BDNF, and full length and truncated TrkB expression in the hippocampus of the rat following kainic acid excitotoxic damage.: Evidence of complex time-dependent and cell-specific responses

被引:53
作者
Goutan, E
Martí, E
Ferrer, I
机构
[1] Univ Barcelona, Dept Biol Cellular & Anat Patol, Unitat Neuropatol, Hospitalet de Llobregat 08907, Spain
[2] Univ Barcelona, Dept Biol Cellular & Anat Patol, Lab Neurobiol Cellular & Mol, Hospitalet de Llobregat 08907, Spain
[3] Univ Barcelona, Hosp Princeps Espanya, Dept Biol Cellular & Anat Patol, Serv Anat Patol,Unitat Neuropatol, Hospitalet de Llobregat 08907, Spain
来源
MOLECULAR BRAIN RESEARCH | 1998年 / 59卷 / 02期
关键词
kainic acid; BDNF; full-length TrkB; truncated TrkB; hippocampus;
D O I
10.1016/S0169-328X(98)00156-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Systemic administration of kainic acid (KA) at convulsant doses results in irreversible cell damage and neuron loss in the hilus of the dentate gyrus and in the CA1 area of the hippocampus. This is followed by reactive astrocytosis in these regions, and sprouting of mossy fibers into the molecular layer of the dentate gyrus. Since trophic factors are probably implicated in the cellular responses to the excitotoxic insult, and early induction of BDNF and TrkB mRNAs has been observed following KA injection, the present study examines BDNF, full-length and truncated TrkB protein expression in the hippocampus, as revealed by immunohistochemistry, up to 30 days following KA administration to adult rats. Reduction in BDNF and full-length TrkB immunoreactivity preceding neuron loss is observed in the damaged areas. However, transient increase in BDNF immunoreactivity is observed in surviving CA1 neurons and in granule cells of the dentate gyrus. In contrast, full-length TrkB immunoreactivity progressively increases in the molecular layer of the dentate gyrus up to day 30 following KA administration. A second peak in BDNF immunoreactivity is observed in reactive astrocytes, as revealed with double-labeling immunohistochemistry to BDNF and GFAP, in the plexiform layers of CA1 and, to a lesser degree, in the molecular layer of the dentate gyrus. In addition, strong truncated TrkB immunoreactivity is found in reactive astrocytes, as revealed with double-labeling immunohistochemistry to truncated TrkB and GFAP, in the same regions. These results, in concert with previous observations in the same model of hippocampal damage, suggest that BDNF participates in the early response to excitotoxic damage, and that expression of full-length TrkB at strategic sites in the molecular layer of the dentate gyrus has a role in the regenerative response linked to mossy fiber sprouting. Interestingly, delayed expression of BDNF and truncated TrkB in reactive astrocytes may act as negative regulators of neurite growth in devastated regions, such as the CA1 area, which are impoverished of putative postsynaptic sites. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:154 / 164
页数:11
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