AUTHOR=Carriba Paulina , Wyatt Sean , Davies Alun M. 

TITLE=CD40L Reverse Signaling Influences Dendrite Spine Morphology and Expression of PSD-95 and Rho Small GTPases

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00254

DOI=10.3389/fcell.2020.00254

ISSN=2296-634X

ABSTRACT=<p>CD40-activated CD40L reverse signaling is a major physiological regulator of neural process growth from many kinds of developing neurons. Here we have investigated whether CD40L-reverse signaling also influences dendrite spine number and morphology in striatal medium spiny neurons (MSNs). Golgi preparations revealed no differences in the spine density, but because the dendrite arbors of MSNs were larger and branched in <italic>Cd40</italic><sup>–/–</sup> mice, the total number of spines was greater in <italic>Cd40</italic><sup>–/–</sup> mice. We also detected more mature spines compared with wild-type littermates. Western blot revealed that MSN cultures from <italic>Cd40</italic><sup>–/–</sup> mice had significantly less PSD-95 and there were changes in RhoA/B/C and Cdc42. Immunocytochemistry revealed that PSD-95 was clustered in spines in <italic>Cd40</italic><sup>–/–</sup> neurons compared with more diffuse labeling in <italic>Cd40</italic><sup>+/+</sup> neurons. Activation of CD40L-reverse signaling with CD40-Fc prevented the changes observed in <italic>Cd40</italic><sup>–/–</sup> cultures. Our findings suggest that CD40L-reverse signaling influences dendrite spine morphology and related protein expression and distribution.</p>