Epigenetic regulation of early life stress on adult fear conditioning

• Main Authors: Ling-YiCheng, 鄭令宜
• Other Authors: Lung Yu
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/90121974982898922466

碩士 === 國立成功大學 === 行為醫學研究所 === 98 === Early life stress has been highlighted in numerous studies as an important influence on later behaviors but seldom has epigenetics been implicated as the mechanism via which this process takes place. In this study we attempted to investigate alterations in DNA methylation and/or histone deacetylation associated with an early life isolation stress and their impact upon fear memory in adulthood. Daily isolation from the dam and siblings from day 2 to 9 post partum (1 hr/day) was utilized as the method of early life stress and a fear potentiated startle (FPS) paradigm was used to examine fear conditioning in adult rats. Our findings revealed that rats exposed to neonatal isolation stress had a diminished conditioning aptitude in the fear potentiated startle test compared to their siblings that had not experienced isolation stress. We further explored whether this effect could be reversed by valproic acid, a histone deacytylase inhibitor. Pups were injected intraperitoneally (i.p.) with valproic acid in high (300mg/kg), medial (100-200-300mg/kg), or low (100-200mg/kg) dose in 0.9% saline solution prior to their isolation. Control groups were injected i.p. with an equivalent volume of saline solution. Results indicated that the VPA-treated groups had a higher fear conditioning aptitude, in comparison to that of the saline-treated group, indicating a reversal of stress-decreased fear potentiation. We conclude that lowered startle potentiation caused by early life stress may be due to stress-induced histone deacetylation.