Research Day

Title

Deafferentation and Direct Injury Cause Different Microglial Response Profiles in the Adult Zebrafish Olfactory Bulb

Document Type

Abstract

Date

2017

Abstract

Brain disease and injury involve the activation of resident and peripheral immune cells to clear damaged neurons. The regenerative nature of the zebrafish olfactory system serves as a useful model for examining the response of immune cells following injury. Microglia are the resident immune cells of the central nervous system that respond to damage by migrating to the site of injury and phagocytizing neuronal debris. Preliminary data suggested that peripheral deafferentation and direct injury to the bulb result in activation of microglia, but the origin and pattern of microglial migration remains unclear. We performed peripheral deafferentation and direct injury to the olfactory bulb in the whole fish and compared it to the isolated brain removed of all afferent input and peripheral influence. The olfactory bulbs of adult zebrafish were damaged by cauterizing the olfactory organ or directly injuring the bulb with a stab wound. Removal of afferent input and peripheral influence was performed by isolating and culturing the brain. Mouse monoclonal 4C4 antibody was used to label microglia. Comparisons of whole fish treatment groups to controls showed a significant increase in activated microglia in the damaged bulb following peripheral deafferentation at 4, 12, 24, 48, and 72h post injury. Amoeboid profiles significantly increased between 1-4h, decreased between 4-12h, increased again at 12-24h, and decreased again at 24-48h. Following direct injury to the bulb, there was a significant increase in activated microglia in the ipsilateral and contralateral bulbs at 1 and 4h after injury. Following 4h after injury, there was a significant decrease in amoeboid profiles, which remained low until 72h. Comparisons of isolated brain treatment groups to controls showed significantly more activated microglia in the olfactory bulbs after 4 and 12h in culture. Isolated brains that received a direct injury showed significant increase in activated microglia after 1, 4, and 12h in culture. Isolated brains that received a direct injury also showed significantly less responsive microglia in the damaged bulb when compared to the direct injury to the bulb in the whole fish at 12h. Peripheral deafferentation and direct injury to the olfactory bulb result in different microglial response profiles and suggest a temporal significance and selective phagocytosis during the resolution of inflammation. Microglia can respond to signals without afferent input or peripheral influence up to a certain time after injury. Further work is required to explore the origin and temporal sequence of the immune cells that respond to injury.

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