PACAP interactions in the mouse brain: Implications for behavioral and other disorders

As an activator of adenylate cyclase, the neuropeptide Pituitary Adenylate Cyclase Activating Peptide (PACAP) impacts levels of cyclic AMP, a key second messenger available in brain cells. PACAP is involved in certain adult behaviors. To elucidate PACAP interactions, a compendium of microarrays representing mRNA expression in the adult mouse whole brain was pooled from the Phenogen database for analysis. A regulatory network was computed based on mutual information between gene pairs using gene expression data across the compendium. Clusters among genes directly linked to PACAP, and probable interactions between corresponding proteins were computed. Database “experts” affirmed some of the inferred relationships. The findings suggest ADCY7 is probably the adenylate cyclase isoform most relevant to PACAP's action. They also support intervening roles for kinases including GSK3B, PI 3-kinase, SGK3 and AMPK. Other high-confidence interactions are hypothesized for future testing. This new information has implications for certain behavioral and other disorders.

► We explore Pituitary Adenylate Cyclase Activating Peptide (PACAP) interactions.
► Various computer algorithms and mouse whole brain gene expression data were used.
► Known PACAP interactions such as with ADCY7, GSK3B and PI 3-kinase were affirmed.
► Novel PACAP interactions include those with ANKRD6, BRAF, GULP1, PRKAA1, RELA, SGK3.
► This new information has implications including for certain behavioral disorders.