Hippocampal and Prefrontal Cortical Brain Tissue Levels of Irisin and GDF15 Receptor Subunits in Children

Cold-stress hormones (CSHs) stimulate thermogenesis and have direct neuroprotective effects on the brain. The obligatory receptor components of two new CSHs (irisin and growth differentiation factor-15 [GDF15]) were recently discovered. Irisin binds integrin-alpha V/beta 5 heterodimers while GDF-15 binds to the orphan receptor glial cell-derived neurotrophic factor (GDNF) family receptor alpha-like (GFRAL). In addition, integrin-alpha V/beta 5 was just identified as the key receptor mediating Zika virus infection in the CNS. We measured integrin-alpha V, integrin-beta 5, and GFRAL protein levels across 78 high-quality human male/female brain tissues in infants, toddlers, preschoolers, adolescent, and adults-providing the most robust analysis to date on their levels in the human cortex and hippocampus. We report that integrin-alpha V was detected at all ages in the prefrontal cortex with levels greatest in adults. Integrin-alpha V was also detected in the hippocampus in all age groups. In contrast, integrin-beta 5 was detected in cortex and hippocampus largely restricted to infants. Co-expression of integrin-alpha V/beta 5 in the human infant hippocampus and cortex suggests the possibility that irisin has a more robust effect on the developing vs. the adult brain and may have implications for Zika virus infection in infants and young children.