Central infusions of brain-derived neurotrophic factor and , but not nerve growth factor and neurotrophin-3, prevent loss of the cholinergic phenotype in injured adult motor neurons

Tuszynski, Mark H.; Mafong, Erick A.; Meyer, Scott

doi:10.1016/0306-4522(95)00440-8

Cited by 60 publications

(52 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cholinergic marker expression in injured adult motor neurons is regulated by exogenously applied TrkB ligands (Yan et al, 1994;Friedman et al, 1995;Tuszynski et al, 1996;Wang et al, 1997;Fernandes et al, 1998). To determine whether overexpression of TrkB isoforms affected the expression of neuronal markers in mature facial motor neurons, we stained sections of AAVinjected animals with an antibody for NeuN, a nuclear protein with DNA binding properties (Mullen et al, 1992), and an antibody for the neurotransmitter synthesizing enzyme ChAT.…”

Section: Downregulation Of Neuronal Marker Expression In Truncated Trmentioning

confidence: 99%

“…NT-4/5 is the predominant neurotrophin expressed in the targets of mature facial and spinal motor neurons Funakoshi et al, 1995;Griesbeck et al, 1995). Adult motor neurons remain responsive to BDNF, because exogenously applied TrkB ligands maintain the cholinergic phenotype of axotomized adult facial, spinal, and hypoglossal motor neurons (Yan et al, 1994;Friedman et al, 1995;Tuszynski et al, 1996;Wang et al, 1997;Fernandes et al, 1998) and rescue avulsed motor neurons from injury-induced cell death Kishino et al, 1997;Novikov et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Long-Term Adeno-Associated Viral Vector-Mediated Expression of Truncated TrkB in the Adult Rat Facial Nucleus Results in Motor Neuron Degeneration

et al. 2006

View full text Add to dashboard Cite

Adult facial motor neurons continue to express full-length TrkB tyrosine kinase receptor (TrkB.FL), the high-affinity receptor for the neurotrophins BDNF and neurotrophic factor-4/5 (NT-4/5), suggesting that they remain dependent on target-derived and locally produced neurotrophins in adulthood. Studies on the role of TrkB signaling in the adult CNS have been hampered by the early lethality of bdnf, nt-4/5, and trkB knock-out mice. We disrupted TrkB.FL signaling in adult facial motor neurons using adeno-associated viral vector-mediated overexpression of a naturally occurring dominant-negative TrkB receptor, TrkB.T1. Expression of TrkB.T1 resulted in neuronal atrophy and downregulation of NeuN (neuronal-specific nuclear protein) and ChAT expression in facial motor neurons. A subset of transduced neurons displayed signs of motor neuron degeneration that included dendritic beading and rounding of the soma at 2 months of TrkB.T1 expression. Cell counts revealed a significant reduction in motor neuron number in the facial nucleus at 4 months after onset of expression of TrkB.T1, suggesting that a proportion of TrkB.T1-expressing motor neurons became undetectable as a result of severe atrophy or was lost because of cell death. In contrast, overexpression of TrkB.FL did not result in a decrease in facial motor neuron number. Our results indicate that a subset of facial motor neurons remains dependent on TrkB ligands for the maintenance of structural and molecular characteristics in adulthood.

show abstract

Section: Downregulation Of Neuronal Marker Expression In Truncated Trmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long-Term Adeno-Associated Viral Vector-Mediated Expression of Truncated TrkB in the Adult Rat Facial Nucleus Results in Motor Neuron Degeneration

et al. 2006

View full text Add to dashboard Cite

show abstract

“…This opposing effect in the regulation of TrkB and TrkC expression after axotomy has also been reported for other types of motoneuron [60,79,85,[87][88][89]. In addition, the infusion of NT-3 is not as efficient as that of BDNF in preventing the death or the downregulation of cholinergic phenotype in injured motoneurons [88,90,91]. Therefore, as it happened with NGF, NT-3 might also not be a key mediator in the survival and regeneration of rat extraocular motoneurons after lesion.…”

Section: Changes In Expression Of Trk Receptors After Axotomymentioning

confidence: 63%

“…The downregulation of the cholinergic phenotype is a commom phenomenon in lesioned motoneurons [60,86,91,99]. The time course evolution of choline acetyltransferase (ChAT) expression after enucleation (an initial decrease by day 15 followed by a recovery; Figure 3A We can conclude that extraocular motoneurons differentially modify their requirement of neurotrophins as a consequence of their target removal.…”

Section: Correlations With Regenerative and Cholinergic Phenotypesmentioning

confidence: 87%

See 1 more Smart Citation

Complementariness and Functional Parcellation of Neurotrophin Actions on the Oculomotor System

Benítez‐Temiño¹,

Davis-López²,

Morcuende³

et al. 2016

Preprint

View full text Add to dashboard Cite

Abstract:Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF, BDNF or NT-3 protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT. In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review we summarize these evidences and discuss them in the context of other motor systems.

show abstract

TrkA immunoreactive neurones in the rat spinal cord

et al. 1997

View full text Add to dashboard Cite

We report the presence in rat spinal cord of a novel neuronal system expressing tyrosine kinase receptor (trkA), the high affinity receptor for nerve growth factor (NGF). TrkA immunoreactive cell bodies were observed in the intermediate grey matter of the spinal cord and were classified into three main groups: central canal cells located dorsolateral to the aqueduct, partition cells located between lamina X, and the lateral border of the intermediate grey, and a morphologically heterogeneous group which included large cells located near the lateral border. In situ hybridization confirmed that cells in all these areas express trkA mRNA. Combined immunofluorescence and retrograde Fluoro-Gold labelling was used to further characterise the projections and neurotransmitter profile of the trkA cells. Although often located in the vicinity of preganglionic cell groups, trkA immunoreactive cells are not themselves preganglionic. Rather, the central canal and partition cells belong to a neurochemically complex cholinergic propriospinal system. Many partition cells coexpress trkA, choline acetyltransferase (ChAT), the low affinity neurotrophin receptor, p75, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d). In contrast, trkA immunoreactive central canal cells express ChAT, but do not express p75 and only a subpopulation express NADPH-d. The large trkA immunoreactive cells located on the lateral border do not express ChAT. TrkA immunoreactive fibres were also present and were located in the dorsal horn, in the dorsal columns, and in a bundle ventral to the aqueduct. However, double labelling revealed that the trkA immunoreactive fibres are not intrinsic but are primary afferent in origin and coexpress p75. The location of this novel trkA neuronal system is consistent with it having a role in the segmental integration of autonomic outflow. NGF could affect this system by modulating neuronal phenotype and/or synaptic efficacy.

show abstract

Central infusions of brain-derived neurotrophic factor and , but not nerve growth factor and neurotrophin-3, prevent loss of the cholinergic phenotype in injured adult motor neurons

Cited by 60 publications

References 79 publications

Long-Term Adeno-Associated Viral Vector-Mediated Expression of Truncated TrkB in the Adult Rat Facial Nucleus Results in Motor Neuron Degeneration

Long-Term Adeno-Associated Viral Vector-Mediated Expression of Truncated TrkB in the Adult Rat Facial Nucleus Results in Motor Neuron Degeneration

Complementariness and Functional Parcellation of Neurotrophin Actions on the Oculomotor System

TrkA immunoreactive neurones in the rat spinal cord

Contact Info

Product

Resources

About