Reversal of neurobehavioral teratogenicity in animal models and human: Three decades of progress

Joseph Yanai1, Myles J Vigoda2, Asher Ornoy3

  • 1The Ross Laboratory for Studies in Neural Birth Defects, Department of Medical Neurobiology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel; Department of Pharmacology and Cancer Biology, Duke University Medical Center Durham, NC, USA.

Insights

Behavioral teratology research has advanced from description to mechanism-driven science, achieving complete reversal of deficits in animal models. However, clinical translation for human neurodevelopmental disorders remains limited, showing only partial improvements.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Toxicology

Background:

  • Early behavioral teratology studies were descriptive.
  • Mechanism-driven research enabled reversal of teratogen-induced deficits starting in the 1980s.
  • Significant progress has been made in animal models, demonstrating long-term reversal of developmental deficits.

Purpose of the Study:

  • To review the progress in behavioral teratology, focusing on the transition from descriptive studies to mechanism-driven research.
  • To evaluate the success of reversing teratogen-induced deficits in animal models.
  • To assess the current clinical translation of these findings for human neurodevelopmental disorders.

Main Methods:

  • Review of published studies on behavioral teratology and reversal of teratogen-induced deficits.
  • Summarization of findings in Tables 1 and 2 (not provided in the abstract).
  • Analysis of clinical findings and translational challenges.

Main Results:

  • Complete and long-term reversal of deficits achieved in numerous animal models.
  • Studies on recovery show persistence with consistent treatment.
  • Clinical translation is incipient, with emerging partial alleviation in humans (e.g., FASD children with choline).

Conclusions:

  • While animal model research on mechanisms and reversal is crucial, the primary focus should shift to translating findings into clinical practice.
  • Current clinical interventions for neurodevelopmental disorders yield partial and potentially non-lasting results.
  • Further research is needed to bridge the gap between animal model successes and effective human clinical treatments.

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