Ovarian steroids decrease DNA fragmentation in the serotonin neurons of non-injured rhesus macaques.

Area of Science:

• Neuroscience
• Endocrinology
• Cell Biology

Background:

• Ovarian steroids are known to promote neuroprotection in serotonin neurons.
• This neuroprotection involves decreasing pro-apoptotic gene and protein expression in the dorsal raphe nucleus.
• The current study investigates if these effects extend to reducing DNA fragmentation.

Purpose of the Study:

• To determine if ovarian steroids reduce DNA fragmentation in serotonin neurons.
• To investigate the neuroprotective role of estradiol and progesterone in the non-injured brain.

Main Methods:

• Ovariectomized rhesus monkeys were treated with placebo, estradiol (E), progesterone (P), or E+P.
• The terminal deoxynucleotidyl transferase nick end labeling (TUNEL) method was used to detect DNA fragmentation.
• TUNEL-positive cells in the dorsal raphe nucleus were quantified using stereology.

Main Results:

• Progesterone (P) and estradiol + progesterone (E+P) treatments significantly reduced the total number of TUNEL-positive cells compared to controls.
• Estradiol + progesterone (E+P) treatment significantly reduced the density of TUNEL-positive cells (cells per mm³).
• Double immunocytochemistry confirmed that DNA fragmentation occurred in serotonin neurons (identified by tryptophan hydroxylase).

Conclusions:

• Ovarian steroids play a crucial neuroprotective role in the non-injured brain.
• These steroids prevent DNA fragmentation and cell death in serotonin neurons.
• The absence of ovarian steroids leads to increased DNA fragmentation in serotonin neurons via gene and protein expression cascades.