Temporal relationship between aquaporin-4 and glial fibrillary acidic protein in cerebellum of neonate and adult rats administered a BBB disrupting spider venom

Abstract

Two astrocyte markers, the glial water channel aquaporin-4 (AQP4) and the glial fibrillary acidic protein (GFAP), have been implicated in several physiological and pathological conditions in the central nervous system (CNS) as well as in blood–brain barrier breakdown (BBBb). By color segmentation the immunoreactivity of both proteins, we demonstrate that the expression of AQP4 and GFAP was increased in the cerebellum of neonate (14-day-old, P14) and adult (8-week-old) rats administered Phoneutria nigriventer spider venom (PNV) known to cause perivascular edema, BBBb and convulsion. In the cerebellum's gray matter, PNV produced a major response, especially in the granular layer. Parallel increases in AQP4 and GFAP expression occurred 24 h after envenomation in the white matter of P14 and in the molecular layer of adults, as well as in the granular layer 2 h after envenomation. In the Purkinje layer there was a tendency of increased AQP4, for both, neonates (5 h), and adults (2 and 24 h). Moreover, PNV also provoked nonparallel upregulation of both markers with prevalence of upregulation of AQP 4 for P14 rats, and GFAP for adults. The major expression of both proteins was in the gray matter. The data indicates a venom effect in water/electrolyte balance in the cerebellum and the participation of AQP4 in these effects. Age-related and time-related regional differences probably reflect specificity in AQP4 distribution in different astrocytic membrane domains as well as its participation in K+ buffering and neural activity. This study is the first to associate astrocytic AQP4 expression and reactive gliosis in a model of BBB permeability promoted by P. nigriventer venom. Our data provide compelling evidence that AQP4 expression was increased in the cerebellum of rats administered PNV.