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.

Automated summary

New research has found that integrin-alpha V and integrin-beta 5 show different expression levels in human brain tissues across various age groups, while GFRAL protein is less expressed in the hippocampus and cortex. These findings suggest a potentially larger impact of irisin on the developing brain and implications for Zika virus infection in infants and young children.