MaKenna Cealie - PhD Candidate, Neuroscience Graduate Program
Fetal alcohol spectrum disorders (FASD), caused by prenatal alcohol exposure, are the most common cause of non-heritable, preventable mental disability and have no known cure. Physical, cognitive, and behavioral deficits have been reported in FASD, including impairments related to the cerebellum. To elucidate the mechanisms of FASD, we examined microglia, the immune cells of the central nervous system, as well as Purkinje cells, the sole output of the cerebellar cortex, which are both impacted by developmental ethanol exposure. Microglia are dynamic cells and shape neuronal circuit development and connectivity in the cerebellum. However, how cerebellar microglia dynamics and their interactions with neurons are affected by early life exposure to ethanol is unknown. We explored the impact of a third-trimester equivalent binge-level ethanol exposure on cerebellar microglia and microglia-Purkinje cell interactions in adolescent and young adult mice.
We subcutaneously injected Ai9+/-/C3xcr1G/+/L7cre mice with 5.0 g/kg/day of either ethanol or saline from postnatal (P) days 4-9. Mice were then aged to adolescence (P28) and cranial windows were implanted above the cerebellum to allow for two-photon in vivo imaging in both adolescence and young adulthood (P60). We found that in vivo cerebellar microglia dynamics, microglia morphology, and microglia-Purkinje cell interactions were largely unaffected by developmental ethanol exposure in both adolescence and young adulthood. We also examined if a “second-hit” laser ablation injury in young adulthood would uncover differences, but found no changes in cerebellar microglia injury response between ethanol- and saline-dosed animals. We collected the young adults’ brains for confocal imaging to examine a larger number of microglia and Purkinje cells. Microglia density, morphology, and interactions with Purkinje cells were largely unaltered by developmental ethanol exposure. However, Purkinje cell linear frequency was significantly decreased in ethanol-dosed mice.
Overall, we found that cerebellar microglia in adolescent and young adult mice were largely unaffected by developmental ethanol exposure, but Purkinje cells appeared to be more susceptible to its effects. Our work suggests that microglia may return to homeostasis later in life after an early life insult. This work is important to narrow down the mechanisms leading to FASD so future therapies can be developed.
May 13, 2024 @ 11:00 a.m.
Medical Center | Lower Adolph Aud. (1-7619)
Host: Advisor: Ania Majewska, PhD