Glial cell line-derived neurotrophic factor and chronic electrical stimulation prevent VIII cranial nerve degeneration following denervation

被引:104
作者
Kanzaki, S
Stöver, T
Kawamoto, K
Prieskorn, DM
Altschuler, RA
Miller, JM
Raphael, Y
机构
[1] Univ Michigan, Kresge Hearing Res Inst, Ann Arbor, MI 48109 USA
[2] Keio Univ, Dept Otolaryngol, Shinjuku Ku, Tokyo 1600016, Japan
[3] Hannover Med Sch, ENT Clin, D-30625 Hannover, Germany
[4] Kansai Med Univ, Dept Otolaryngol, Osaka 5708506, Japan
[5] Karolinska Inst, Dept Otolaryngol, S-17176 Stockholm, Sweden
关键词
gene transfer; growth factors; spiral ganglion; cochlea; guinea pig; cochlear implant;
D O I
10.1002/cne.10480
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
As with other cranial nerves and many CNS neurons, primary auditory neurons degenerate as a consequence of loss of input from their target cells, the inner hair cells (IHCs). Electrical stimulation (ES) of spiral ganglion cells (SGCs) has been shown to enhance their survival. Glial cell line-derived neurotrophic factor (GDNF) has also been shown to increase survival of SGCs following IHC loss. In this study, the combined effects of the GDNF transgene delivered by adenoviral vectors (Ad-GDNF and ES were tested on SGCs after first eliminating the IHCs. Animal groups received Ad-GDNF or ES or both. Ad-GDNF was inoculated into the cochlea of gumea pigs after deafening, to overexpress human GDNF. ES-treated animals were implanted with a cochlear implant electrode and chronically stimulated. A third group of animals received both Ad-GDNF and ES (GDNF/ES). Electrically evoked auditory brainstem responses were recorded from ES-treated animals at the start and end of the stimulation period. Animals were sacrificed 43 days after deafening and their ears prepared for evaluation of IHC survival and SGC counts. Treated ears exhibited significantly greater SGC survival than nontreated ears. The GDNF/ES combination provided significantly better preservation of SGC density than either treatment alone. Insofar as ES parameters were optimized for maximal protection (saturated effect), the further augmentation of the protection by GDNF suggests that the mechanisms of GDNF- and ES-mediated SGC protection are, at least in part, independent. We suggest that GDNF/ES combined treatment in cochlear implant recipients will improve auditory perception. These findings may have implications for the prevention and treatment of other neurodegenerative processes.
引用
收藏
页码:350 / 360
页数:11
相关论文
共 74 条
[41]   Renal and neuronal abnormalities in mice lacking GDNF [J].
Moore, MW ;
Klein, RD ;
Farinas, I ;
Sauer, H ;
Armanini, M ;
Phillips, H ;
Reichardt, LF ;
Ryan, AM ;
CarverMoore, K ;
Rosenthal, A .
NATURE, 1996, 382 (6586) :76-79
[42]  
Mou K, 1998, J COMP NEUROL, V402, P129
[43]  
Mou K, 1997, J COMP NEUROL, V386, P529
[44]   Effects of GDNF on axotomized sensory and motor neurons in adult rats [J].
Munson, JB ;
McMahon, SB .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1997, 9 (06) :1126-1129
[45]   HISTOPATHOLOGIC CORRELATION OF SPIRAL GANGLION-CELL COUNT AND NEW BONE-FORMATION IN THE COCHLEA FOLLOWING MENINGOGENIC LABYRINTHITIS AND DEAFNESS [J].
NADOL, JB ;
HSU, WC .
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 1991, 100 (09) :712-716
[46]   Upregulation of glial cell line-derived neurotrophic factor (GDNF) in the rat cochlea following noise [J].
Nam, YJ ;
Stöver, T ;
Hartman, SS ;
Altschuler, RA .
HEARING RESEARCH, 2000, 146 (1-2) :1-6
[47]  
OTTE J, 1978, LARYNGOSCOPE, V88, P1231
[48]   Defects in enteric innervation and kidney development in mice lacking GDNF [J].
Pichel, JG ;
Shen, LY ;
Sheng, HZ ;
Granholm, AC ;
Drago, J ;
Grinberg, A ;
Lee, EJ ;
Huang, SP ;
Saarma, M ;
Hoffer, BJ ;
Sariola, H ;
Westphal, H .
NATURE, 1996, 382 (6586) :73-76
[49]  
Pong K, 1998, J NEUROCHEM, V71, P1912
[50]   GDNF triggers a novel Ret-independent Src kinase family-coupled signaling via a GPI-linked GDNF receptor α1 [J].
Poteryaev, D ;
Titievsky, A ;
Sun, YF ;
Thomas-Crusells, J ;
Lindahl, M ;
Billaud, M ;
Arumäe, U ;
Saarma, M .
FEBS LETTERS, 1999, 463 (1-2) :63-66