Beta-hydroxy-butyrate alters the extracellular content of S100B in astrocyte cultures.
Astrocytes have a variety of roles in maintaining neural tissue physiology, including energetic support, uptake and metabolism of glutamate and secretion of neurotrophic factors. Glutamate toxicity has been implicated in neurodegenerative disorders associated with conditions related to energy failure, and to elevation of glutamate extracellular levels in brain. Glucose is the main energetic substrate for brain cells but, in some circumstances, the ketone bodies are used as a supplementary source and have been suggested to be neuroprotective agents against seizure disorders. Here, we investigate some possible biochemical changes in astrocyte cultures induced by beta-hydroxy-butyrate, the predominant blood ketone body. Its effect upon S100B secretion, astrocyte morphology and glutamate uptake was particularly investigated. S100B, a calcium-binding protein expressed and secreted by astrocytes, has neurotrophic activity and a possible role in epileptogenesis. Cell morphology was investigated by phase-contrast microscopy and immunocytochemistry for actin, GFAP and S100B. Our data show that beta-hydroxy-butyrate induces dramatic changes in astrocyte morphology and, independent of this, causes changes in the extracellular content of S100B. We observed an increment in S100B 1 h after beta-hydroxy-butyrate addition and a decrease 24 h later. No changes were observed in glutamate uptake. These astrocytic modifications may be associated with reduced neuronal excitability observed in the ketogenic condition.
Leite
Marina
M
Depto Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-anexo, Porto Alegre 90035-003, Brazil.
Frizzo
Juliana K
JK
Nardin
Patrícia
P
de Almeida
Lúcia Maria Vieira
LM
Tramontina
Francine
F
Gottfried
Carmem
C
Gonçalves
Carlos-Alberto
CA
D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008246:Lysophospholipids / Q000494:pharmacology; D050178:Monoglycerides; D051381:Rats; D017208:Rats, Wistar; D009418:S100 Proteins / Q000378:metabolism*; D013997:Time Factors
D000199:Actins; D005904:Glial Fibrillary Acidic Protein; D008246:Lysophospholipids; D050178:Monoglycerides; D009418:S100 Proteins; C012786:bis(monoacylglyceryl)phosphate; D018698:Glutamic Acid; D020155:3-Hydroxybutyric Acid