Multiple Sclerosis. The role of microglia in regulating axon initial segment integrity in health and disease.

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Presentation transcript:

The role of microglia in regulating axon initial segment integrity in health and disease

Multiple Sclerosis

The axon initial segment (AIS) Demyelination vs. AIS Inflammation

Microglia Surveying (non- reactive) Reactive

Microglia vs. AIS In healthy subject (Baalman et al. 2015) In EAE//MS (Clark et al. 2016) In brain injury (TBI)

Focus Do surveying microglia support the AIS? Do reactive microglia damage the AIS?

Experiment Healthy Brain Injury (TBI) Remove microglia Examine consequence to AIS: length, number, function Healthy Surveying microglia may support AIS → no surveying microglia → decrease health AIS? Brain Injury (TBI) Microglial activation follows TBI Remove microglia → no reactive microglia → reduce damage to AIS?

Removal microglia (Cre)/LoxP ablation colony stimulating factor 1 receptor (CSF1R) “floxed” mouse Cre-ER mouse confocal microscopy//IBA-1 immunostaining

Method TBI Controlled cortical impact

Groups 8 groups 3 days and 7 days post microglia knockout Microglia knockout and TBI vs. No microglia knockout and TBI Microglia knockout and no TBI vs. No microglia knockout and no TBI 3 days and 7 days post microglia knockout

AIS analysis length and number Function (EP)

Discussion Healthy (no TBI) mice TBI mice Desired result Surveying microglia support AIS TBI mice Small population surveying microglia supports Small population reactive microglia disrupts Desired result Remove microglia in health → AIS disruption Remove microglia in TBI → attenuate AIS disruption