Monoamine oxidases regulate telencephalic neural progenitors in late embryonic and early postnatal development

Aiwu Cheng, Anna L. Scott, Bruce Ladenheim, Kevin Chen, Xin Ouyang, Justin D. Lathia, Mohamed Mughal, Jean Lud Cadet, Mark P. Mattson, Jean C. Shih

Research output: Contribution to journalArticle

Abstract

Monoamine neurotransmitters play major roles in regulating a range of brain functions in adults and increasing evidence suggests roles for monoamines in brain development. Here we show that mice lacking the monoamine metabolic enzymes MAO A and MAO B (MAO AB-deficient mice) exhibit diminished proliferation of neural stem cells (NSC) in the developing telencephalon beginning in late gestation [embryonic day (E) 17.5], a deficit that persists in neonatal and adult mice. These mice showed significantly increased monoamine levels and anxiety-like behaviors as adults. Assessments of markers of intermediate progenitor cells (IPC) and mitosis showed that NSC in the subventricular zone (SVZ), but not in the ventricular zone, are reduced in MAO AB-deficient mice. A developmental time course of monoamines in frontal cortical tissues revealed increased serotonin levels as early as E14.5, and a further large increase was found between E17.5 and postnatal day 2. Administration of an inhibitor of serotonin synthesis (parachlorophenylalanine) between E14.5 and E19.5 restored the IPC numbers and SVZ thickness, suggesting the role of serotonin in the suppression of IPC proliferation. Studies of neurosphere cultures prepared from the telencephalon at different embryonic and postnatal ages showed that serotonin stimulates proliferation in wild-type, but not in MAO AB-deficient, NSC. Together, these results suggest that a MAO-dependent long-lasting alteration in the proliferation capacity of NSC occurs late in embryonic development and is mediated by serotonin. Our findings reveal novel roles for MAOs and serotonin in the regulation of IPC proliferation in the developing brain.

Original languageEnglish (US)
Pages (from-to)10752-10762
Number of pages11
JournalJournal of Neuroscience
Volume30
Issue number32
DOIs
StatePublished - Aug 11 2010

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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    Cheng, A., Scott, A. L., Ladenheim, B., Chen, K., Ouyang, X., Lathia, J. D., Mughal, M., Cadet, J. L., Mattson, M. P., & Shih, J. C. (2010). Monoamine oxidases regulate telencephalic neural progenitors in late embryonic and early postnatal development. Journal of Neuroscience, 30(32), 10752-10762. https://doi.org/10.1523/JNEUROSCI.2037-10.2010