Acute illness induces systemic inflammation which often spreads into the brain causing neuroinflammation (NI) and hyperexcitability (HE). NI and HE lead to many kinds of cognitive dysfunctions and chronic neurodegeneration, such as Alzheimer's disease (AD). Medications blocking overt brain excitability have alleviated cognitive symptoms in patients with early AD, pointing to HE as a strong candidate for an early etiological hub in multiple cognition-debilitating conditions. Our team is a global leader in research on ion transporters KCC2 and NKCC1, which control the efficacy of GABAergic inhibition. Our novel data shows that KCC2 and NKCC1 both have a major role in the inflammatory HE, and further that the highest levels of NKCC1 protein among brain cells are seen in oligodendrocytes, which react strongly in NI. This project is set to identify the mechanisms by which NKCC1 and KCC2 act during NI to cause HE, aiming for novel therapies for cognitive dysfunctions at early stages of AD.

2023

2027