Effects of treadmill exercise on anxiety-like behavior in association with changes in estrogen receptors ERα, ERß and oxytocin of C57BL/6J female mice.

Exercise can reduce the incidence of stress-related mental diseases, such as depression and anxiety. Control group was neither exposed to CVMS nor TRE (noCVMS/noTRE). Females were tested and levels of serum17-beta-oestradiol (E2), estrogen receptors α immunoreactive neurons (ERα-IRs), estrogen receptors ß immunoreactive neurons (ERß-IRs) and oxytocin immunoreactive neurons (OT-IRs) were measured. The results showed there's increased anxiety-like behaviors for mice from CVMS/noTRE, CVMS/higher speed TRE (CVMS/HTRE) and noCVMS/HTRE groups when they were put in open field and elevated maze tests. They had lower serum E2 levels than mice from CVMS/low-moderate speed TRE (CVMS/LMTRE), noCVMS/LMTRE and noCVMS/noTRE groups. The three groups of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice had more ERα-IRs and less ERß-IRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of OT-IRs in PVN and SON of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice was also lower than that of mice from CVMS/LMTRE, noCVMS/LMTRE and noCVMS/noTRE groups. Interestingly, CVMS/LMTRE and noCVMS/LMTRE mice were similar to noCVMS/noTRE mice in that they did not show anxiety, while CVMS/HTRE and noCVMS/HTRE mice did not, which were similar to the mice in CVMS/noTRE. We propose that LMTRE instead of HTRE changes the serum concentration of E2. ERß/ERα ratio and OT level in the brain may be responsible for the decrease in anxiety-like behavior in female mice exposed to anxiety-inducing stress conditions.

Estradiol Treatment during Perinatal Development Alters Adult Partner Preference, Mating Behavior and Estrogen Receptors α and ß in the Female Mandarin Vole (Microtus mandarinus).

During development, many aspects of behavior, including partner preferences and sexual conduct, are "organized" by estradiol. This study aimed at analyze these processes in the mandarin vole (Microtus mandarinus), a novel experimental mammal with strong monogamous pair bonds. Female pups were treated daily with an oil vehicle (FC) or ß-Estradiol (E2, FT) from prenatal day 14 to postnatal day 10. Male pups were treated daily with the oil vehicle only (MC). Partner preferences, sexual conduct and the expression of estrogen receptors α (ERα) and ß (ERß) were examined when animals were 3 months old. FT and MC groups showed female-directed partner preferences and masculinized behavior. ERα- immunoreactive neurons (ERα-IRs) in the bed nucleus of stria terminalis (BNST) and medial amygdaloid nucleus (MeA) was greater in FT females than MC males, and there was no significant difference in the number of ERα-IRs between FT and FC females. No difference was found for ERα-IRs in the preoptic area (mPOA) or ventromedial nucleus of the hypothalamus (VMH) of FT females or MC males, and they were significantly fewer than in FC females. ERß-immunoreactive neurons (ERß-IRs) in these four brain regions did not alter the ERß/ERα ratio in different brain regions during perintal developments. However, the number of ERß-IRs in FT females and MC males were greater than in FC females. We propose that estradiol treatment during perinatal development is responsible for adult partner preferences and mating behavior.

Perinatal stress effects on later anxiety and hormone secretion in male mandarin voles.

The estradiol (E2), estrogen receptor-α (ERα), testosterone (T), and androgen receptor (AR) can contribute to anxiety, but whether they are associated with the reversion of prenatal adverse outcomes remains unclear. Here, we tested the interactive effects of prenatal maternal restraint stress and early postnatal short-term maternal separation on adult male mandarin vole (Microtus mandarinus) behavior and changes in E2, T, and their receptors. The results showed that PS adult males (PS/NH) exhibited an increase in anxiety-like behavior in open-field and elevated plus-maze tests than the other 3 groups, including adult male offspring controls (PC/NH), adult male offspring controls with short-term maternal separation (PC/H), and PS adult males with short-term maternal separation (PS/H). The increase in anxiety-like behavior was associated with significantly lower E2 and T serum levels, had significantly more ERα immunoreactive neurons (ERα-IRs) in some brain regions, as well as significantly fewer AR immunoreactive neurons (AR-IRs) in some brain regions than the other 3 groups. We found it interesting that the PC/H and PS/H were similar to the PC/NH in that they did not produce anxiety-like behavior. However, early postnatal short-term maternal separation reversed prenatally induced changes in E2 and T serum levels and altered ERα-IRs and AR-IRs in the brain. These data suggest that changes in anxious adults may be governed by early environmental factors and their interactions because changes in E2 and T serum levels and the distribution of ERα and AR in the brain result in behavioral changes related to less anxiety into adulthood.

[Perinatal clomiphene citrate treatment changes sexual orientations of male mice].

Perinatal period and adolescence are critical for brain development, which is the biological basis of an individual's sexual orientation and sexual behavior. In this study, animals were divided into two groups and their sexual orientations were observed: one group experienced drug treatments during the perinatal period, and the other group was castrated at puberty. The results showed that estradiol treatment had no effect on mature male offspring's sexual orientations, but 9 days and 14 days of clomiphene citrate treatment significantly increased the chance of homosexuality and effeminized behavior. In addition, the sexual orientation of mature normal male offspring, which were castrated when they were 21 days old,was not significant different from the control animals. These findings suggest that the inhibition of perinatal estrogen activities could suppress individual male-typical responses, enhance female-typical responses and induce homosexual orientations. Moreover, the masculinizing effects of estrogen were more obvious during perinatal period than adolescence.