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Formation of the neocortex in mice developing in conditions of prenatal serotonin deficiency

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Abstract

We report here detailed studies of structural changes occurring in the mouse neocortex formed and stratified in conditions of prenatal experimental blockade of serotonin synthesis. Studies were performed using F1(C57BL/CBA) hybrid mice. Endogenous serotonin levels were decreased by exposure of the mice to parachlorophenylalanine, which inhibits the key serotonin synthesis enzyme tryptophan hydroxylase. Offspring brains were studied at 1, 5 and 10 days (n = 10–15 for each time point) of postnatal development. Controls consisted of intact animals at the same periods of development. These experiments showed that prenatal blockade of serotonin synthesis leads to impaired formation of all neocortical layers, impaired growth, development, and differentiation of neurons, and alterations in neuron shape and size. As postnatal development proceeded, significant numbers of neurons died in the brain structures of these animals.

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References

  1. G. A. Buznikov, Neurotransmitters in Embryogenesis [in Russian], Nauka, Moscow (1967).

    Google Scholar 

  2. G. Z. Buznikov, Yu. B. Shmukler, and D. M. Lauder, “Changes in the physiological role of neurotransmitters during individual development,” Ros. Fiziol. Zh., 83, No. 10, 1–15 (1997).

    CAS  Google Scholar 

  3. E. V. Naumenko, Central Regulation of the Hypophyseal-Adrenal Complex [in Russian], Nauka, Leningrad (1971).

    Google Scholar 

  4. L. I. Khozhai and V. A. Otellin, “Morphogenesis of layer I of the mouse cortex during the prenatal period of development,” Ontogenez, 30, No. 1, 40–46 (1999).

    CAS  PubMed  Google Scholar 

  5. L. I. Khozhai, V. F. Puchkov, and V. A. Otellin, “Effects of serotonin deficit on embryonic development in mammals,” Ontogenez, 26, No. 5, 350–355 (1995).

    CAS  PubMed  Google Scholar 

  6. J. E. Aldridge, F. J. Seidler, A. Meyer, et al., “Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods,” Environ. Health Perspect., 111, No. 14, 1736–1743 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. G. A. Buznikov, Neurotransmitters in Embryogenesis, Harwood Academic Press, Chur. (1990).

    Google Scholar 

  8. P. Gaspar, “Genetic models to understand how serotonin acts during development,” J. Soc. Biol., 198, No. 1, 18–21 (2004).

    CAS  PubMed  Google Scholar 

  9. R. P. Hellendall, U. Shambra, J. Liu, and J. M. Lauder, “Prenatal expression of 5-HT1c and 5-HT receptors in the developing nervous system,” Exptl. Neurol., 120, No. 2, 186–201 (1993).

    Article  CAS  Google Scholar 

  10. N. Ivgy-May, H. Tamir, and M. D. Gershon, “Synaptic properties of serotonergic growth cones in developing rat brain,” J. Neurosci., 4, No. 3, Part 1, 1011–1029 (1994).

    Google Scholar 

  11. S. Janusonis, V. Gluncic, and P. Rakic, “Early serotonergic projections to Cajal—Retzius cells: relevance for cortical development,” J. Neurosci., 24, No. 7, 1652–1659 (2004).

    Article  CAS  PubMed  Google Scholar 

  12. H. H. Keller, “Depletion of cerebral monoamines by p-chlorophenylalanine in the cat,” Experientia, 28, No. 2, 177–178 (1972).

    Article  CAS  PubMed  Google Scholar 

  13. J. M. Lauder, “Neurotransmitters as morphogens,” Prog. Brain Res., 73, 365–387 (1988).

    Article  CAS  PubMed  Google Scholar 

  14. J. M. Lauder, “Ontogeny of the serotonergic system in the rat. Serotonin as a developmental signal,” Ann. N.Y. Acad. Sci., 600, 297–314 (1990).

    CAS  PubMed  Google Scholar 

  15. J. M. Lauder, H. Tamir, and T. W. Sadler, “Serotonin and morphogenesis I. Sites of serotonin uptake and binding protein immunoreactivity in the midgestation mouse embryo,” Dev, 102, No. 4, 709–720 (1988).

    CAS  Google Scholar 

  16. J. M. Lauder, A. C. Towle, and K. Patric, “Decreased serotonin content of embryonic raphe neurons following maternal administration of p-chlorophenylalanine: a quantitative immunocytochemical study,” Dev. Brain Res., 20, No. 1, 107–114 (1985).

    Article  CAS  Google Scholar 

  17. X. Luo, A. M. Persico, and J. M. Lauder, “Serotonergic regulation of somatosensory cortical development: lessons from genetic mouse models,” Dev. Neurosci., 25, No. 2–4, 173–183 (2003).

    Article  CAS  PubMed  Google Scholar 

  18. T. Vitalis and J. G. Parnavelas, “The role of serotonin in early cortical development,” Dev. Neurosci., 25, No. 204, 245–246 (2003).

    Article  CAS  PubMed  Google Scholar 

  19. P. M. Whitaker-Azmitia, A. V. Shemer, J. Caruso, et al., “Role of high affinity serotonin receptors in neuronal growth,” Ann. N.Y. Acad. Sci., 600, 315–330 (1990).

    CAS  PubMed  Google Scholar 

  20. M. S. Yavarone, D. L. Shuey, T. W. Sadler, and J. M. Lauder, “Serotonin uptake in the ectoplacental cone and placenta of the mouse,” Placenta, 14, No. 2, 149–161 (1993).

    CAS  PubMed  Google Scholar 

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Translated from Morfologiya, Vol. 127, No. 3, pp. 17–20, May–June, 2005.

Corresponding Member of the Russian Academy of Medical Sciences

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Khozhai, L.I., Otellin, V.A. Formation of the neocortex in mice developing in conditions of prenatal serotonin deficiency. Neurosci Behav Physiol 36, 513–517 (2006). https://doi.org/10.1007/s11055-006-0048-2

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  • DOI: https://doi.org/10.1007/s11055-006-0048-2

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