title: 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.
authors: Department of Histology and Embryology, Institute of Biology, State University of Campinas (Unicamp), 13 083-970 Campinas, SP, Brazil.
authors: Leila Miguel
authors: LM
authors: Stavale
authors: Edilene Siqueira
authors: ES
authors: Soares
authors: Monique C P
authors: MC
authors: Mendonça
authors: Silvia P
authors: SP
authors: Irazusta
authors: Maria Alice
authors: MA
authors: da Cruz Höfling
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051401:Aquaporin 4 / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000633:toxicity*; D013997:Time Factors
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D013111:Spider Venoms