Up-regulation of GDNFR-α and c-ret mRNA in facial motor neurons following facial nerve injury in the rat

被引:35
作者
Burazin, TCD [1 ]
Gundlach, AL [1 ]
机构
[1] Univ Melbourne, Austin & Repatriat Med Ctr, Dept Med, Clin Pharmacol & Therapeut Unit, Heidelberg, Vic 3084, Australia
来源
MOLECULAR BRAIN RESEARCH | 1998年 / 55卷 / 02期
基金
英国医学研究理事会;
关键词
glial cell line-derived neurotrophic factor; GDNFR-alpha; c-ret; receptor tyrosine kinase; motor neuron; axotomy; in situ hybridization histochemistry;
D O I
10.1016/S0169-328X(98)00017-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Glial cell line-derived neurotrophic factor (GDNF), a powerful trophic factor for developing, and injured adult motor neurons, has recently been shown to mediate its physiological effects via a multi-component receptor system comprising the GDNFR-alpha binding protein and the c-rer receptor tyrosine kinase. Using in situ hybridization histochemistry this study investigated whether adult motor neurons express mRNAs encoding GDNFR-alpha and c-ret, and explored possible time-dependent changes in these mRNA species following facial nerve resection and crush injury. Levels of mRNA for the signaling component of the GDNF receptor, c-ret, were increased similar to 1.4-fold in the ipsilateral facial nucleus, 1 and 3 days after unilateral facial nerve crush and resection, but returned to contralateral levels by 7-21 days. GDNFR-alpha mRNA was increased from 2 to 3-fold in the facial nucleus at 1 and 3 days after facial nerve crush and to similar, but more sustained (up to 21 days), levels after resection. In contrast, GDNF mRNA was not detectable in normal or injured facial motor neurons. The gradual return of c-ret and GDNFR-alpha mRNAs to control levels 21 days after facial nerve crush, parallels the axonal regeneration process, while nerve damage by resection has more severe consequences compared to nerve crush, reflected by the prolonged time course of increased GDNFR-alpha mRNA, similar to markers such as the NGF-receptor, galanin and GAP-43. These findings confirm the importance of GDNF trophic/signaling systems after nerve injury and suggest the potential for broad biological and therapeutic actions of GDNF or related factors in the CNS, particularly on damaged motor neurons. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:331 / 336
页数:6
相关论文
共 26 条
  • [1] GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo
    Arenas, E
    Trupp, M
    Akerud, P
    Ibanez, CF
    [J]. NEURON, 1995, 15 (06) : 1465 - 1473
  • [2] AVANTAGGIATO V, 1994, CELL GROWTH DIFFER, V5, P305
  • [3] Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase
    BujBello, A
    Adu, J
    Pinon, LGP
    Horton, A
    Thompson, J
    Rosenthal, A
    Chinchetru, M
    Buchman, VL
    Davies, AM
    [J]. NATURE, 1997, 387 (6634) : 721 - 724
  • [4] Rapid and transient increases in cellular immediate early gene and neuropeptide mRNAs in cortical and limbic areas after amygdaloid kindling seizures in the rat
    Burazin, TCD
    Gundlach, AL
    [J]. EPILEPSY RESEARCH, 1996, 26 (01) : 281 - 293
  • [5] CANZIAN F, 1995, MAMM GENOME, V6, P433, DOI 10.1007/BF00355647
  • [6] GDNF mRNA in Schwann cells and DRG satellite cells after chronic sciatic nerve injury
    Hammarberg, H
    Piehl, F
    Cullheim, S
    Fjell, J
    Hokfelt, T
    Fried, K
    [J]. NEUROREPORT, 1996, 7 (04) : 857 - 860
  • [7] GDNF - A POTENT SURVIVAL FACTOR FOR MOTONEURONS PRESENT IN PERIPHERAL-NERVE AND MUSCLE
    HENDERSON, CE
    PHILLIPS, HS
    POLLOCK, RA
    DAVIES, AM
    LEMEULLE, C
    ARMANINI, M
    SIMPSON, LC
    MOFFET, B
    VANDLEN, RA
    KOLIATSOS, VE
    ROSENTHAL, A
    [J]. SCIENCE, 1994, 266 (5187) : 1062 - 1064
  • [8] GDNF-induced activation of the Ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF
    Jing, SQ
    Wen, DZ
    Yu, YB
    Holst, PL
    Luo, Y
    Fang, M
    Tamir, R
    Antonio, L
    Hu, Z
    Cupples, R
    Louis, JC
    Hu, S
    Altrock, BW
    Fox, GM
    [J]. CELL, 1996, 85 (07) : 1113 - 1124
  • [9] A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor
    Klein, RD
    Sherman, D
    Ho, WH
    Stone, D
    Bennett, GL
    Moffat, B
    Vandlen, R
    Simmons, L
    Gu, QM
    Hongo, JA
    Devaux, B
    Poulsen, K
    Armanini, M
    Nozaki, C
    Asai, N
    Goddard, A
    Phillips, H
    Henderson, CE
    Takahashi, M
    Rosenthal, A
    [J]. NATURE, 1997, 387 (6634) : 717 - 721
  • [10] Axotomy as an experimental model of neuronal injury and cell death
    Koliatsos, VE
    Price, DL
    [J]. BRAIN PATHOLOGY, 1996, 6 (04) : 447 - 465