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

Abstract

OBJECTIVE: 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. STUDY DESIGN: Pregnant rats at 16, 18 and 20 days of gestation (60 total: 8 groups, n¼5) 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. RESULTS: 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 1.0AE0.01, 1.21AE.0.02, 0.78AE0.16; miR-132 1.0AE0.01, 1.19AE0.03, 0.86AE0.1, respectively). At e16 maternal LPS decreased fetal brain AChE (0.62AE0.1), and miR-132 mRNA expression (0.72AE0.11) compared to control (p< 0.05). Maternal Mg alone increased both fetal brain AChE and miR-132 mRNA expression at e16 (AChE1.7AE0.15; miR-132 1.7AE0.16) 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 (1.15AE0.04;1.25AE0.1 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. CONCLUSION: 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.