Anxiety-like behavior in mice lacking a Parkinson's disease risk factor, BST1/CD157

Haruhiro Higashida and Olga Lopatina

Research Centre for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan

CD157, also known as bone marrow stromal cell antigen-1, is a glycosylphosphatidylinositol-anchored ADP-ribosyl cyclase that supports the survival and function of B-lymphocytes and hematopoietic or intestinal stem cells. Although CD157 (BST1) has been reported to be a risk locus in Parkinson's disease, little is known about the neuronal function of CD157. Here, we show that knockout (CD157-/-) mice show no apparent motor dysfunction. The CD157-/- mice have a higher level of anxiety in the novel environment, as demonstrated by a preference to be near a protective wall rather than exposed to danger in the open field and lower sociability to the novel non-social and social targets. This anxiety-related behavior was confirmed using the light and dark chamber test. The transition from the light to dark arena was significantly different. The CD157-/- mice entered the dark chamber with an average frequency of 2.2 ± 0.4 times during a 10-min test, while the CD157+/+ mice entered at a frequency of 8.6 ± 2.4 times during the same time span (n = 8, P < 0.01). While in the light zone, the CD157-/- mice moved significantly more slowly than the CD157+/+ mice (n = 8, P < 0.05). CD157-/- adult male mice also exhibited social avoidance and depression-like behavior compared with wild-type mice. These behaviors were rescued through treatment with anti-anxiety and anti-depression drugs or oxytocin. These results demonstrate for the first time that BST1/CD157 plays a role in the nervous system as a neuro-entero-immunological regulator and suggest that CD157 gene disruption results in emotion-related phenotypes of Parkinson's disease in mice.