Axotomy abolishes NeuN expression in facial but not rubrospinal neurons

McPhail, Lowell T.; McBride, Christopher B.; McGraw, John J.; Steeves, John D.; Tetzlaff, Wolfram

doi:10.1016/j.expneurol.2003.10.001

Cited by 100 publications

(79 citation statements)

References 12 publications

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“…Loss of NeuN expression occurs in axotomized facial motor neurons but not in axotomized rubrospinal neurons (McPhail et al, 2004a). The TrkB.T1-induced downregulation of NeuN was specific for motor neurons and was not observed in hippocampal neurons.…”

Section: Long-term Expression Of Truncated Trkb Results In Motor Neurmentioning

confidence: 89%

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

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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.

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Section: Long-term Expression Of Truncated Trkb Results In Motor Neurmentioning

confidence: 89%

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

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“…It is interesting to speculate that the time course of the T cell response in the injured FMN may partly be dependent on the ability of the nerve to reconnect. Previously, it was shown that the decreased expression of NeuN in the FMN following facial nerve crush was transient in mice, where the return of NeuN expression coincides with the time when mice generally show a return of whisker function (McPhail et al, 2004b). That this loss of neuronal phenotype failed to return in mice that received facial nerve resection was suggested to be related to the inability of the nerve to reconnect.…”

Section: Discussionmentioning

confidence: 99%

Influence of injury severity on the rate and magnitude of the T lymphocyte and neuronal response to facial nerve axotomy

Ha¹,

Parikh²,

Huang³

et al. 2008

Journal of Neuroimmunology

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The temporal relationship between severity of peripheral axonal injury and T lymphocyte trafficking to the neuronal cell bodies of origin in the brain has been unclear. We sought to test the hypothesis that greater neuronal death induced by disparate forms of peripheral nerve injury would result in differential patterns of T cell infiltration and duration at the cell bodies of origin in the brain and that these measures would correlate with the magnitude of neuronal death over time and cumulative neuronal loss. To test this hypothesis, we compared the time course of CD3 + T cell infiltration and neuronal death (assessed by CD11b + perineuronal microglial phagocytic clusters) following axonal crush versus axonal resection injuries, two extreme variations of facial nerve axotomy that result in mild versus severe neuronal loss, respectively, in the facial motor nucleus. We also quantified the number of facial motor neurons present at 49 days post-injury to determine whether differences in the levels of neuronal death between nerve crush and resection correlated with differences in cumulative neuronal loss. Between 1-7 days post-injury when levels of neuronal death were minimal, we found that the rate of accumulation and magnitude of the T cell response was similar following nerve crush and resection. Differences in the T cell response were apparent by 14 days post-injury when the level of neuronal death following resection was substantially greater than that seen in crush injury. For nerve resection, the peak of neuronal death at 14 days post-resection was followed by a maximal T cell response one week later at 21 days. Differences in the level of neuronal death between the two injuries across the time course tested reflected differences in cumulative neuronal loss at 49 days post-injury. Altogether, these data suggest that the trafficking of T cells to the injured FMN is dependent upon the intensity of peripheral nerve injury and associated neuronal death.

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“…The antibody reacts primarily with the nuclei of most neuronal cell types throughout the nervous system of mice, although few cell types, such as cerebellar Purkinje cells are not reactive (manufacturer's data sheet). The pitfalls of staining with this antiserum are discussed in the literature (McPhail et al, 2004;Ü nal-Ç evik et al, 2004) and also in this manuscript.…”

Section: Immunocytochemical Staining Proceduresmentioning

confidence: 96%

Axotomy induces contrasting changes in calcium and calcium-binding proteins in oculomotor and hypoglossal nuclei of Balb/c mice

2006

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Motor neurons with different susceptibility to degeneration have been identified in amyotrophic lateral sclerosis (ALS). Increase of intracellular calcium has been proposed as a mediator, amplifying the damage through a positive feedback of the known pathological processes. Accordingly, the potential of motor neurons to limit calcium increases during injury might be proportional to their viability. A basic mechanism of reducing calcium amplitudes depends on the calcium-buffering capacity, determined by the calcium-binding protein content. In this study, oculomotor and hypoglossal neurons, prototypes of resistant and vulnerable motor neurons in ALS were examined in axotomy experiments. Total calcium-, parvalbumin-, and calbindin-D28k levels of motor neurons of adult mice were characterized by electron microscopic histochemistry and light microscopic immunostaining. In hypoglossal neurons, compared with oculomotor neurons, larger and more enduring increases of calcium were detected. The perikarya of hypoglossal neurons remained immunonegative for both parvalbumin and calbindin-D28k. Qualitatively, no major cell loss was noted after axotomy, but a decreased neuronal marker staining at days 1-14 suggested a reversible injury of hypoglossal neurons. Oculomotor neurons were not stained for calbindin-D28k but stained for parvalbumin in control conditions, staining which increased at postoperative days 7-14 before returning to baseline. Neuronal marker staining did not change in these cells during the observed period. The higher level of parvalbumin in resistant motor neurons and their ability to up-regulate parvalbumin after injury, paralleled by a smaller increase of intracellular calcium suggest that parvalbumin may have a protective effect in these cells.

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Axotomy abolishes NeuN expression in facial but not rubrospinal neurons

Cited by 100 publications

References 12 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

Influence of injury severity on the rate and magnitude of the T lymphocyte and neuronal response to facial nerve axotomy

Axotomy induces contrasting changes in calcium and calcium-binding proteins in oculomotor and hypoglossal nuclei of Balb/c mice

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