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Modification of microglia function protects from lesion‐induced neuronal alterations and promotes sprouting in the hippocampus
Author(s) -
Eyüpoglu Ilker Y.,
Bechmann Ingo,
Nitsch Robert
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0825fje
Subject(s) - microglia , neuroscience , reinnervation , hippocampus , entorhinal cortex , hippocampal formation , lesion , denervation , biology , chemistry , pathology , anatomy , inflammation , medicine , immunology
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 1β up‐regulation, which is attenuated by the immuno‐modulator transforming growth factor β1, whereas tumor necrosis factor α 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.