Phosphodiesterase 8 (PDE8): Distribution and Cellular Expression and Association with Alzheimer's Disease.

ABSTRACT

Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.