Cannabinoid receptor expression and phosphorylation are differentially regulated between male and female cerebellum and brain stem after repeated stress: implication for XXXX and drug abuse.

@entity35 @entity148 @entity1005
Recent study demonstrated a close relationship between cerebellum atrophy and symptom severity of pediatric maltreatment-related @entity1005 ( @entity1005 ). It has also been known that females are more vulnerable than males in developing @entity148 after exposure to traumatic stress. The mechanisms are unknown. Because cannabinoid receptors (CB    and CB   ) are neuroprotective and highly expressed in the cerebellum, we investigated cerebellar CB expression in stressed @entity35 . Young male and female @entity35 were given 40 unpredictable electric tail-shocks for 2h daily on 3 consecutive days. CB    and CB    mRNA and protein levels in @entity35 cerebellum and brain stem were determined using quantitative real-time PCR and Western blot, respectively. Two-way ANOVA revealed significant gender and stress effects on cerebellar CB    mRNA expression, with females and non-stressed @entity35 exhibiting higher CB    mRNA levels than the males (3 fold, p<0.01) and stressed @entity35 (30%, p<0.01), respectively. CB    and CB    mRNA levels in brain stem were also greater in female @entity35 than males (p<0.01, p<0.05, respectively). Repeated stress increased the level of phosphorylated CB    receptors, the inactivated CB   , in @entity35 cerebellum (p<0.01), particularly in female @entity35 as revealed by the significant gender   stress interaction. Thus, repeated severe stress caused greater CB    mRNA suppression and CB    receptor phosphorylation in female cerebellum that could lead to increased susceptibility to stress-related @entity148 including @entity1005 .
