Brain-blood biomarkers take a walk on the wild side: glial responses to environmental conditions and individual traits in wild frogs

Proteins from brain cells, including Glial fibrillary acidic protein (GFAP), has been tested for diagnostic and prognostic of neurological dysfunctions. Release of GFAP into the blood-stream, may be a consequence of its up-regulation in reactive astrocytes. However, astrocytic-GFAP expression is also increased during brain remodeling after physiological perturbations such as osmotic challenge. The presence and quantification of GFAP in blood circulation have never been investigated in the context of brain responses to environmental variations in wildlife. In a wild amphibian (green frogs, Pelophylax sp.), captured in several ponds with different salinity, GFAP was detected in plasma. Males from more saline ponds exhibited higher plasmatic GFAP levels, independent to their blood osmolality, suggesting that plasmatic GFAP-level reflects cerebral response to osmotic challenge. Plasmatic-GFAP correlated with immune markers (hemoglobin binding proteins, lymphocytes, neutrophils and monocytes), size and body condition, reinforcing its role as a physiological biomarker. We also highlighted that captivity had a significant effect on plasmatic-GFAP levels with sex-specific dynamics, masking the response to a short-term experimental salinity exposure. For the very first time, we show that plasmatic-GFAP levels could be a biomarker of brain plasticity to environmental conditions, physiological traits, and stress responses in wildlife. Significant StatementWe investigated the use of brain Glial fibrillary acidic protein (GFAP), a cytoskeletal protein of astrocytes, that has been associated with brain disorders in clinical studies, as a biomarker of environmental conditions and individual traits in wildlife. In a wild amphibian, plasmatic GFAP-levels were correlated with the salinity of ponds, immune markers and size for males. GFAP-levels were correlated with body condition for both sexes. Interestingly, captivity induced transient increase of plasmatic-GFAP levels, probably due to stress. In our study, we demonstrate that plasmatic-GFAP levels may represent an excellent brain biomarker of its plasticity to environmental conditions, physiological traits, and stress responses in wildlife.