Modification of microglia function protects from lesion-induced neuronal alterations and promotes sprouting in the hippocampus

被引:47
作者
Eyüpoglu, IY [1 ]
Bechmann, I [1 ]
Nitsch, R [1 ]
机构
[1] Humboldt Univ Hosp Charite, Dept Cell & Neurobiol, Inst Anat, D-10098 Berlin, Germany
关键词
parvalbumin; dendritic arborization; reinnervation;
D O I
10.1096/fj.02-0825fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Primary neuronal destruction in the central nervous system triggers rapid changes in glial morphology and function, after which activated glial cells contribute to secondary neuronal changes. Here we show that, after entorhinal cortex lesion, activation of microglia, but not other glial cells, leads to massive secondary dendritic changes of deafferentiated hippocampal neurons. Blocking of microglial activation in vivo reduced this secondary neuronal damage and enhanced regenerative axonal sprouting. In contrast, abolishing astrocytes or oligodendroglia did not result in specific neuronal changes. Furthermore, primary damage leads to an interleukin 1beta upregulation, which is attenuated by the immuno-modulator transforming growth factor beta1, whereas tumor necrosis factor alpha is not affected. Modification of microglial activity following denervation of the hippocampus protects neurons from secondary dendritic alterations and therefore enables their reinnervation. These data render activated microglia a putative therapeutic target during the course of axonal degeneration.
引用
收藏
页码:1110 / +
页数:20
相关论文
共 58 条
[1]  
Amaral David G., 1995, P443
[2]  
Batchelor PE, 1999, J NEUROSCI, V19, P1708
[3]   Identification of phagocytic glial cells after lesion-induced anterograde degeneration using double-fluorescence labeling: Combination of axonal tracing and lectin or immunostaining [J].
Bechmann, I ;
Nitsch, R .
HISTOCHEMISTRY AND CELL BIOLOGY, 1997, 107 (05) :391-397
[4]  
Bechmann I, 1997, GLIA, V20, P145, DOI 10.1002/(SICI)1098-1136(199706)20:2<145::AID-GLIA6>3.0.CO
[5]  
2-8
[6]  
Beyer M, 2000, GLIA, V31, P262, DOI 10.1002/1098-1136(200009)31:3<262::AID-GLIA70>3.0.CO
[7]  
2-2
[8]  
Bhat RV, 1996, J NEUROSCI, V16, P4146
[9]   PROLIFERATION RATE OF OLIGODENDROCYTES IN CULTURE CAN BE INFLUENCED BY EXTRINSIC FACTORS [J].
BOLOGA, L ;
ZGRAGGEN, A ;
HERSCHKOWITZ, N .
DEVELOPMENTAL NEUROSCIENCE, 1984, 6 (01) :26-31
[10]   The transforming growth factor-βs:: Structure, signaling, and roles in nervous system development and functions [J].
Böttner, M ;
Krieglstein, K ;
Unsicker, K .
JOURNAL OF NEUROCHEMISTRY, 2000, 75 (06) :2227-2240