Afferent regulation of oxidative stress in the chick cochlear nucleus.
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.
Nicholas
A H
AH
Department of Psychology, Program in Neuroscience, Florida State University, Tallahassee, FL 32306-1270, USA.
Hyson
R L
RL
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001306:Auditory Pathways / Q000502:physiology*; D002645:Chickens; D017626:Cochlear Nucleus / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*