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

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 Cd40(–/–) mice, the total number of spines was greater in Cd40(–/–) mice. We also detected more mature spines compared with wild-type littermates. Western blot revealed that MSN cultures from Cd40(–/–) 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 Cd40(–/–) neurons compared with more diffuse labeling in Cd40(+/+) neurons. Activation of CD40L-reverse signaling with CD40-Fc prevented the changes observed in Cd40(–/–) cultures. Our findings suggest that CD40L-reverse signaling influences dendrite spine morphology and related protein expression and distribution.