Trichostatin A Ameliorates Spatial Memory Deficits and Suppresses Hippocampal Pro- Inflammatory Cytokines in A Rat Model of Prenatal Stress

Introduction: Maternal stress during pregnancy leads to neuroinflammation of the fetus and cognitive disorders in children. On the other side, Trichostatin A (TSA) as a histone deacetylase inhibitor has anti-inflammatory and neuroprotective effects. The aim of the present study was an evaluation of TSA effect on amelioration of spatial memory deficit and modification of pro-inflammatory cytokines in rat’s hippocampus of prenatal footshock stress model. Methods: In the present study, ۲۴ pregnant Wistar rats were divided into ۴ groups including control, PFS+Saline, PFS+TSA۵, and PFS+TSA۱۰. In order to induce prenatal footshock stress (PFS), the pregnant rats were subjected to electrical shock at ۱ mA, ۵۰ Hz for ۲ seconds with ۵ repetitions at ۳-minute intervals from ۱۲ to ۱۸ days of pregnancy. Two hours before applying the shock intraperitoneal administration of TSA was performed daily. When the offsprings were one-month old, their spatial memory was assessed by the Morris water maze. Finally, the levels of pro-inflammatory cytokines (TNF-α, IL-۱β, and IL-۶) were measured by ELISA method. Results: a reduction in spatial memory and an increase in the level of TNF-α, IL-۱β, and IL-۶ were observed in PFS+Saline group compared to the control. Besides, spatial learning showed a significant increase in TSA-treated groups compared to PFS+Saline. Conclusion: TSA with anti-inflammatory effects led to the reduction of hippocampal inflammatory cytokines and amelioration of spatial memory in offsprings who were exposed to stress in the prenatal period.

Keywords:

Prenatal Stress , Inflammatory Cytokine , Hippocampus , Rat