Beta amyloid 1–42‐induced depressive‐like behavior and decreases in adult neurogenesis are mediated by the phosphodiesderase‐4D (PDE4D) enzyme

Abstract

Studies have shown that depression may be either a risk factor for Alzheimer's disease (AD) or an early symptom of AD. However, it is not known whether beta amyloid peptide 1–42 (Abeta42), which is mainly responsible for memory loss in AD, plays a role in depression associated with AD. Phosphodiesterase‐4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP, is involved in the mediation of antidepressant activity and memory. We examined the effects of Abeta42 on behavior in the forced‐swim and tail‐suspension tests in mice. Abeta42 (0.1, 0.4, and 1.6 μg/side), microinfused into bilateral dentate gyri of the mouse hippocampus, increased immobility in a dose‐dependent manner in both tests; it also decreased hippocampal neurogenesis, which is associated with depression. Interestingly, Abeta42 (0.4 μg/side)‐induced depressive‐like effects and decreases in neurogenesis were reversed by deficiency of PDE4D, one of the four PDE4 subtypes. These results suggest that Abeta42 may be an important mediator for depression in AD; disruption of PDE4D appears to be an effective approach to treatment of AD‐associated depression.