An immunohistochemical, enzymatic, and behavioral study of CD157/BST-1 as a neuroregulator

Haruhiro Higashida, Mingkun Liang, Toru Yoshihara, Shirin Akther, Azam Fakhrul, Cherepanov Stanislav, Tae-Sik Nam, Uh-Hyun Kim, Satoka Kasai, Tomoko Nishimura, Naila Al Mahmuda, Shigeru Yokoyama, Katsuhiko Ishihara, Maria Gerasimenko, Alla Salmina, Jing Zhong, Takahiro Tsuji, Chiharu Tsuji, Olga Lopatina

Recent rodent and human studies provide evidence in support of the fact that CD157, well known as bone marrow stromal cell antigen-1 (BST-1) and a risk factor in Parkinson's disease, also meaningfully acts in the brain as a neuroregulator and affects social behaviors. It has been shown that social behaviors are impaired in CD157 knockout mice without severe motor dysfunction and that CD157/BST1 gene single nucleotide polymorphisms are associated with autism spectrum disorder in humans. However, it is still necessary to determine how this molecule contributes to the brain's physiological and pathophysiological functions. To gain fresh insights about the relationship between the presence of CD157 in the brain and its enzymatic activity, and aberrant social behavior, CD157 knockout mice of various ages were tested. CD157 immunoreactivity colocalized with nestin-positive cells and elements in the ventricular zones in E17 embryos. Brain CD157 mRNA levels were high in neonates but low in adults. Weak but distinct immunoreactivity was detected in several areas in the adult brain, including the amygdala. CD157 has little or no base exchange activity, but some ADP-ribosyl cyclase activity, indicating that CD157 formed cyclic ADP-ribose but much less nicotinic acid adenine dinucleotide phosphate, with both mobilizing Ca(2+) from intracellular Ca(2+) pools. Social avoidance in CD157 knockout mice was rescued by a single intraperitoneal injection of oxytocin. CD157 may play a role in the embryonic and adult nervous systems. The functional features of CD157 can be explained in part through the production of cyclic ADP-ribose rather than nicotinic acid adenine dinucleotide phosphate. Further experiments are required to elucidate how the embryonic expression of CD157 in neural stem cells contributes to behaviors in adults or to psychiatric symptoms.