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APP knockout attenuates microglial activation and enhances neuron survival in substantia nigra compacta after axotomy
Author(s) -
De Giorgio Lorraine A.,
Shimizu Yoshinori,
Chun Hong S.,
Cho ByungPil,
Sugama Shuei,
Joh Tong H.,
Volpe Bruce T.
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10052
Subject(s) - pars compacta , substantia nigra , axotomy , medial forebrain bundle , microglia , neuroscience , biology , neurodegeneration , dopaminergic , pathology , dopamine , medicine , central nervous system , inflammation , immunology , disease
Focal microglial activation and progressive dopaminergic neurodegeneration in substantia nigra compacta (SNc) have characterized Parkinson's disease (PD). We have hypothesized that the microglial response may be provoked by molecular signals from chronically stressed SNc neurons. To test whether amyloid precursor protein (APP) could serve as such a signal, we evaluated microglial activation in SN after unilateral transection of the medial forebrain bundle (MFB) in mice either wild‐type (WT) or null (KO) for APP. WT and KO mice displayed comparable microglial response at the MFB transection site. In WT mice microglial activation was first apparent in the ipsilateral SN at 3 days postlesion (dpl), marked by morphological change and increased isolectin immunoreactivity. The microglial response intensified at 7 dpl and persisted in the medial nigra through 14 dpl. In contrast, in KO mice activated microglia appeared predominantly at 7 dpl, with little activation at 3 dpl and none at 14 dpl. Neuron number in affected WT SNc at 14 dpl was significantly reduced compared with loss in affected KO SNc. The delayed and limited local microglial activation and increased neuron survival in response to distal axotomy of SNc neurons in APP KO mice are consistent with the important role APP in neuronal stress responses in vivo. GLIA 38:174–178, 2002. © 2002 Wiley‐Liss, Inc.