Abstracts

This abstract has been invited to present during the Broadening Representation Inclusion and Diversity by Growing Equity (BRIDGE) poster session

Rationale: The developing brain is uniquely susceptible to seizures. Seizures during the early postnatal period can have deleterious consequences to brain development leading to behavioral outcomes such as deficits in communication, cognition and increased anxiety. However, the mechanisms by which neonatal seizures disrupt neurodevelopment are unclear. Microglia are resident brain immune cells that respond to insults and exhibit important roles in development such as synapse pruning, maturation and function. Synaptic pruning is an important developmental process that has shown to be altered in developmental disorders such as autism spectrum disorder and schizophrenia. The pruning of synapses occurs during development in synapses that are tagged by the complement proteins C1q and C3. These complement proteins are increased in response to status epilepticus (SE) in adult rodents. Thus, we hypothesize that neonatal SE leads to the upregulation of the complement system. This increase in complement signaling can potentially alter synaptic pruning and lead to behavioral deficits later in life. 

Methods: Mice were treated with 2 mg/kg kainic acid intraperitoneally at postnatal day 10 to induce SE. Following SE, hippocampal microglial activation was assessed at 1, 2, 3, 4, and 5 days, 2 weeks and 1 month after SE using flow cytometry to quantify MHCII+ myeloid cells.  Expression of the complement system proteins C1q, C3, and C4 were measured at 1 day, 2 days and 2 weeks after SE by RT-qPCR.

Results: Microglial activation was significantly increased by SE (p < 0.001) with the highest activation occurring at one- and two-days post SE (p < 0.001). Complement system proteins expression was also altered in a time dependent manner. C4 expression was decreased one day after SE, and C3 and C1q expression was increased 2 weeks after SE (p < 0.05).