Altered neocortical cell density and layer thickness in serotonin transporter knockout mice: A quantitation study
Altered neocortical cell density and layer thickness in serotonin transporter knockout mice: A quantitation study
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DOI：
10.1093/cercor/bhl051
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发表时间：
2007-06-01
期刊：
影响因子：
3.7
通讯作者：
Persico, Antonio M.
中科院分区：
文献类型：
--
作者：
Altamura, C.;Dell'Acqua, M. L.;Persico, Antonio M.
神经递质5-羟色胺(5-羟色胺)在发育过程中起着形态发生的作用，其变化可能在人类自闭症的发病机制中起作用。为了进一步确定5-羟色胺对新皮质发育的贡献，我们评估了5-羟色胺转运体(5-HTT)基因敲除(KO)小鼠大脑皮层不同区域的厚度和神经细胞密度，其特征是细胞外5-羟色胺水平升高。与野生型(Wt)小鼠相比，5-HTT Ko小鼠的IV层厚度减少。然而，对皮质厚度的总体影响取决于小鼠的遗传背景。具有C129-CD1-C57BL/6J混合背景的5-HTT Ko小鼠的许多皮质区域的总皮质厚度降低。取而代之的是，5-HTT ka小鼠回交到C57BL/6J背景显示颗粒上和颗粒下层增加，这完全补偿了IV层厚度的减少，导致皮质厚度保持不变甚至增加。此外，具有C57BL/6J背景(wt：hz：ko=1.00：1.04：1.17)的5-HTT Ko小鼠的神经细胞密度显著增加，而混合C129-CD1-C57BL/6J 5-HTT Ko小鼠的神经细胞密度没有明显增加。这些结果提供了5-HTT基因在与其他基因座的遗传变异上位性相互作用中对新皮质形态影响的证据，并可能模拟功能性5-HTT基因变异对自闭症新皮质发育的影响。
The neurotransmitter serotonin (5-HT) plays morphogenetic roles during development, and their alteration could contribute to autism pathogenesis in humans. To further characterize 5-HT's contributions to neocortical development, we assessed the thickness and neuronal cell density of various cerebral cortical areas in serotonin transporter (5-HTT) knockout (ko) mice, characterized by elevated extracellular 5-HT levels. The thickness of layer IV is decreased in 5-HTT ko mice compared with wild-type (wt) mice. The overall effect on cortical thickness, however, depends on the genetic background of the mice. Overall cortical thickness is decreased in many cortical areas of 5-HTT ko mice with a mixed c129-CD1-C57BL/6J background. Instead, 5-HTT ka mice backcrossed into the C57BL/6J background display increases in supragranular and infragranular layers, which compensate entirely for decreased layer IV thickness, resulting in unchanged or even enhanced cortical thickness. Moreover, significant increases in neuronal cell density are found in 5-HTT ko mice with a C57BL/6J background (wt:hz:ko ratio = 1.00:1.04:1.17) but not in the mixed c129-CD1-C57BL/6J 5-HTT ko animals. These results provide evidence of 5-HTT gene effects on neocortical morphology in epistatic interaction with genetic variants at other loci and may model the effect of functional 5-HTT gene variants on neocortical development in autism.