Growth retardation and altered autonomic control in mice lacking brain serotonin
Growth retardation and altered autonomic control in mice lacking brain serotonin
复制标题
DOI：
10.1073/pnas.0810793106
复制
发表时间：
2009-06-23
影响因子：
11.1
通讯作者：
Bader, Michael
中科院分区：
文献类型：
--
作者：
Alenina, Natalia;Kikic, Dana;Bader, Michael
哺乳动物中的5-羟色胺合成由两种不同的色氨酸羟化酶（TPH）TPH 1和TPH 2启动。通过基因切除TPH 2，我们创造了中枢神经系统缺乏血清素的小鼠（Tph 2（-/-））。令人惊讶的是，这些老鼠可以出生并存活到成年。然而，大脑中5-羟色胺信号的消耗导致生长迟缓和出生后前4周内50%的死亡率。遥测监测显示Tph 2（-/-）小鼠白天睡眠时间延长，呼吸抑制，体温控制改变，夜间血压（BP）和心率（HR）降低。此外，Tph 2（-/-）雌性尽管具有生育能力并产奶，但表现出受损的母性护理，导致其幼崽存活率低。这些数据证实，大多数中枢5-羟色胺是由TPH 2产生的。TPH 2衍生的5-羟色胺参与行为和自主神经通路的调节，但对成年生活不是必需的。
Serotonin synthesis in mammals is initiated by 2 distinct tryptophan hydroxylases (TPH), TPH1 and TPH2. By genetically ablating TPH2, we created mice (Tph2(-/-)) that lack serotonin in the central nervous system. Surprisingly, these mice can be born and survive until adulthood. However, depletion of serotonin signaling in the brain leads to growth retardation and 50% lethality in the first 4 weeks of postnatal life. Telemetric monitoring revealed more extended daytime sleep, suppressed respiration, altered body temperature control, and decreased blood pressure (BP) and heart rate (HR) during nighttime in Tph2(-/-) mice. Moreover, Tph2(-/-) females, despite being fertile and producing milk, exhibit impaired maternal care leading to poor survival of their pups. These data confirm that the majority of central serotonin is generated by TPH2. TPH2-derived serotonin is involved in the regulation of behavior and autonomic pathways but is not essential for adult life.