A Role for Phosphodiesterase 11A (PDE11A) in the Formation of Social Memories and the Stabilization of Mood.

摘要: The most recently discovered 3′,5′-cyclic nucleotide phosphodiesterase family is the Phosphodiesterase 11 (PDE11) family, which encoded by a single gene PDE11A. PDE11A dual-specific PDE, breaking down both cAMP and cGMP. There are four splice variants (PDE11A1-4) with distinct tissue expression profiles unique N-terminal regulatory regions, suggesting that each isoform could be individually targeted small molecule or biologic. PDE11A4 expressed in brain found hippocampal formation of humans rodents. Studies rodents show mRNA is, fact, restricted to (CA1, possibly CA2, subiculum, adjacently connected amygdalohippocampal area). Within rodents, protein neurons but not astrocytes, distribution across nuclear, cytoplasmic, membrane compartments. This subcellular localization altered response social experience mouse, vitro studies compartmentalization controlled, at least part, homodimerization phosphorylation. dramatically increases hippocampus age rodent hippocampus, from early postnatal life late aging, function may evolve lifespan. Interestingly, shows three tenfold enrichment ventral (VHIPP; a.k.a. anterior primates) versus dorsal (DHIPP). Consistent this VHIPP, knockout mice regulates memories stabilization mood critical mechanism feeds back modify subsequent behaviors. likely controls behavior regulating glutamatergic, oxytocin, cytokine signaling, as well translation. Given its relatively selective effects on behavior, represent novel therapeutic target for neuropsychiatric, neurodevelopmental, age-related disorders. Therapeutically targeting way selectively restore aberrant cyclic signaling while leaving rest periphery untouched, thus, relieving deficits avoiding unwanted side effects.