Estradiol suppresses neuronal firing activity and c-Fos expression in the lateral habenula.

ABSTRACT

Estradiol is an ovarian steroid hormone that regulates physiological functions in the central nervous system, including mood, cognition, sleep and mental state. Emerging evidence has revealed that there is an enrichment of cells that express the estrogen receptor in the lateral habenula (LHb) region, however, the precise biological functions of estradiol on neurons in the LHb remain to be elucidated. The present study aimed to determine the effects of estradiol on LHb neurons, by observing neuronal firing activity, and c­Fos mRNA and protein expression levels in the LHb using whole cell recording, reverse transcription­quantitative polymerase chain reaction and western blotting. Ovariectomized female Wistar rats were supplemented with a range of estradiol doses across five groups Ovariectomized (no treatment); Oil (sesame oil); low estradiol; medial estradiol (ME) and high estradiol. Circulating serum estradiol levels were assessed over a 33 day period following surgery. Estradiol suppressed spontaneous firing activity in LHb neurons (P<0.05, compared with firing rates prior to estradiol treatment), which suggested a role for this hormone in regulating neuronal activity. Estradiol replacement therapy resulted in sustained serum estradiol levels for ~3 weeks after surgery. The mRNA and protein levels of c­Fos were significantly downregulated in LHb tissues from ME rats as compared with Oil animals (P<0.05). In conclusion, the present study demonstrated that estradiol suppresses neuronal activities in the LHb region, suggesting that the LHb may be a potential target for estradiol action.