title: Immunohistological analysis of neurturin and its receptors in human cochlea.
abstract: OBJECTIVE
  Difficulties in obtaining properly preserved human cochlea have been a major obstacle to in vitro study of this deeply located and hard bone-fortressed hearing organ. Our study aimed at investigating GDNF family ligands (GFLs) and their receptors in the human cochleae that were surgically obtained during a transcochlear approach dealing with life-threatening, intra-cranial meningiomas.
  
  
  METHODS
  The specimens were properly fixed with 4% paraformaldehyde in the operating room. By using immunohistochemical techniques, distribution of GDNF, Neurturin (NTN, one member of GFLs), as well as cRet, GFRα-1 and GFRα-2 receptors in the human cochleae was investigated. Five cochleae from five adult patients were processed for the study. The patients had normal hearing threshold before operation.
  
  
  RESULTS
  cRet receptor immunoreactivity was seen in the spiral ganglion neurons, mainly inside the cell bodies but rarely in the nerve fibers and not in the organ of Corti. Immunolabeling for GFRα-1 and GFRα-2 receptors was identified mainly in the cell bodies of the spiral neurons than in the nerve fibers. In the organ of Corti, GFRα-1 immunostaining could be demonstrated in the Deiters' cells, Hensen cells, inner pillar cells, and weakly in the inner hair cells but not in the outer hair cells; no structures in the organ of Corti were labeled with GFRα-2 receptor antibody. NTN immunostaining was found in the supporting cells of organ of Corti, including Deiters' cells, Hensen cells as well as Claudius' cells. In the spiral ganglia, NTN immunostaining was seen in both the cell bodies and the nerve fibers of neurons. GDNF immunoreactivity was not revealed in human cochlea.
  
  
  CONCLUSIONS
  Surgically obtained human cochleae were properly fixed and underwent immunohistochemical investigation of neurotrophic elements. NTN and its receptors discovered in current study can be responsible for the unique neuronal survival properties in human spiral ganglion (hSG); a prerequisite for the function of cochlear implants.
authors.affiliation: Department of Surgical Sciences, Section of Otolaryngology, Uppsala University Hospital, 75185 Uppsala, Sweden. Electronic address: lwoo24@gmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Surgical Sciences, Section of Otolaryngology, Uppsala University Hospital, 75185 Uppsala, Sweden.
authors.forename: Helge
authors.initials: H
authors.lastname: Rask-Andersen
mesh_terms: D000328:Adult; D000368:Aged; D003051:Cochlea / Q000378:metabolism*; D005260:Female; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism*; D006198:Hair Cells, Auditory / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D051101:Neurturin / Q000378:metabolism*; D009925:Organ of Corti / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism*; D013136:Spiral Ganglion / Q000166:cytology / Q000378:metabolism
chemical_list: C494987:GFRA1 protein, human; C494990:GFRA2 protein, human; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C495053:NRTN protein, human; D051101:Neurturin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: GDNF family ligand; GFRα-1; GFRα-2; Human cochlea; Neurturin; Spiral ganglion neuron; cRet