Autism Research Today is a free monthly online journal that collates and summarizes the latest research about Autism, including details on symptoms, diagnosis, treatment, causes, effects.

Altered neocortical cell density and layer thickness in serotonin transporter knockout mice: a quantitation study.

Altamura C, Dell'Acqua ML, Moessner R, Murphy DL, Lesch KP, Persico AM

Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Via Longoni 83, I-00155 Rome, Italy.

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 ko 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.

Published 11 May 2007 in Cereb Cortex, 17(6): 1394-401.
Full-text of this article is available online (may require subscription).

© 2004-2008 Autism Research Today. All Rights Reserved.