Kalpachidou Theodora, Raftogianni Androniki, Melissa Pelagia, Kollia Anna-Maria, Stylianopoulou Fotini, Stamatakis Antonios
Biology-Biochemistry Laboratory, School of Health Sciences, University of Athens, Athens 11527, Greece.
Cereb Cortex. 2016 Sep;26(9):3866-3877. doi: 10.1093/cercor/bhv192. Epub 2015 Aug 26.
The noradrenergic system plays an important role in prefrontal cortex (PFC) function. Since early life experiences play a crucial role in programming brain function, we investigated the effects of a neonatal experience involving reward through maternal contact on the noradrenergic system of the rat PFC. Rat pups were exposed during Postnatal days (PNDs) 10-13, to a T-maze in which contact with the mother was used as a reward (RER). RER males had higher norepinephrine levels in the PFC both on PND 13 and in adulthood. The RER experience resulted in adulthood in increased levels of the active demethylase GADD45b, hypomethylation of the β1 adrenergic receptor (ADRB1) gene promoter, and consequent enhanced expression of its mRNA in the PFC. In addition, protein and binding levels of the ADRB1, as well as those of its downstream effector phosphorylated cAMP response element-binding protein were elevated in RER males. The higher activity of the PFC noradrenergic system of the RER males was reflected in their superior performance in the olfactory discrimination and the contextual fear extinction, 2 PFC noradrenergic system-dependent behavioral tasks.
去甲肾上腺素能系统在额叶前皮质（PFC）功能中发挥着重要作用。由于早期生活经历在大脑功能编程中起着关键作用，我们研究了一种通过母体接触给予奖励的新生期经历对大鼠PFC去甲肾上腺素能系统的影响。在出生后第10 - 13天（PNDs），将幼鼠置于一个T型迷宫中，其中与母亲的接触被用作奖励（RER）。RER组的雄性大鼠在出生后第13天以及成年期时，PFC中的去甲肾上腺素水平均较高。RER经历导致成年期时活性去甲基化酶GADD45b水平升高、β1肾上腺素能受体（ADRB1）基因启动子的低甲基化，进而使其在PFC中的mRNA表达增强。此外，RER组雄性大鼠中ADRB1的蛋白质和结合水平，以及其下游效应物磷酸化的环磷酸腺苷反应元件结合蛋白的水平均有所升高。RER组雄性大鼠PFC去甲肾上腺素能系统的较高活性体现在它们在嗅觉辨别和情境性恐惧消退这两项依赖于PFC去甲肾上腺素能系统的行为任务中的卓越表现上。
