Impact of Swiprosin-1/Efhd2 on Adult Hippocampal Neurogenesis

Abstract

Swiprosin-1/Efhd2 (Efhd2) is highly expressed in the CNS during development and in the adult. EFHD2 is regulated by Ca2+ binding, stabilizes F-actin, and promotes neurite extension. Previous studies indicated a dysregulation of EFHD2 in human Alzheimer's disease brains. We hypothesized a detrimental effect of genetic ablation of Efhd2 on hippocampal integrity and specifically investigated adult hippocampal neurogenesis. Efhd2 was expressed throughout adult neuronal development and in mature neurons. We observed a severe reduction of the survival of adult newborn neurons in Efhd2 knockouts, starting at the early neuroblast stage. Spine formation and dendrite growth of newborn neurons were compromised in full Efhd2 knockouts, but not upon cell- autonomous Efhd2 deletion. Together with our finding of severe hippocampal tauopathy in Efhd2 knockout mice, these data connect Efhd2 to impaired synaptic plasticity as present in Alzheimer's disease and identify a role of Efhd2 in neuronal survival and synaptic integration in the adult hippocampus.