Ovarian Steroids Decrease DNA Fragmentation in the Serotonin Neurons of Non-Injured Rhesus Macaques.
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Ovarian Steroids Decrease DNA Fragmentation in the Serotonin Neurons of Non-Injured Rhesus Macaques.
Mol Psychiatry. 2009 Oct 13;
Authors: Lima FB, Bethea CL
We previously found that ovarian steroids promote neuroprotection in serotonin neurons by decreasing the expression of pro-apoptotic genes and proteins in the dorsal raphe nucleus of rhesus macaques, even in the absence of overt injury. In this study, we questioned whether these actions would lead to a reduction in DNA fragmentation in serotonin neurons. Ovariectomized (OVX) rhesus monkeys were implanted with silastic capsules that were empty (placebo) or containing estradiol (E), progesterone (P) or estradiol and progesterone (E+P) for 1 month. In all animals, eight levels of the dorsal raphe nucleus in a rostral-to-caudal direction were immunostained using the terminal deoxynucleotidyl transferase nick end labeling (TUNEL) method. Two staining patterns were observed, which are referred to as type I, with complete dark staining of the nucleus, and type II, with peripheral staining in the perinuclear area. A montage of the dorsal raphe was created at each level with a Marianas Stereology Microscope and Slidebook 4.2, and the TUNEL-positive cells were counted. In direct comparison with OVX animals, P treatment and E+P treatment significantly reduced the total number of TUNEL-positive cells (Mann-Whitney test, both treatments P=0.04) and E+P treatment reduced the number of TUNEL-positive cells per mm(3) (Mann-Whitney test, P=0.04). Double immunocytochemistry for TUNEL and tryptophan hydroxylase (TPH) indicated that DNA fragmentation was prominent in serotonin neurons. These data suggest that in the absence of ovarian steroids, a cascade of gene and protein expression leads to an increase in DNA fragmentation in serotonin neurons. Conversely, ovarian steroids have a neuroprotective role in the non-injured brain and prevent DNA fragmentation and cell death in serotonin neurons of nonhuman primates.Molecular Psychiatry advance online publication, 13 October 2009; doi:10.1038/mp.2009.97.
PMID: 19823180 [PubMed – as supplied by publisher]
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Reproductive hormones tend to be vilified in the politically literature. Thus, the term “ovarian steroids” is used as a euphemism to avoid directly using the words “estrogen” or “progesterone”. Note that estrogen and progesterone are also produced at baseline levels by the adrenal glands and are produced also in males.