The effect of pre-eclampsia-like syndrome induced by L-NAME on learning and memory and hippocampal glucocorticoid receptor expression: A rat model

ABSTRACT

Objective: We aimed to study the impacts of pre-eclampsia on the cognitive and learning capabilities of adolescent rat offspring and to explore the possible underlying mechanisms at the molecular level. Methods: Pregnant rats were subcutaneously injected with saline solution (control) (n = 16) or NG-nitro-L-arginine methyl ester (L-NAME) (n = 16) from the 13th day of gestation until parturition. The brain tissues from fetal rats delivered by cesarean section were examined in both groups with hematoxylin and eosin (H&E) staining. Rats born vaginally in both groups were subjected to the Morris water maze test when 8-week-old and their hippocampi were analyzed for glucocorticoid receptor (GR) expression. Results: A pre-eclampsia-like model was successfully built in pregnant rats by infusion of the NO synthase inhibitor L-NAME, including phenotypes as maternal hypertension and proteinuria, high stillbirth rate, and fetal growth retardation. Neuroepithelial cell proliferation was found in the hippocampus of fetal rats in the L-NAME group. Grown to 8-week-old, the L-NAME group showed significantly longer escape latency than the control group in the beginning as well as in the end of navigation trials. At the same time, the swimming distance achieved by the L-NAME group was significantly longer than that of the control group. Such differences in cognitive and learning capabilities between the two groups were not gender dependent. Besides, the 8-week-old rats in the L-NAME group had increased GR expression in the hippocampus than the control group. Conclusion: Pre-eclampsia would impair cognitive and learning capabilities in adolescent offspring, and the upregulated expression of hippocampal GR may be involved in the underlying mechanisms.

KEYWORDS:

• Glucocorticoid receptors
• hippocampus
• learning and memory
• Morris water maze
• pre-eclampsia

Funding

This work was supported in part by the Fund of Science and Technology Commission of Shanghai (064909006), National Key Basic Research Plan of China (973 Plan; Grant No.: 2010CB529500), National Science Fund of China (Grant No.: 30872777), the Key Project of Clinical Disciplines of Chinese Ministry of Health (Grant No.: 2007-353), and the Key Projects in the National Science and Technology Pillar Program of the Eleventh Five-year Plan Period (Grant No. 2006BAI05A05).

Conflict of interests

All authors declare that they have no conflict of interests.

Additional information

Funding

This work was supported in part by the Fund of Science and Technology Commission of Shanghai (064909006), National Key Basic Research Plan of China (973 Plan; Grant No.: 2010CB529500), National Science Fund of China (Grant No.: 30872777), the Key Project of Clinical Disciplines of Chinese Ministry of Health (Grant No.: 2007-353), and the Key Projects in the National Science and Technology Pillar Program of the Eleventh Five-year Plan Period (Grant No. 2006BAI05A05).