Differential Activation of Microglia in the Substantia Nigra and Lesioned Site Following Medial Forebrain Bundle Transection.
- Author:
Byung Pil CHO
1
;
Dae Yong SONG
;
Jung Cheol PARK
;
Jin Suk LEE
;
Byung Gu PARK
;
Byoung Young CHOI
;
Ho Suck KANG
Author Information
1. Department of Anatomy, Yonsei University Wonju College of Medicine, Wonju, Korea. bpcho@wonju.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Medial forebrain bundle;
Axotomy;
Microglia;
Substantia nigra;
Apoptosis;
Necrosis
- MeSH:
Animals;
Antibodies;
Apoptosis;
Axons;
Axotomy;
Brain;
Carisoprodol;
Cell Death;
Dendrites;
Hand;
Macrophages;
Medial Forebrain Bundle*;
Microglia*;
Necrosis;
Neurons;
Phagocytosis;
Phenotype;
Rats;
Substantia Nigra*
- From:Korean Journal of Anatomy
2004;37(4):317-327
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Medial forebrain bundle (MFB) transmits the nigrostriatal dopaminergic (DA) axons, and previously we reported that transection of the MFB causes apotosis-like neurodegeneration of nigral DA neurons. On the other hand, it is likely to occur necrosis at the lesioned site where MFB is cut, due to direct mechanical transection of the brain tissue. To clarify the pathological dynamics of microglia reacting to the two different types of neuronal cell death, immunophenotypic and morphological features of microglia were compared and analyzed in the substantia nigra (SN) and lesioned site of the MFB axotomized rat brain. OX42 (mouse anti-rat CD 11b; pan-microglia marker), ED1 (mouse anti-rat lysosomal enzyme; phagocytic marker), and OX6 (mouse anti-rat MHC II) were used as primary antibodies for immunohistochemical localization of microglia, ED2 (mouse anti-rat macrophage) for macrophages, and anti-tyrosine hydro-xylase (TH) antibody for DA neurons. Quite numerous activated microglia with strong OX42 immunoreactivity were found in the SN at 1 day post-lesion (dpl), but most of them were ED1-and OX6-negative except only a few which were ED1-positive. This phenomenon was thought to be related with the stage of alert, the first step of microglial activation. It could be presumed that microglial phagocytosis may precede MHC II expression, because ED1-positive microglia appeared from 1 dpl while OX6-positive ones from 3 dpl. Number of activated microglia showing strong ED1, OX6 and OX42 immunoreactivity increased significantly by 7 ~14 dpl, and they specifically stick to various parts of dendrites and somas of TH-immunoreactive neurons of the SN. The phagocytic microglia of the SN maintained ramified form although they retained enlarged soma and shortened, thickened processes. The lesioned site was surrounded by numerous microglia showing strong OX42 and ED1 immunoreactivity as early as 1 dpl, indicating that microglial phagocytosis starts earlier in the lesioned site than in the SN. OX42-positive microglia of the lesioned site were ED2-negative, and showed amoeboid morphology already from 1 dpl. The amoeboid microglia became to be enlarged in their soma size by 3 dpl, and fused each other to form clumps within the necrotic zone by 5 ~7 dpl. The entire necrotic zone was completely filled with microglia of obscure outline with strong OX42 and ED1 immuno-reactivity. However, the majority of amoeboid microglia of the lesioned site were OX6-negative except a few. These results clearly demonstrate that activated microglia reacting to apoptotic neurodegeneration show different pathodynamic characteristics in terms of immunological phenotypes and morphology from those reacting to necrotic, mechanical lesion.
