Interactions of cyclic adenosine monophosphate, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor treatment on the survival and growth of postnatal mesencephalic dopamine neurons in vitro

被引:16
作者
Lara, J [1 ]
Kusano, K [1 ]
House, S [1 ]
Gainer, H [1 ]
机构
[1] NINDS, LNC, Neurochem Lab, NIH, Bethesda, MD 20892 USA
关键词
cAMP; GDNF; BDNF; mesencephalon; dopaminergic neurons; Parkinson's disease; tyrosine hydroxylase; substantia nigra; MAP kinase;
D O I
10.1016/S0014-4886(02)00028-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The survival of rat postnatal mesencephalic dopamine (DA) neurons in dissociated cell cultures was studied by examining the combinatorial effects of dibutyryl cyclic adenosine monophosphate (db-cAMP), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), as well as selective inhibitors of protein kinase A (PKA), and mitogen-activated protein kinase (MAPK). Postnatal DA neurons were maintained for 14 days in vitro, and were identified by immunohistochemistry using tyrosine hydroxylase antibody. The survival and growth of DA neurons was significantly increased by the inclusion of either >100 muM db-cAMP or 10 muM Forskolin plus 100 muM IBMX in the culture medium. Neither 10-50 ng/ml GDNF nor 50 ng/ml BDNF alone significantly increased DA neuron survival in vitro. However, the combined use of GDNF and BDNF did increase DA neuron survival, and the addition of either db-cAMP or IBMX/Forskolin to media containing these neurotrophins markedly increased DA neuron survival and growth. The cAMP inhibitor Rp-cAMP, the cAMP-dependent protein kinase A inhibitor H89, and the MAP kinase (MAPK) pathway inhibitor PD98059 significantly reduced the survival of DA neurons when applied alone in the absence of added growth factors. Application of GDNF plus BDNF, or db-cAMP significantly protected the DA neurons from the deleterious effects on survival of either 20 muM H89 or 20 muM PD98059. The results suggest that BDNF, GDNF, and cAMP produce convergent signals to activate PKA and MAPK pathways which are involved in the survival of postnatal mesencephalic DA neurons in vitro. Published by Elsevier Science (USA).
引用
收藏
页码:32 / 45
页数:14
相关论文
共 77 条
[1]   GDNF family neurotrophic factor signaling: Four masters, one servant? [J].
Airaksinen, MS ;
Titievsky, A ;
Saarma, M .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1999, 13 (05) :313-325
[2]   Neuroprotective strategies for basal ganglia degeneration: Parkinson's and Huntington's diseases [J].
Alexi, T ;
Borlongan, CV ;
Faull, RLM ;
Williams, CE ;
Clark, RG ;
Gluckman, PD ;
Hughes, PE .
PROGRESS IN NEUROBIOLOGY, 2000, 60 (05) :409-470
[3]   The GDNF family ligands and receptors - implications for neural development [J].
Baloh, RH ;
Enomoto, H ;
Johnson, EM ;
Milbrandt, J .
CURRENT OPINION IN NEUROBIOLOGY, 2000, 10 (01) :103-110
[4]   MESENCEPHALIC DOPAMINERGIC-NEURONS PROTECTED BY GDNF FROM AXOTOMY-INDUCED DEGENERATION IN THE ADULT BRAIN [J].
BECK, KD ;
VALVERDE, J ;
ALEXI, T ;
POULSEN, K ;
MOFFAT, B ;
VANDLEN, RA ;
ROSENTHAL, A ;
HEFTI, F .
NATURE, 1995, 373 (6512) :339-341
[5]  
BERRIDGE MV, 1993, EXP HEMATOL, V21, P269
[6]   Studies on neuroprotective and regenerative effects of GDNF in a partial lesion model of Parkinson's disease [J].
Bjorklund, A ;
Rosenblad, C ;
Winkler, C ;
Kirik, D .
NEUROBIOLOGY OF DISEASE, 1997, 4 (3-4) :186-200
[7]   Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms [J].
Bonni, A ;
Brunet, A ;
West, AE ;
Datta, SR ;
Takasu, MA ;
Greenberg, ME .
SCIENCE, 1999, 286 (5443) :1358-1362
[8]   Crosstalk between protein kinase A and growth factor receptor signaling pathways in arterial smooth muscle [J].
Bornfeldt, KE ;
Krebs, EG .
CELLULAR SIGNALLING, 1999, 11 (07) :465-477
[9]   GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR SUPPORTS SURVIVAL OF INJURED MIDBRAIN DOPAMINERGIC-NEURONS [J].
BOWENKAMP, KE ;
HOFFMAN, AF ;
GERHARDT, GA ;
HENRY, MA ;
BIDDLE, PT ;
HOFFER, BJ ;
GRANHOLM, ACE .
JOURNAL OF COMPARATIVE NEUROLOGY, 1995, 355 (04) :479-489
[10]   cAMP included during cell suspension preparation improves survival of dopaminergic neurons in vitro [J].
Branton, RL ;
Love, RM ;
Clarke, DJ .
NEUROREPORT, 1998, 9 (14) :3223-3227