Transmembrane adenylyl cyclases (Adcy) are involved in the regulation of multiple brain processes such as synaptic plasticity, learning and memory. They synthesize intracellular cyclic adenosine monophosphate (cAMP) following activation by G-protein coupled receptors. We examined the neuroanatomical distribution of the nine Adcy isoforms in rat and mouse brain by in situ hybridization, as well as their location in glutamatergic, GABAergic and cholinergic neurons in several mouse brain areas by double in situ hybridization. The Adcys are widely distributed throughout the brain in both rat and mouse, being especially abundant in cortex, hippocampus, thalamic nuclei, the olfactory system and the granular layer of the cerebellum. Double-labeling experiments showed that Adcy isoforms are differently expressed in glutamatergic, GABAergic and cholinergic neuronal cell populations. We report the neuroanatomical distribution of the nine known Adcy isoforms in rat and mouse brain and their cellular localization.

Many inflammatory processes involve cAMP. Pharmacological manipulation of cAMP levels using specific phosphodiesterase (PDE) inhibitors provokes an antiinflammatory response. The aim of this study was to investigate changes in the pattern and levels of expression of mRNAs coding for the cAMP‐specific PDE4 family and subfamilies in mouse brain during the immediate acute immune response provoked by an intraperitoneal injection of lipopolysaccharide (LPS). PDE4B, and furthermore the splice variants PDE4B2 and PDE4B3, were the only mRNAs that showed altered expression. Whereas PDE4B2 presented increased expression at both 3 and 8 hr postinjection, PDE4B3 mRNA showed decreased expression that reached a minimum 8 hr postinjection. PDE4B2 mRNA upregulation was observed mainly in endothelial and macrophage/neutrophil cell populations in the leptomeninges, and the downregulation of PDE4B3 was observed mainly in oligodendrocytes throughout the brain. Our results clearly illustrate the distinctive anatomical distribution and cellular localization of the PDE4Bs during neuroinflammation and emphasize the importance of PDE4B splice‐variant‐specific inhibitors as therapeutic tools. © 2011 Wiley‐Liss, Inc.