Chronische Hyponatriämie und ihre Auswirkungen auf das Gehirn bei gesunden Ratten und Ratten mit Östrogenmangel

Mild chronic hyponatremia (HypoNa) is the most common clinical electrolyte disturbance. Once thought to be asymptomatic due to brain adaptation, recent evidence suggests that chronic HypoNa is associated with attention deficit, risk of falls and cognitive impairment. Such neurological deficits are associated with reduced quality of life and may be a significant cause of mortality. Here we investigated the effect of chronic HypoNa on the expression level of some genes in the brain of healthy or estrogen deficient rats.

7-month-old female rats were either ovariectomised (OVX) or SHAM ovariectomised (SHAM). In both OVX and SHAM groups, HypoNa was induced by desmopressin in the s.c. pump. Saline was used in the vehicle groups. After 6 weeks, the first cohort was sacrificed and the other cohort had the pumps replaced for a further 6 weeks (12-week group). RNA was isolated from rat brains and the expression of the following genes was analyzed by quantitative PCR; PLP, MOG, Slac2a1, Slac2a3, CASP3 and BCL2.

Examination of the myelin marker genes MOG and PLP showed that the expression of the MOG gene was significantly increased in SHAM-HypoNa for 6 or 12 weeks (p*, P**) compared to SHAM. There were no differences between the OVX and OVX-HypoNa groups. There were also no changes in the expression of glucose transporter genes (Slac2a1-GLUT1, Slac2a3-GLUT3) or in caspase 3 (CASP3). On the other hand, BCL2 was significantly reduced in the OVX HypoNa-12 weeks group (p*) compared to the OVX group.

Here we show that in the presence of estrogen (SHAM) and under HypoNa conditions, the expression of the myelin gene MOG increased. MOG expression was not significantly different between the OVX groups, confirming the influence (direct or indirect) of estrogen on the expression of this gene in the HypoNa rats. Whether the observed downregulation of BCL2 in OVX-HypoNa promotes cell survival and thus the known adaptive mechanism that counteracts the negative effects of HypoNa on the brain, will be further investigated.