Inhibitors of phosphodiesterase-4 (PDE4) have beneficial effects on memory in preclinical and clinical studies. Development of these drugs has stalled due to dose-limiting side effects of nausea and emesis. While use of subtype-selective inhibitors (i.e., for PDE4A, B, or D) could overcome this issue, conservation of the catalytic region, to which classical inhibitors bind, limits this approach. The present study examined the effects of BPN14770, an allosteric inhibitor of PDE4D, which binds to a primate-specific, N-terminal region. In mice engineered to express PDE4D with this primate-specific sequence, BPN14770 was 100-fold more potent for improving memory than in wild-type mice; meanwhile, it exhibited low potency in a mouse surrogate model for emesis. BPN14770 also antagonized the amnesic effects of scopolamine, increased cAMP signaling in brain, and increased BDNF and markers of neuronal plasticity associated with memory. These data establish a relationship between PDE4D target engagement and effects on memory for BPN14770 and suggest clinical potential for PDE4D-selective inhibitors.

The term gut health is currently becoming more important for domestic animals including poultry. Gut health refers to the fundamental organ system which covers multiple positive functions like effective digestion, stabilizing intestinal microbiota, gut pH and modulation of effective immune response. Gut health depends on proper balance of microbial population. A wide range of feed and pathogen associated factors influence this balance, and adversely affect the animal health status and production performance. Antibiotic stimulators have been used in farm animals to achieve maximum production. But drug resistance and residual effects of antibiotics in animal products (milk, meat and egg etc.) have raised serious issues in human life. Therefore, The European Union (EU) has strictly banned the application of antibiotic stimulators in livestock nutrition in several others countries including China. As a result, an alternative to antibiotic growth promoters are required to support the profitable and sustainable animal production system. Probiotics as nutraceuticals has been categorized as an alternative natural feed supplement for commercial utilization. Such products have been recognized as safe feed additives in animal industry. Very few studies have comparatively described the effect of probiotics on gut health of domestic animals. Therefore, the aim of this review is not only to explore the beneficial effects of probiotics in improving gut health of domestic animals as an alternative to antibiotic growth promoters, but also to evaluate the probiotics associated health and risk factors, and to provide comprehensive scientific information for researchers, scientists and commercial producers.