ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo

被引：122

作者：

Barcia, Carlos ^{[1
]}

Maria Ros, Carmen ^{[1
]}

Annese, Valentina ^{[1
]}

Carrillo-de Sauvage, Maria Angeles ^{[1
]}

Ros-Bernal, Francisco ^{[1
]}

Gomez, Aurora ^{[1
]}

Enrique Yuste, Jose ^{[1
]}

Maria Campuzano, Carmen

de Pablos, Vicente ^{[1
]}

Fernandez-Villalba, Emiliano ^{[1
]}

Trinidad Herrero, Maria ^{[1
]}

机构：

[1] Univ Murcia, Ctr Invest Biomed Red Enfermedade Neurodegenerat, Sch Med, E-30071 Murcia, Spain

来源：

SCIENTIFIC REPORTS | 2012年 / 2卷

关键词：

ACTIN STRESS FIBERS; SUBSTANTIA-NIGRA; MOUSE MODEL; PARKINSONS; ACTIVATION; RHO; RECEPTOR; DEGRADATION; DISEASE; GTPASES;

D O I：

10.1038/srep00809

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The role of microglial motility in the context of adult neurodegeneration is poorly understood. In the present work, we investigated the microanatomical details of microglia-neuron interactions in an experimental mouse model of Parkinson's disease following the intraperitoneal injection of MPTP. The specific intoxication of dopaminergic neurons induces the cellular polarization of microglia, leading to the formation of body-to-body neuron-glia contacts, called gliapses, which precede neuron elimination. Inhibiting ROCK/Cdc42-mediated microglial motility in vivo blocks the activating features of microglia, such as increased cell size and number of filopodia and diminishes their phagocyting/secreting domains, as the reduction of the Golgi apparatus and the number of microglia-neuron contacts has shown. High-resolution confocal images and three-dimensional rendering demonstrate that microglia engulf entire neurons at one-to-one ratio, and the microglial cell body participates in the formation of the phagocytic cup, engulfing and eliminating neurons in areas of dopaminergic degeneration in adult mammals.

引用

页数：13

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