Peripheral nerve injury has effects that extend beyond damaged neurons. However, the impact of injury on neighboring sensory fields is not well understood. We propose that immune cells, or "leukocytes", mediate changes in taste function. Macrophages respond to nerve injury, and extend to uninjured regions of the tongue. These leukocytes are predictive of normal neural taste responses. Neutrophils are also part of the immune response to injury, but they appear to have a negative effect on taste function. Neural injury alters sodium transduction in taste receptor cells, suggesting that the epithelial sodium channel (ENaC) is the site of functional plasticity. We will test the following hypotheses: (1) Neutrophils are the initial immune responders to gustatory nerve injury, and they induce deficits in taste function;(2) Nerve injury and leukocytes modulate ENaC expression and/or function;and (3) IL-12, a proinflammatory cytokine, maintains normal taste function after injury by promoting a balanced immune response. Resolution of these hypotheses will increase our understanding of dynamic immune responses to neural injury and their beneficial and harmful effects on sensory receptor cells.

Public Health Relevance

The immune system plays an important role following neural injury, but its response to degeneration in the taste system is not well-understood. The proposed studies will determine the effects of an imbalanced immune response on taste function, and the mechanisms for immune-taste receptor cell interactions. Better understanding of the beneficial and harmful effects of the immune response to injury will lead to new strategies to promote normal sensory function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC005811-10
Application #
8413453
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2002-12-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
10
Fiscal Year
2013
Total Cost
$255,949
Indirect Cost
$81,834
Name
Georgia Regents University
Department
Neurology
Type
Schools of Medicine
DUNS #
966668691
City
Augusta
State
GA
Country
United States
Zip Code
30912
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Guagliardo, Nick A; West, Katie Nicole; McCluskey, Lynnette P et al. (2009) Attenuation of peripheral salt taste responses and local immune function contralateral to gustatory nerve injury: effects of aldosterone. Am J Physiol Regul Integr Comp Physiol 297:R1103-10
Wall, Pamela Lea; McCluskey, Lynnette Phillips (2008) Rapid changes in gustatory function induced by contralateral nerve injury and sodium depletion. Chem Senses 33:125-35
Cavallin, Melissa Ann; McCluskey, Lynnette Phillips (2007) Upregulation of the chemokine monocyte chemoattractant protein-1 following unilateral nerve injury in the peripheral taste system. Neurosci Lett 413:187-90
Cavallin, Melissa Ann; McCluskey, Lynnette Phillips (2007) Upregulation of intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 after unilateral nerve injury in the peripheral taste system. J Neurosci Res 85:364-72
Cavallin, Melissa Ann; McCluskey, Lynnette Phillips (2005) Lipopolysaccharide-induced up-regulation of activated macrophages in the degenerating taste system. J Neurosci Res 80:75-84

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