Madden Amanda M K, Zup Susan L
Graduate Program in Developmental and Brain Sciences, University of Massachusetts Boston, Boston, MA 02125, USA; Psychology Department, University of Massachusetts Boston, Boston, MA 02125, USA.
Graduate Program in Developmental and Brain Sciences, University of Massachusetts Boston, Boston, MA 02125, USA; Psychology Department, University of Massachusetts Boston, Boston, MA 02125, USA.
Physiol Behav. 2014 Apr 10;128:260-9. doi: 10.1016/j.physbeh.2014.01.036. Epub 2014 Feb 11.
There is a striking sex difference in the diagnosis of Autism Spectrum Disorder (ASD), such that males are diagnosed more often than females, usually in early childhood. Given that recent research has implicated elevated blood serotonin (hyperserotonemia) in perinatal development as a potential factor in the pathogenesis of ASD, we sought to evaluate the effects of developmental hyperserotonemia on social behavior and relevant brain morphology in juvenile males and females. Administration of 5-methoxytryptamine (5-MT) both pre- and postnatally was found to disrupt normal social play behavior in juveniles. In addition, alterations in the number of oxytocinergic cells in the lateral and medial paraventricular nucleus (PVN) were evident on postnatal day 18 (PND18) in 5-MT treated females, but not treated males. 5-MT treatment also changed the relative expression of 5-HT(1A) and 5-HT(2A) receptors in the PVN, in males at PND10 and in females at PND18. These data suggest that serotonin plays an organizing role in the development of the PVN in a sexually dimorphic fashion, and that elevated serotonin levels during perinatal development may disrupt normal organization, leading to neurochemical and behavioral changes. Importantly, these data also suggest that the inclusion of both juvenile males and females in studies will be necessary to fully understand the role of serotonin in development, especially in relation to ASD.
自闭症谱系障碍（ASD）的诊断存在显著的性别差异，男性的诊断率高于女性，通常在幼儿期。鉴于最近的研究表明围产期发育过程中血清素升高（高血清素血症）是ASD发病机制中的一个潜在因素，我们试图评估发育性高血清素血症对幼年雄性和雌性动物社交行为及相关脑形态的影响。结果发现，在出生前和出生后给予5-甲氧基色胺（5-MT）会扰乱幼崽的正常社交玩耍行为。此外，在出生后第18天（PND18），5-MT处理的雌性动物侧脑室旁核（PVN）和内侧脑室旁核中催产素能细胞数量发生改变，而雄性动物未出现这种情况。5-MT处理还改变了PVN中5-HT(1A)和5-HT(2A)受体的相对表达，在PND10的雄性动物和PND18的雌性动物中均有此现象。这些数据表明，血清素在PVN的发育中以性别二态性方式发挥组织作用，围产期发育过程中血清素水平升高可能会扰乱正常组织，导致神经化学和行为变化。重要的是，这些数据还表明，在研究中纳入幼年雄性和雌性动物对于全面理解血清素在发育中的作用，尤其是与ASD相关的作用是必要的。
