Neuroimmune signaling is increasingly implicated in alcohol use disorder (AUD). Microglia, the brain's resident immune cells, signal in part through the adaptor protein myeloid differentiation primary response 88 (MyD88), a key mediator of innate immune responses. Here, we investigated whether microglial-specific MyD88 signaling regulates voluntary alcohol consumption in adulthood, as whole-body loss of MyD88 was previously shown to increase drinking. We further determined if alcohol altered parvalbumin-expressing interneurons (PVIs) and microglia within the pre-frontal cortex, based on our previously described role for MyD88 signaling on perineuronal net (PNN) deposition on PVIs in several brain regions, and the well characterized role of inhibitory signaling in alcohol use disorders. Loss of microglial-MyD88 had minimal effects on voluntary alcohol intake and anxiety-like behaviors. Alcohol exposure did not modify observed MyD88-dependent changes in PVIs/PNNs, despite altering microglial morphology in the male prefrontal cortex independent of genotype. The addition of an early life endotoxin challenge was sufficient to induce an increase in adult alcohol consumption in both MyD88-deficient and control males. However, injection of saline alone also induced an increase in adult drinking in MyD88-deficient males. These findings suggest that microglial-MyD88 signaling does not strongly regulate alcohol intake under baseline conditions in a one-bottle, voluntary binge-drinking paradigm, however there may be a role for microglial-MyD88 signaling in modulating the impact of developmental environmental contexts, such as stress, in later-life male drinking behavior. This work highlights the importance of developmental context, such as stress or inflammatory history, in understanding underlying microglia signaling mechanisms in conferring AUD risk.
Dziabis, J. E., Rogers, N., Horvath, B. L., Patton, M., Jonathan, I. O., Freeman, E. J., Sun, W., Moulden, J., Zhang, G., Bilbo, S.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 2
- Comments 0