805: Fetal brain cholinergic regulation following maternal inflammation and magnesium neuroprotection

Abstract

To determine pregnancy ontogeny of AChE and its regulator miR-132 expression in maternal serum and fetal brain under basal and inflammatory conditions and to study the effect of Magnesium (Mg), a known neuroprotective agent, on AChE and miR-132 expression in the fetal brain. Pregnant rats at 16, 18 and 20 days of gestation (60 total: 8 groups, n=5) received injections of i.p. lipopolysaccharide (LPS; 500 ug/kg) or saline (SAL) at time 0. Dams were randomized to s.c. saline or Mg (270 mg/kg loading followed by 27 mg/kg q20 min) for 2 hours prior to and 2 hours following LPS /saline injections. Rats were sacrificed 4 hours following LPS/SAL injection. Fetal brains were harvested from the treatment groups (LPS/SAL, LPS/Mg, SAL/Mg, SAL/SAL) for AChE and miR-132 mRNA expression (real-time RT-PCR) and maternal serum analyzed for AChE levels. Maternal serum AChE increased from e16 to e18 and e20 (169+25, 232+51,263+59 mg/ml, p< 0.05, respectively). Fetal brain AChE and miR-132 mRNA expression increased (p< 0.05) from e16 to e18 and then decreased at e20 (p< 0.05) (AChE 1.0±0.01, 1.21±.0.02, 0.78±0.16; miR-132 1.0±0.01, 1.19±0.03, 0.86±0.1, respectively). At e16 maternal LPS decreased fetal brain AChE (0.62±0.1), and miR-132 mRNA expression (0.72±0.11) compared to control (p< 0.05). Maternal Mg alone increased both fetal brain AChE and miR-132 mRNA expression at e16 (AChE1.7±0.15; miR-132 1.7±0.16) compared to both control and LPS fetal brains (p< 0.05). Mg treatment to LPS dams (LPS/Mg) increased fetal brain AChE and miR-132 levels (1.15±0.04;1.25±0.1 respectively, p< 0.05) compared to both LPS/SAL and SAL/SAL groups. The same pattern was demonstrated at e18 and e20. No significant change was demonstrated in maternal serum AChE levels following LPS or Mg compared to control. These findings suggest that fetal brain AChE activity is not regulated by miR-132. Mg treatment increases fetal brain AChE mRNA levels under basal conditions and in response to maternal LPS, suggesting that reduced ACh may increase fetal brain inflammatory responses.View Large Image Figure ViewerDownload Hi-res image Download (PPT)