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新生儿氟西汀暴露影响大鼠皮质基板神经元的动作电位特性和树突发育。

Neonatal fluoxetine exposure affects the action potential properties and dendritic development in cortical subplate neurons of rats.

机构信息

Graduate Institute of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan.

出版信息

Toxicol Lett. 2011 Dec 15;207(3):314-21. doi: 10.1016/j.toxlet.2011.09.028. Epub 2011 Oct 1.

Abstract

Selective serotonin reuptake inhibitor (SSRI)-type antidepressants might be given to depressive pregnant women and the developing fetuses are thus exposed to these drugs. Since serotonin plays important roles in the maturation of the nervous system, early SSRI exposure might influence the fetal brain development. To test this hypothesis, we treated the neonatal rat pups with fluoxetine (Flx) from the day of birth to postnatal day (P) 4, comparable to the third trimester of human gestation, and observed the physiological and morphological features of subplate neurons (SPns), a group of cells important for early cortical development and vulnerable to neonatal neural insults. Using whole-cell patch-clamp recording technique, we examined the passive membrane properties and characteristics of action potential (AP). In SPns of Flx-treated rats, the rheobase for generating an AP was increased and the width of APs was reduced, especially in the falling phase. In the morphological aspect, the dendritic remodeling of SPns including dendritic branching, elongation and pruning were affected by early Flx treatment. Together, our results demonstrate that the teratogenic effect of early SSRI exposure on the structure and function of developing SPns and these changes may lead to undesired brain activity and distorted behaviors later in life.

摘要

选择性 5-羟色胺再摄取抑制剂(SSRIs)类抗抑郁药可能会被用于治疗患有抑郁症的孕妇,因此发育中的胎儿会接触到这些药物。由于 5-羟色胺在神经系统成熟过程中发挥着重要作用,早期 SSRIs 暴露可能会影响胎儿大脑发育。为了验证这一假设,我们在新生大鼠出生后的第 1 天至第 4 天(相当于人类妊娠的第三个 trimester)给予氟西汀(Flx)治疗,并观察了基板神经元(SPns)的生理和形态特征,基板神经元是一组对于早期皮层发育很重要且易受新生儿神经损伤影响的细胞。我们使用全细胞膜片钳记录技术,研究了被动膜特性和动作电位(AP)的特征。在 Flx 处理的大鼠的 SPns 中,产生 AP 的激发电流阈值增加,AP 的宽度减小,尤其是在下降阶段。在形态方面,早期 Flx 处理会影响 SPns 的树突重塑,包括树突分支、伸长和修剪。总之,我们的研究结果表明,早期 SSRIs 暴露对发育中的 SPns 的结构和功能具有致畸作用,这些变化可能会导致日后生活中出现不期望的大脑活动和行为扭曲。

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