delayed and progressive degeneration of ipsilateral nigral dopamine neurons with an onset 1 week after 6-OHDA injection (15). One week prior to striatal 6-OHDA lesion, nigral cells were retrogradely labeled at the site of subsequent striatal toxin injection with the fluorescent retrograde tracer fluorogold. This allows a specific examination of those nigrostriatal neurons projecting to, or through, the focus of the 6-OHDA lesion. For within-animal controls, fluorogold injections were performed bilaterally, and only one of the labeled striata was subsequently lesioned with 6-OHDA. into both striata at sites 1 mm anterior to bregma and 3 mm later...

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 67%

Glial cell line-derived neurotrophic factor but not transforming growth factor beta 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion.

Sauer

Rosenblad

Björklund

1995

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

349

195

View full text Add to dashboard Cite

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“…This finding, however, is inconsistent with the role proposed for c-Jun in medial septal neurons (MSN) after transection of the fimbria-fornix (44). Whereas SNc neurons degenerate within weeks after axotomy (14), MSN neurons may survive for an extended period before dying (10,11,30). The disparity in rates of survival in these two populations of CNS neurons may be related to the induction of IEG expression in the axotomized neurons.…”

Section: C-jundn Attenuates Striatal Dopaminergic Fiber Degeneration mentioning

confidence: 84%

c-Jun mediates axotomy-induced dopamine neuron death in vivo

Crocker

Lamba

Smith

et al. 2001

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

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“…Axotomy of medial septal cholinergic neurons results in cell atrophy and eventual death that is ameliorated by NGF delivery within the first week [82][83][84]. Delayed NGF treatment cannot completely prevent cell loss, although it can restore cell size and neurotransmitter expression in a large proportion of medial septal cholinergic neurons [82,83,85].…”

Section: Neurotrophins Development and Survivalmentioning

confidence: 99%

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Hollis

Tuszynski

2011

Neurotherapeutics

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Spinal cord injury permanently disrupts neuroanatomical circuitry and can result in severe functional deficits. These functional deficits, however, are not immutable and spontaneous recovery occurs in some patients. It is highly likely that this recovery is dependent upon spared tissue and the endogenous plasticity of the central nervous system. Neurotrophic factors are mediators of neuronal plasticity throughout development and into adulthood, affecting proliferation of neuronal precursors, neuronal survival, axonal growth, dendritic arborization and synapse formation. Neurotrophic factors are therefore excellent candidates for enhancing axonal plasticity and regeneration after spinal cord injury. Understanding growth factor effects on axonal growth and utilizing them to alter the intrinsic limitations on regenerative growth will provide potent tools for the development of translational therapeutic interventions for spinal cord injury.Keywords Neurotrophin . spinal cord injury . regeneration . axon plasticity . functional recovery Human Spinal Cord InjuryTraumatic injury of the spinal cord can produce a range of debilitating effects and permanently alter the capabilities and quality of life of its surviving victims. Damage to the central nervous system (CNS) in general results in destruction of neuronal circuitry. Contusion, compression, and penetration injuries of the spinal cord can interrupt the flow of sensory and motor information between the brain and periphery [1]. Depending on the location and severity of the injury, deficits can range from weakness of limb movement to total paralysis and ventilator-assisted respiration. Spontaneous functional recovery is limited, but can and often does occur in patients with initial sparing of sensorimotor function [2]. This recovery, which plateaus between 12 to 18 months, is very likely due to sparing and sprouting of axons within the zone of partial preservation, an area where some motor function remains intact, immediately adjacent to the lesion site [2].Approximately 40% of humans that sustain spinal cord injury (SCI) exhibit improvement from their early postinjury baseline, and this spontaneous recovery can range from modest to extensive [2]. Spontaneous recovery primarily appears to depend on the extent of tissue sparing at the injury site, allowing compensatory axonal sprouting and systems reorganization at levels ranging from the spinal cord to the cerebral cortex [3][4][5][6][7][8][9][10]. However, in cases of more severe injuries, means of enhancing endogenous levels of axonal sprouting and inducing true axonal regeneration are required to enhance functional outcomes.Electronic supplementary material The online version of this article

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Nerve growth factor (NGF) reverses axotomy-induced decreases in choline acetyltransferase, NGF receptor and size of medial septum cholinergic neurons

Cited by 187 publications

References 26 publications

Glial cell line-derived neurotrophic factor but not transforming growth factor beta 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion.

Glial cell line-derived neurotrophic factor but not transforming growth factor beta 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion.

c-Jun mediates axotomy-induced dopamine neuron death in vivo

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

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