PPAR and functional foods: Rationale for natural neurosteroid-based interventions for postpartum depression

Allopregnanolone, a GABAergic neurosteroid and progesterone derivative, was recently approved by the Food and Drug Administration for the treatment of postpartum depression (PPD). Several mechanisms appear to be involved in the pathogenesis of PPD, including neuroendocrine dysfunction, neuroinflammation, neurotransmitter alterations, genetic and epigenetic modifications. Recent evidence highlights the higher risk for incidence of PPD in mothers exposed to unhealthy diets that negatively impact the microbiome composition and increase inflammation, all effects that are strongly correlated with mood disorders. Conversely, healthy diets have consistently been reported to decrease the risk of peripartum depression and to protect the body and brain against low-grade systemic chronic inflammation. Several bioactive micronutrients found in the so-called functional foods have been shown to play a relevant role in preventing neuroinflammation and depression, such as vitamins, minerals, omega-3 fatty acids and flavonoids. An intriguing molecular substrate linking functional foods with improvement of mood disorders may be represented by the peroxisome-proliferator activated receptor (PPAR) pathway, which can regulate allopregnanolone biosynthesis and brain-derived neurotropic factor (BDNF) and thereby may reduce inflammation and elevate mood. Herein, we discuss the potential connection between functional foods and PPAR and their role in preventing neuroinflammation and symptoms of PPD through neurosteroid regulation. We suggest that healthy diets by targeting the PPAR-neurosteroid axis and thereby decreasing inflammation may offer a suitable functional strategy to prevent and safely alleviate mood symptoms during the perinatal period.