Abstract
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 (EP) 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 EP treatment significantly reduced the total number of TUNEL-positive cells (Mann-Whitney test, both treatments P=0.04) and EP treatment reduced the number of TUNEL-positive cells per mm3 (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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 657-668 |
| Number of pages | 12 |
| Journal | Molecular Psychiatry |
| Volume | 15 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2010 |
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Keywords
- Apoptosis
- Dorsal raphe nucleus
- Estrogen
- Progesterone
- Serotonin
- TUNEL
ASJC Scopus subject areas
- Molecular Biology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
Cite this
Ovarian steroids decrease DNA fragmentation in the serotonin neurons of non-injured rhesus macaques. / Lima, F. B.; Bethea, Cynthia.
In: Molecular Psychiatry, Vol. 15, No. 6, 06.2010, p. 657-668.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ovarian steroids decrease DNA fragmentation in the serotonin neurons of non-injured rhesus macaques
AU - Lima, F. B.
AU - Bethea, Cynthia
PY - 2010/6
Y1 - 2010/6
N2 - 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 (EP) 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 EP treatment significantly reduced the total number of TUNEL-positive cells (Mann-Whitney test, both treatments P=0.04) and EP treatment reduced the number of TUNEL-positive cells per mm3 (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.
AB - 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 (EP) 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 EP treatment significantly reduced the total number of TUNEL-positive cells (Mann-Whitney test, both treatments P=0.04) and EP treatment reduced the number of TUNEL-positive cells per mm3 (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.
KW - Apoptosis
KW - Dorsal raphe nucleus
KW - Estrogen
KW - Progesterone
KW - Serotonin
KW - TUNEL
UR - http://www.scopus.com/inward/record.url?scp=77952886325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952886325&partnerID=8YFLogxK
U2 - 10.1038/mp.2009.97
DO - 10.1038/mp.2009.97
M3 - Article
VL - 15
SP - 657
EP - 668
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 6
ER -