title: Increased aquaporin-1 and Na+ -K+ -2Cl- cotransporter 1 expression in choroid plexus leads to blood-cerebrospinal fluid barrier disruption and necrosis of hippocampal CA1 cells in acute rat models of hyponatremia.
abstract: Hyponatremia is a metabolic disorder characterized by increased cerebrospinal fluid (CSF) volume and pressure, although the site of brain insult is unclear. Specifically, the hippocampus, which is in direct contact with expanding CSF ventricles, may be involved. The present study was undertaken to investigate the possible roles of choroid plexus aquaporin-1 (AQP1) and of cation chloride transporters (Na(+) -K(+) -2Cl(-) cotransporter 1 [NKCC1] and K(+) -Cl(-) cotransporter 4 [KCC4]) in the underlying hippocampal pathophysiology of hyponatremia in acute (6 and 12 hr duration) experimental models. It was found that the expressions of AQP1 and NKCC1 proteins in choroid plexus were significantly increased, whereas the expression of KCC4 protein was unchanged vs. control values after 6 and 12 hr of hyponatremia. Choroid plexuses with increased AQP1 and NKCC1 after 6 hr of hyponatremia showed caspase 3-dependent apoptosis and disruption of the blood-CSF barrier. Furthermore, necrotic changes in CA1 neuronal cells were observed after 6 and 12 hr of hyponatremia. Overall, these data suggest that increases in AQP1 and NKCC1 expression under hyposmotic stress may be one of the molecular mechanisms underlying the pathophysiology of acute hyponatremia, such as the necrotic cell death of hippocampal CA1 region by increasing water transport across the blood-CSF barrier. Furthermore, we suggest that opening of the blood-CSF barrier after acute hyponatremia may be triggered the secondary adverse conditions that are capable of enhancing selective necrosis in hippocampal CA1 cells.
authors.affiliation: Department of Anatomy, College of Medicine, Dongguk University, Gyeongju, Republic of Korea.
authors.forename: Jaehyun
authors.initials: J
authors.lastname: Kim
authors.forename: Yongwook
authors.initials: Y
authors.lastname: Jung
mesh_terms: D000208:Acute Disease; D000818:Animals; D051398:Aquaporin 1 / Q000096:biosynthesis / Q000235:genetics*; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000503:physiopathology*; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism*; D004195:Disease Models, Animal; D007010:Hyponatremia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis / Q000235:genetics*; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics*; D000096922:K Cl- Cotransporters
chemical_list: D051398:Aquaporin 1; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; C496022:Aqp1 protein, rat; C578879:Slc12a2 protein, rat; C492283:Slc12a7 protein, rat; D000096922:K Cl- Cotransporters