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Published on: January 9, 2019
The influence of chronic lithium administration on deafferentation-induced cellular changes in the chick cochlear
A L Bush1, K L Carzoli, R L Hyson
1Department of Psychology, The Florida State University, 1107 West Call Street, Tallahassee, FL 32306-4301, USA.
Abstract:
The avian brainstem serves as a useful model system to address the question of how afferent activity influences viability of target neurons. Approximately 20-30% of neurons in the chick cochlear nucleus, nucleus magnocellularis (NM) die following deafferentation (i.e. deafness produced by cochlea removal). Previous studies have identified cellular events that occur within hours following cochlea removal, which are thought to lead to the ultimate death of NM neurons. We have recently shown that chronic lithium treatment increases neuronal survival following deafferentation. To assess where in the cell death cascade lithium is having its effect, we evaluated some of the early deafferentation-induced cellular changes in NM neurons. Lithium did not affect deafferentation-induced changes that occur across the entire population of NM neurons. There were still deafferentation-induced increases in intracellular calcium concentrations and early changes in the ribosomes, as indicated by Y10b immunolabeling. Lithium did, however, affect changes that are believed to be indicative of the subpopulation of NM neurons that will eventually die. Ribosomes recovered in all of the deafferented NM neurons (as assessed by Y10b labeling) by 10 h following cochlea removal in subjects pretreated with lithium, while a subpopulation of the NM neurons in saline-treated subjects showed dramatic reduction in Y10b labeling at that time. Lithium treatment also prevented the robust upregulation of b cell leukemia/lymphoma-2 (Bcl-2) mRNA that is observed in a subpopulation of deafferented NM neurons 6 h following cochlea removal.
Insights
Chronic lithium treatment enhances neuronal survival in the avian brainstem after deafferentation. Lithium specifically impacts early cellular changes in vulnerable neurons, preventing ribosome loss and bcl-2 mRNA upregulation.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- The avian brainstem, specifically the nucleus magnocellularis (NM), is a model for studying how afferent activity impacts neuronal survival.
- Deafferentation, such as cochlea removal, leads to significant neuronal death (20-30%) in the chick NM.
- Early cellular events following deafferentation are implicated in NM neuron death.
Purpose of the Study:
- To investigate the cellular mechanisms by which lithium promotes neuronal survival following deafferentation.
- To determine if lithium affects early deafferentation-induced cellular changes in NM neurons.
Main Methods:
- Chickens underwent cochlea removal (deafferentation) with or without chronic lithium pretreatment.
- Evaluated early cellular changes in NM neurons, including intracellular calcium levels and ribosome integrity (Y10b immunolabeling).
- Assessed the expression of bcl-2 mRNA in deafferented NM neurons.
Main Results:
- Lithium did not alter deafferentation-induced increases in intracellular calcium or early ribosome changes across all NM neurons.
- Lithium treatment prevented the reduction in Y10b labeling (indicating ribosome recovery) in a subpopulation of NM neurons by 10 hours post-deafferentation.
- Lithium administration blocked the upregulation of bcl-2 mRNA in a subpopulation of deafferented NM neurons at 6 hours post-deafferentation.
Conclusions:
- Lithium selectively affects cellular changes associated with the subpopulation of NM neurons destined to die after deafferentation.
- Lithium's neuroprotective effect appears to involve modulating ribosome integrity and bcl-2 mRNA expression in vulnerable neurons.
