4.7 Article

Apoptotic natural cell death in developing primate dopamine midbrain neurons occurs during a restricted period in the second trimester of gestation

Journal

EXPERIMENTAL NEUROLOGY
Volume 204, Issue 2, Pages 802-807

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2007.01.009

Keywords

dopamine; substantia nigra; apoptosis; development; Parkinson's disease; striatum; tyrosine hydroxylase; primate; monkey

Categories

Funding

  1. NINDS NIH HHS [NS 044281, P01 NS044281, NS 40570, P01 NS044281-05, R21 NS040570, R21 NS040570-03] Funding Source: Medline

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Natural cell death (NCD) by apoptosis is a normal developmental event in most neuronal populations, and is a determinant of the eventual size of a population. We decided to examine the timing and extent of NCD of the midbrain dopamine system in a primate species, as dopamine deficiency or excess has been implicated in several disorders. Genetic or environmental differences may alter the extent of NCD and predispose individuals to neurological or psychiatric diseases. In developing rats, NCD in the midbrain dopamine system has been observed to start at the end of gestation and peak in the postnatal period. In fetal monkey brains, apoptosis in midbrain DA neurons was identified histologically by chromatin clumping in tyrosine hydroxylase-positive cells, and confirmed by TUNEL and active caspase-3 staining. A distinct peak of NCD occurred at about E80, midway through gestation in this species. We estimate that at least 50% of the population may be lost in this process. In other brains we determined biochemically that the onset of apoptosis coincides with the time of greatest rate of increase of striatal DA concentration. Thus, marked apoptotic NCD occurs in the primate midbrain dopamine system half-way through gestation, and appears to be associated with the rapid developmental increase in striatal dopamine innervation. (c) 2007 Elsevier Inc. All rights reserved.

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