QUANTITATIVE ANALYSIS OF MICROGLIAL CELLS IN THE DEGENERATING CEREBELLUM OF THE STAGGERER (RORA^sg/sg) MUTANT MOUSE

Abstract

Elevated levels of pro-inflammatory cytokines, such as IL-1β and IL-6, have been detected in the cerebellum of Rora^sg/sg mice during the first postnatal month of neurodegenerative process. This suggests the existence of a microglial reaction in the context of an inflammatory process that would be triggered by the massive neuronal loss. To test this hypothesis, we qualitatively and quantitatively studied the microglial cell population using lectin and nucleosidic diphosphatase labeling of the cerebellum of 30-day-old mice. The massive neuronal loss induces a 11.7-fold smaller size of the Rora^sg/sg cerebellum compared to wild-types. We showed that the Rora^sg/sg microglia population is exclusively composed of cells displaying the characteristic morphology of activated cells, with enlarged, heavily stained cell bodies and few thick processes, in contrast to microglial cells in the wild-type. The density of microglia is 2.7-fold higher in Rora^sg/sg than wild-type mice (22444±5011 cells/mm³ versus 8158±1584 cells/mm³), although the absolute number is 4-fold smaller. These results show that neurodegeneration in the Rora^sg/sg cerebellum leads to persistance of microglial activation while in wild-type it disappears around P10.

Keywords:

• Rora
• CNS
• Neurodegeneration
• Inflammation