RT Journal Article
SR Electronic
T1 ADAP1/Centaurin-α1 Negatively Regulates Dendritic Spine Function and Memory Formation in the Hippocampus
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0111-20.2020
DO 10.1523/ENEURO.0111-20.2020
VO 8
IS 1
A1 Erzsebet M. Szatmari
A1 Corey Moran
A1 Sarah Cohen
A1 Amanda Jacob
A1 Paula Parra-Bueno
A1 Naomi Kamasawa
A1 Debbie Guerrero-Given
A1 Michael Klein
A1 Robert Stackman, Jr
A1 Ryohei Yasuda
YR 2021
UL http://www.eneuro.org/content/8/1/ENEURO.0111-20.2020.abstract
AB ADAP1/Centaurin-α1 (CentA1) functions as an Arf6 GTPase-activating protein highly enriched in the brain. Previous studies demonstrated the involvement of CentA1 in brain function as a regulator of dendritic differentiation and a potential mediator of Alzheimer’s disease (AD) pathogenesis. To better understand the neurobiological functions of CentA1 signaling in the brain, we developed Centa1 knock-out (KO) mice. The KO animals showed neither brain development nor synaptic ultrastructure deficits in the hippocampus. However, they exhibited significantly higher density and enhanced structural plasticity of dendritic spines in the CA1 region of the hippocampus compared with non-transgenic (NTG) littermates. Moreover, the deletion of Centa1 improved performance in the object-in-place (OIP) spatial memory task. These results suggest that CentA1 functions as a negative regulator of spine density and plasticity, and of hippocampus-dependent memory formation. Thus, CentA1 and its downstream signaling may serve as a potential therapeutic target to prevent memory decline associated with aging and brain disorders.