PMID- 12485622
OWN - NLM
STAT- MEDLINE
DCOM- 20030320
LR  - 20200106
IS  - 0736-5748 (Print)
IS  - 0736-5748 (Linking)
VI  - 20
IP  - 7
DP  - 2002 Nov
TI  - Influence of neurotrophins on the synaptogenesis of inner hair cells in the deaf 
      Bronx waltzer (bv) mouse organ of Corti in culture.
PG  - 537-54
AB  - The Bronx waltzer (bv) deaf mouse is characterized by massive degeneration of the 
      primary auditory receptors, the inner hair cells, which occurs during the time of 
      expected afferent synaptogenesis. The process is associated with degeneration and 
      protracted division of the normally postmitotic afferent spiral ganglion neurons. 
      To investigate the potential role of neurotrophins in the afferent synaptogenesis 
      of inner hair cells, we exposed bv newborn cochleas in organotypic culture to 
      brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth 
      factor (NGF), and also to gamma aminobutyric acid (GABA), for up to 8 days. The 
      study was done using light and electron microscopy. Only about 20% of the inner 
      hair cells survived in culture, regardless of the treatment, similar to the 
      number in the intact mutant in our colony. Depending on the exogenous treatment, 
      this population consisted of either innervated ultrastructurally normal cells or 
      denervated dedifferentiated cells wrapped-in lieu of nerve endings-by the 
      supporting inner phalangeal and border cells. In the control and GABA cultures, 
      inner hair cells were mostly denervated. BDNF and NT-3 alone or combined 
      increased synaptogenesis and hair cell survival only during the first 3 days (by 
      about 10%); however, the cells became denervated by 8 postnatal (PN). Only NGF 
      induced stable innervation and differentiation of neurosensory relationships, 
      including supernumerary innervation characteristic of the intact bv. Denervation 
      among the remaining 20% of inner hair cells induced a reactive wrapping by inner 
      phalangeal and border cells which evidently extended inner hair cell survival. 
      Immunocytochemical studies of these reactive supporting cells were done in the 
      intact (8 PN) mutant cochlea. The supporting cells that provide sustenance to the 
      denervated inner hair cells displayed strong BDNF (and possibly NT-3) 
      immunoreactivity. Subsequently, we revealed the presence of all three 
      neurotrophins in the inner hair cell region of the developing (1-8 PN) cochlea of 
      the normal ICR mouse. The inner hair cells expressed all three neurotrophins; 
      BDNF prevailed in the inner phalangeal cells, NT-3 in the pillar cells and inner 
      phalangeal cells, and NGF in the pillar cells. IN CONCLUSION: initially, the 80% 
      loss of inner hair cells is apparently caused by their failed afferent 
      synaptogenesis. Exogenous neurotrophins influence synaptogenesis in the bv in 
      culture, but NGF alone is successful in promoting stable neurosensory 
      relationships. The presence of neurotrophins in supporting cells in the normal 
      and degenerating cochlea indicates their role in the sustenance of inner hair 
      cells.
FAU - Sobkowicz, Hanna M
AU  - Sobkowicz HM
AD  - Neurology Department, University of Wisconsin, 1300 University Avenue, Room 75 
      MSC, Madison 53706, USA. hmsobkow@facstaff.wisc.edu
FAU - August, Benjamin K
AU  - August BK
FAU - Slapnick, Susan M
AU  - Slapnick SM
LA  - eng
GR  - R01 DC00844/DC/NIDCD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Dev Neurosci
JT  - International journal of developmental neuroscience : the official journal of the 
      International Society for Developmental Neuroscience
JID - 8401784
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neurotrophin 3)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - Aging/drug effects/*physiology
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cell Count
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cell Survival
MH  - Deafness/physiopathology
MH  - Hair Cells, Auditory, Inner/abnormalities/drug 
      effects/*physiopathology/*ultrastructure
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Nerve Degeneration/drug therapy/embryology/pathology
MH  - Nerve Growth Factor/pharmacology
MH  - Nerve Growth Factors/*pharmacology
MH  - Neurotrophin 3/pharmacology
MH  - Organ of Corti/abnormalities/drug effects/ultrastructure
MH  - Reference Values
MH  - Synapses/drug effects/*physiology/*ultrastructure
MH  - gamma-Aminobutyric Acid/pharmacology
EDAT- 2002/12/18 04:00
MHDA- 2003/03/21 04:00
CRDT- 2002/12/18 04:00
PHST- 2002/12/18 04:00 [pubmed]
PHST- 2003/03/21 04:00 [medline]
PHST- 2002/12/18 04:00 [entrez]
AID - S0736574802000849 [pii]
AID - 10.1016/s0736-5748(02)00084-9 [doi]
PST - ppublish
SO  - Int J Dev Neurosci. 2002 Nov;20(7):537-54. doi: 10.1016/s0736-5748(02)00084-9.