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Two Approaches for the Reversal of Phenobarbital-Induced Behavioral Birth Defects

  • Conference paper
Neuronal Grafting and Alzheimer’s Disease

Part of the book series: Research and Perspectives in Alzheimer’s Disease ((ALZHEIMER))

Summary

The present chapter presents a model for the reversal of behavioral birth defects. Since the neuroteratogen employed, phenobarbital, alters numerous processes and behaviors, the study focused on alterations in the hippocampus and its related behaviors. Mice were exposed to phenobarbital prenatally, although some of the experiments also included neonatally exposed groups. At adulthood they showed deficits in spontaneous alternation, Morris maze and eight-arm maze tests. Studies on hippocampal morphology revealed areal and cell losses and deficient dendritic architecture in the surviving neurons, including reductions from control in the number of dendritic branches, area, and spine density, but wider fission angle than control. Neurochemical studies on the hippocampus revealed the following alterations:

  1. 1.

    decrease in norepinephrine (NE) level and the number of NE cell bodies,

  2. 2.

    no change in the serotonergic system,

  3. 3.

    an increase in muscarinic receptors B max in the hippocampus,

  4. 4.

    transient decrease in gamma-aminobutyric acid (GABA) uptake, and an increase in the B max of GABA and benzodiazepine receptors.

The changes in GABA did not correspond with the sensitive periods for the behavioral deficits. Transplantation of cholinergic neurons into the hippocampus of the treated mice reversed most of the deficits in eight-arm maze behavior, while transplantation of noradrenergic cells did not have an effect. Consistently, destruction of the inhibiting dopaminergic innervations in the septum increased hippocampal choline acetyltransferase (ChAT) activity and enabled the treated mice to reach normal performance in the maze after training.

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Authors
  1. J. Yanai
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  2. F. Fares
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  3. M. Gavish
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  4. Z. Greenfeld
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  5. C. G. Pick
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  6. Y. Rogel-Fuchs
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  7. D. Trombkal
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Editor information

Editors and Affiliations

  1. Neurosciences, School of Madicine, M. 024 University of California, 92093, La Jolla, CA, USA

    F. H. Gage

  2. Laboratoire de Neurobiologie, Institut de Biologie, Boulevard Henri IV, F-34060, Montpellier, France

    A. Privat

  3. pour la Recherche Therapeutique, Fondation IPSEN, 30, rue Cambronne, F-75737, Paris Cedex, France

    Yves Christen

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© 1989 Springer-Verlag Berlin Heidelberg

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Yanai, J. et al. (1989). Two Approaches for the Reversal of Phenobarbital-Induced Behavioral Birth Defects. In: Gage, F.H., Privat, A., Christen, Y. (eds) Neuronal Grafting and Alzheimer’s Disease. Research and Perspectives in Alzheimer’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-48369-1_15

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  • DOI: https://doi.org/10.1007/978-3-642-48369-1_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-48371-4

  • Online ISBN: 978-3-642-48369-1

  • eBook Packages: Springer Book Archive

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