title: Hippocampal mitochondrial dysfunction with decreased mtNOS activity in prehepatic portal hypertensive rats.
abstract: Portal hypertension is a major complication of human cirrhosis that frequently leads to central nervous system dysfunction. In our study, rats with prehepatic portal hypertension developed hippocampal mitochondrial dysfunction as indicated by decreased respiratory rates, respiratory control and mitochondrial nitric oxide synthase (mtNOS) activity in mitochondria isolated from the whole hippocampus. Succinate-dependent respiratory rates decreased by 29% in controlled state 4 and by 42% in active state 3, and respiratory control diminished by 20%. Portal hypertensive rats showed a decreased mtNOS activity of 46%. Hippocampal mitochondrial dysfunction was associated with ultrastructural damage in the mitochondria of hippocampal astrocytes and endothelial cells. Swollen mitochondria, loss of cristae and rupture of outer and inner membrane was observed in astrocytes and endothelial cells of the blood-brain barrier in parallel with the ammonia gradient. It is concluded that the moderate increase in plasma ammonia that followed portal hypertension was the potential primary cause of the observed alterations.
authors: Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina. slarnaiz@ffyb.uba.ar
authors: Silvia
authors: S
authors: Lores-Arnaiz
authors: Juan Carlos
authors: JC
authors: Perazzo
authors: Juan Pablo
authors: JP
authors: Prestifilippo
authors: Néstor
authors: N
authors: Lago
authors: Gabriela
authors: G
authors: D'Amico
authors: Analía
authors: A
authors: Czerniczyniec
authors: Juanita
authors: J
authors: Bustamante
authors: Alberto
authors: A
authors: Boveris
authors: Abraham
authors: A
authors: Lemberg
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D006975:Hypertension, Portal / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D010101:Oxygen Consumption / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009419:Nerve Tissue Proteins; D000644:Quaternary Ammonium Compounds; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat