Growth retardation and altered autonomic control in mice lacking brain serotonin

被引：276

作者：

Alenina, Natalia ^{[1
]}

Kikic, Dana ^{[1
]}

Todiras, Mihail ^{[1
]}

Mosienko, Valentina ^{[1
]}

Qadri, Fatimunnisa ^{[1
]}

Plehm, Ralph ^{[1
]}

Boye, Philipp ^{[1
]}

Vilianovitch, Larissa ^{[1
]}

Sohr, Reinhard ^{[2
]}

Tenner, Katja ^{[1
]}

Hoertnagl, Heide ^{[2
]}

Bader, Michael ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

[2] Charite, Inst Pharmacol, D-10117 Berlin, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 25期

关键词：

growth retardation; maternal care; respiration; serotonin; sleep; PERFORMANCE LIQUID-CHROMATOGRAPHY; TRYPTOPHAN-HYDROXYLASE ISOFORM; PLATELET-DERIVED SEROTONIN; NEURONS; GENE; RAT; DEFICIENCY; BEHAVIOR; 5-HT; ACID;

D O I：

10.1073/pnas.0810793106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：10332 / 10337

页数：6

共 41 条

[1] Stress upregulates TPH1 but not TPH2 mRNA in the rat dorsal raphe nucleus:: Identification of two TPH2 mRNA splice variants [J].