Postnatal Growth Defects in Mice with Constitutive Depletion of Central Serotonin

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• 作者：Nicolas Narboux-N锚me ; Gaelle Angenard ; Valentina Mosienko ; Friederike Klempin ; Pothitos M. Pitychoutis ; Evan Deneris ; Michael Bader ; Bruno Giros ; Natalia Alenina ; Patricia Gaspar
• 刊名：ACS Chemical Neuroscience
• 出版年：2013
• 出版时间：January 16, 2013
• 年：2013
• 卷：4
• 期：1
• 页码：171-181
• 全文大小：558K
• 年卷期：v.4,no.1(January 16, 2013)
• ISSN：1948-7193

文摘

Although the trophic actions of serotonin (5-HT) are well established, only few developmental defects have been reported in mouse strains with constitutive hyposerotonergia. We analyzed postnatal growth and cortical development in three different mutant mouse strains with constitutive reductions in central 5-HT levels. We compared two previously published mouse strains with severe (鈭?5%) depletions of 5-HT, the tryptophan hydroxylase (Tph) 2鈥?鈥?/sup> mouse line and VMAT2^sert-cre mice, with a new strain, in which VMAT2 deletion is driven by Pet1 (VMAT2^pet1-cre) in 5-HT raphe neurons leading to partial (鈭?5%) reduction in brain 5-HT levels. We find that normal embryonic growth and postnatal growth retardation are common features of all these mouse strains. Postnatal growth retardation varied from mild to severe according to the extent of the brain 5-HT reduction and gender. Normal growth was reinstated in VMAT2^sert-cre mice by reconstituting central 5-HT stores. Growth abnormalities could not be linked to altered food intake or temperature control. Morphological study of the cerebral cortex over postnatal development showed a delayed maturation of the upper cortical layers in the VMAT2^sert-cre and Tph2鈥?鈥?/sup> mice, but not in the VMAT2^pet1-cre mice. No changes in layer-specific gene expression or morphological alterations of barrel cortex development were found. Overall, these observations sustain the notion that central 5-HT signaling is required for the preweaning growth spurt of mouse pups. Brain development appeared to be immune to severe central 5-HT depletion for its overall growth during prenatal life, whereas reduced brain growth and delayed cortical maturation development occurred during postnatal life. Reduced developmental 5-HT signaling during postnatal development might modulate the function and fine structure of neural circuits in ways that affect adult behavior.

Keywords:

Cerebral cortex; development; somatic growth; knockout mice; vesicular monoamine transporter; tryptophan hydroxylase; cux1