Basic Science and Pathogenesis.

Background: Neuroinflammation is a key component of Alzheimer's Disease (AD) pathology. Triggering receptor expressed on myeloid cells 2 (TREM2) is crucial to microglial involvement in AD, mediating trem2-dependent activation and Disease-Associated Microglia (DAM) polarization. However, GWAS revealed that loss-of-function mutations of its encoding gene are an important risk factor for AD.

Sex-specific effects of the histone variant H2A.Z on fear memory, stress-enhanced fear learning and hypersensitivity to pain.

Emerging evidence suggests that histone variants are novel epigenetic regulators of memory, whereby histone H2A.Z suppresses fear memory. However, it is not clear if altered fear memory can also modify risk for PTSD, and whether these effects differ in males and females.

Blocking H2A.Z Incorporation via Tip60 Inhibition Promotes Systems Consolidation of Fear Memory in Mice.

Memory formation is a protracted process that initially involves the hippocampus and becomes increasingly dependent on the cortex over time, but the mechanisms of this transfer are unclear. We recently showed that hippocampal depletion of the histone variant H2A.Z enhances both recent and remote memories, but the use of virally mediated depletion reduced H2A.