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Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
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Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)

Published on: March 25, 2016

Maternal administration of thalidomide or valproic acid causes abnormal serotonergic neurons in the offspring:

Kaoru Miyazaki1, Naoko Narita, Masaaki Narita

  • 1Neurobiology Laboratory, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-City, Ibaraki 305-8575, Japan.

International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience
|March 8, 2005
PubMed

Insights

Embryonic exposure to thalidomide or valproic acid disrupts early brain development in rats, modeling autism. This study reveals altered serotonin neuron development, suggesting a link to autism

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Autism Research

Background:

  • Autism Spectrum Disorder (ASD) is a neurodevelopmental condition often associated with serotonergic system abnormalities.
  • Embryonic exposure to thalidomide (THAL) and valproic acid (VPA) in rats serves as a relevant model for studying human autism.
  • Previous studies indicate these models exhibit serotonergic system dysfunctions.

Purpose of the Study:

  • To investigate the impact of embryonic THAL/VPA exposure on early serotonergic neuronal development.
  • To determine if THAL/VPA exposure perturbs the differentiation and migration of serotonergic neurons.
  • To explore the role of Sonic hedgehog signaling in mitigating VPA-induced developmental deficits.

Main Methods:

  • Pregnant rats were exposed to THAL or VPA on embryonic day 9.
  • Serotonergic neuron distribution in the dorsal raphe nucleus was analyzed on postnatal day 50.
  • In vitro studies utilized embryonic stem (ES) cell-derived neuronal progenitors to assess VPA effects on serotonergic neuron maturation.
  • Sonic hedgehog was added exogenously in in vitro experiments.

Main Results:

  • Embryonic THAL/VPA exposure caused a significant shift in serotonergic neuron distribution in the dorsal raphe nucleus.
  • This observed alteration suggests abnormal differentiation and migration of serotonergic neurons.
  • In vitro, VPA exposure retarded the maturation of serotonergic neurons derived from ES cells.
  • Addition of Sonic hedgehog partially rescued the VPA-induced retardation of neuronal maturation.

Conclusions:

  • Disruption of early serotonergic neuronal development by embryonic THAL/VPA exposure may contribute to the etiology of autism.
  • The findings highlight the critical role of early neurodevelopmental processes in autism pathogenesis.
  • Modulation of developmental pathways, such as Sonic hedgehog signaling, could be a potential therapeutic target.

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