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

Travis C Jackson,Kiersten Gorse,Patrick M Kochanek,Jeremy R Herrmann

doi:10.1007/s12035-020-02250-4

Abstract

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-αV/β5 heterodimers while GDF-15 binds to the orphan receptor glial cell-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL). In addition, integrin-αV/β5 was just identified as the key receptor mediating Zika virus infection in the CNS. We measured integrin-αV, integrin-β5, 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-αV was detected at all ages in the prefrontal cortex with levels greatest in adults. Integrin-αV was also detected in the hippocampus in all age groups. In contrast, integrin-β5 was detected in cortex and hippocampus largely restricted to infants. Co-expression of integrin-αV/β5 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.

Highlights

Cold-stress hormones (CSHs) are broadly defined as hormones that increase their production and/or secretion in response to cold-stressors [1]
We previously demonstrated that polyvinylidene fluoride or polyvinylidene difluoride (PVDF) membranes robustly alter the fidelity of antibodies to detect cold-shock proteins (CSPs) by Western blot analysis [35]
To substantiate that instances in which CSPs/ CSH receptors are only found in infants were not caused by extraneous factors like differences in sample quality, we measured myelin basic protein (MBP)

Summary

Introduction

Cold-stress hormones (CSHs) are broadly defined as hormones that increase their production and/or secretion in response to cold-stressors [1]. Mol Neurobiol (2021) 58:2145–2157 suggest critical importance of defining CSH receptor levels in the human brain at different ages to understand the mechanisms potentially targeted by cerebroprotective cooling in a variety of populations [2, 3]. Those studies may provide additional insights relevant to neurodevelopment and/or other disease processes in humans. To better understand if age influences CNS responses to stimuli that increase irisin levels (such as cold-stress), studies are needed to define the protein levels of irisin receptor components in the developing vs the mature human brain, including in injuryprone brain regions like the hippocampus [15].

GFRAL Cusabio

Experimental Procedures

Results and Discussion

Conclusion

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