ALZHEIMERS RESEARCH PROJECT - Exploring neuron-microglia-astrocyte-oligodendrocyte interactions during aging using primary cultures and brain-mimicking and age-relevant organoid models

National Institute On Aging

Investigators

Abstract

In the past year, we have successfully isolated and established culture conditions for neurons (N), microglia (M), astrocytes (A), and oligodendrocytes (O) from young and old mice brains. Our preliminary findings reveal that the primary cultures preserve age-associated molecular markers. We found increased Galectin-3 (LGALS3) staining in microglia from old mouse brains. LGALS3 has been recognized as a key regulator of microglial activation and neuroinflammation, interacting with pattern recognition receptors to modulate microglial responses under pathological conditions. This prompted us to interrogate in greater detail LGALS3's function using our 2D and 3D NMAO models. We have done metabolic profiling, and RNA-seq (with LGALS3 overexpression and knockdown) of young and old microglia. We are currently testing functional consequences of LGALS3 manipulation in co-culture models.