Afferent regulation of oxidative stress in the chick cochlear nucleus

doi:10.1016/j.neuroscience.2006.03.015

Neuroscience

Volume 140, Issue 4, 2006, Pages 1359-1368

https://doi.org/10.1016/j.neuroscience.2006.03.015 Get rights and content

Abstract

The chick auditory brain stem has been a useful model system for examining the afferent-dependent signals that regulate postsynaptic neurons. Like other sensory systems, compromised afferent input results in rapid death and atrophy of postsynaptic neurons. The present paper explores the possible contributions of an oxidative stress pathway in determining neuronal fate following deafferentation. Levels of reactive oxygen species, lipid damage measured by 4-hydroxynonenal formation, and a compensatory reactive oxygen species-induced response regulated by glutathione s transferase M1 and the reactive oxygen species-sensitive transcriptional factor, nuclear respiratory factor 1 were examined. Unilateral cochlea removal surgery was performed on young posthatch chicks. Labeling in the cochlear nucleus, nucleus magnocellularis, on opposite sides of the same tissue sections were compared by densitometry. The results showed a dramatic increase in reactive oxygen species in the deafferented nucleus magnocellularis by 6 h following cochlea removal. This increase in reactive oxygen species was accompanied by lipid damage and a compensatory upregulation of both glutathione s transferase M1 and nuclear respiratory factor 1. Double-labeling revealed that glutathione s transferase M1 expression was highest in neurons that were likely to survive deafferentation, as assessed immunocytochemically with Y10b, a marker for ribosomal integrity. Together, these data suggest reactive oxygen species are generated and a compensatory detoxifying pathway is upregulated in the first few hours following deafferentation. This is consistent with the hypothesis that oxidative stress plays a role in determining whether a given neuron survives following deafferentation.

Section snippets

Subjects

All subjects were Ross×Ross chickens that were hatched and reared at Florida State University. The procedures used in these experiments were approved by the Animal Care and Use Committee at The Florida State University and conform to the guidelines set forth by the National Institutes of Health. All efforts were made to minimize the number of animals used and their potential suffering. Subjects were 7–10 days posthatch for the experiments using immunocytochemistry. This age was chosen because

Deafferentation-induced elevation in levels of ROS

Unilateral cochlea removal resulted in a transient rise in levels of ROS in the NM neurons. An example of this effect is shown in Fig. 1. Approximately 6–8 h following cochlea removal, deafferented NM neurons exhibit elevated levels of ROS. Opposite sides of the same tissue section were compared for analysis and these objective analyses of staining density confirmed the visual impressions. A two-way mixed analysis of variance (ANOVA) was performed on the gray scale density measurements using

Discussion

The chick brain stem provides a valuable model to explore a possible novel pathway in which ROS could potentially influence cell survival and death following the loss of afferent input. The primary rationale for pursuing the present study was that previous reports indicate a rapid increase in intracellular calcium (Zirpel et al., 1995) and a dramatic mitochondrial proliferation in NM following deafferentation (Hyde and Durham, 1994). It was then hypothesized that deafferentation will lead to a

Acknowledgments

This work was supported by NIH grant DC00858.

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Sensory systemAfferent regulation of oxidative stress in the chick cochlear nucleus

Abstract

Section snippets

Subjects

Deafferentation-induced elevation in levels of ROS

Discussion

Acknowledgments

Mol Aspects Med

Free Radic Biol Med

Arch Biochem Biophys

Biochem Biophys Res Commun

J Biol Chem

Comp Biochem Physiol B

Prog Neuropsychopharmacol Biol Psychiatry

J Biol Chem

Mol Aspects Med

Cancer Lett

Brain Res

Brain Res

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Neurosci Lett

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J Biol Chem

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Sensory system
Afferent regulation of oxidative stress in the chick cochlear nucleus