Fadao Tai

Effects of neonatal paternal deprivation or early deprivation on anxiety and social behaviors of the adults in mandarin voles

This study examined whether neonatal paternal deprivation (PD: father was removed and pups were raised just by mother) or early deprivation (ED: pups were raised by both parents except separated from not only the dam but also the peers for three hours a day from PND 0 to 13) has long-term effects on anxiety and social behaviors of adult mandarin voles. Newborn mandarin voles of F2 generation were randomly assigned to one of three groups: bi-parental care (PC: pups were raised by both parents), PD and ED. The parental care behaviors of F1 generation were observed at the age of 0, 13 and 21 days (PND 0, 13, 21) of F2 generation of PC and PD groups. Moreover, each mandarin vole of F2 generation received an open field test and a social interaction test on PND 70 and PND 75, respectively. No significant differences of parental behavior were observed between mothers and fathers from PC families, showing typical parental behavior of socially monogamous rodents. In addition, no significant differences of maternal behaviors were found between mothers from PC and PD families, indicating no maternal compensation towards pups for the absence of the paternal care. In the open field test, mandarin voles from both PD and ED families displayed higher levels of anxiety and lower locomotor activity, relative to offspring of PC family. In the social interaction test, both PD and ED mandarin voles also showed lower levels of social behavior and higher levels of anxiety. Thus, both PD and ED significantly increase anxiety and reduce social behavior of adult mandarin voles, suggesting that variation in parental investment may lead to variation in anxiety and social behaviors in rodents with different mating systems.

Sexual or paternal experiences alter alloparental behavior and the central expression of ERα and OT in male mandarin voles (Microtus mandarinus)

Various hypotheses have been proposed to explain factors influencing male alloparental behavior in cooperatively breeding species. Mandarin voles (Microtus mandarinus) are ideal animal models to investigate these factors because they are highly social rodents and display biparental care and spontaneous parental care when exposed to foster pups. Here we test the idea that the sexual and paternal experience of males influences alloparental behavior toward novel pups, and that these experiences alter the expression of neuropeptide oxytocin (OT) and estrogen receptor alpha (ERalpha). Alloparental behavior and OT and ERalpha expression were compared between virgin males that had no prior sexual or reproductive experience, exposed males that with prior exposure to novel pups before the test, paired males that had been housed with a female, and new fathers having their first litter with a female. Our results show that prior exposure to novel pups and prior mating and paternal experience increased male alloparental behavior toward a novel pup. This experience also increased OT expression and affected the expression of ERalpha. This study reveals important initiation factors for male alloparental behavior and suggests a relationship between alloparental behavior and central OT expression in males.

Neonatal paternal deprivation impairs social recognition and alters levels of oxytocin and estrogen receptor α mRNA expression in the MeA and NAcc, and serum oxytocin in mandarin voles

Paternal care is necessary for the healthy development of social behavior in monogamous rodents and social recognition underpins social behavior in these animals. The effects of paternal care on the development of social recognition and underlying neuroendocrine mechanisms, especially the involvement of oxytocin and estrogen pathways, remain poorly understood. We investigated the effects of paternal deprivation (PD: father was removed from neonatal pups and mother alone raised the offspring) on social recognition in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the development of social recognition in female and male offspring according to a habituation-dishabituation paradigm. Paternal deprivation resulted in increased inactivity and reduced investigation during new encounters with other animals. Paternal deprivation reduced oxytocin receptor (OTR) and estrogen receptor α (ERα) mRNA expression in the medial amygdala and nucleus accumbens. Paternal deprivation reduced serum oxytocin (OT) concentration in females, but had no effect on males. Our results provide substantial evidence that paternal deprivation inhibits the development of social recognition in female and male mandarin voles and alters social behavior later in life. This is possibly the result of altered expression of central OTR and ERα and serum OT levels caused by paternal deprivation.

Effects of group housing on stress induced emotional and neuroendocrine alterations

Chronic restraint stress can induce depressive and anxiety-like behavior and neurophysiological disturbances. The social living shows the health-promoting and stress-protective effects on both human and animal. However, whether group housing exerts effects on development of depression and anxiety induced by chronic restraint treatments and its detailed neuroendocrine mechanism remain unclear. Following repeated restraint, the anxiety and depression-like behaviors of single and group housing mice were examined using the elevated plus-maze, open field test and forced swimming test. The levels of central oxytocin (OT) expression in the paraventricular nucleus (PVN), glucocorticoid receptors (GR) in the hippocampus and serum OT and corticosterone (CORT) were also measured using immunohistochemistry and ELISA methods. Our results show that chronic restraint significantly decreased time in open arm of elevated plus maze and increased immobility time in forced swimming test in single-housed mice. However, chronic restraint exerted no effects on these aspects in group-housed mice. Accompanying the changes of behaviors, chronic restraint up-regulated levels of serum CORT and reduced the hippocampus GR in single-housed animals, but did not change these measures in group-housed mice. Furthermore, repeated restraint had no effect on OT levels in these two housing conditions although group-housing significantly increased the PVN OT levels. Taken together, these results provide substantial evidence that group housing can reduce levels of anxiety and depression induced by chronic restraint stress in mice. The elevation of central GR and OT, and decrease of circulating CORT may possibly be involved in these buffering effects.

The effects of neonatal paternal deprivation on pair bonding, NAcc dopamine receptor mRNA expression and serum corticosterone in mandarin voles

High levels of paternal care are important for the development of social behavior in monogamous rodents. However, the effects of paternal care on the formation of pair bonding and underlying neuroendocrine mechanisms, especially the involvements of dopamine system and corticosterone, are not well understood. We investigated effects of paternal deprivation on pair bonding in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the formation of pair bonding in females according to partner preference tests (PPT). Paternal deprivation also reduced body contact behavior and increased aggression in males and females in PPT. During social interaction tests (SIT), paternal deprivation was found to reduce investigative and aggressive behaviors but increase body contact and self-grooming in females, and reduce staring, aggression, body contact and self-grooming in males when interacting with the opposite sex. Paternal deprivation reduced the expression of dopamine 1-type receptor (D1R) mRNA and dopamine 2-type receptor (D2R) mRNA in the nucleus accumbens of female offspring in later life, but enhanced mRNA expression of these two dopamine receptors in males. After three days of cohabitation the expression of D1R mRNA and D2R mRNA was negatively correlated for voles reared by two parents, but positively correlated in paternally deprived animals. Paternal deprivation reduced serum corticosterone levels in females but had the opposite effect in males. Three days of cohabitation did not alter corticosterone levels of PD females, but reduced it in PC females. Our results provide substantial evidence that paternal deprivation inhibits the formation of pair bonding in female mandarin voles and alters social behavior later in life. These behavioral variations were possibly associated with sex-specific alterations in the expression of two types of dopamine receptors and serum corticosterone levels induced by paternal deprivation.

Neonatal paternal deprivation or early deprivation reduces adult parental behavior and central estrogen receptor α expression in mandarin voles (Microtus mandarinus).

Previous studies on parental behavior have primarily focused on maternal behavior, with little research directed at observing paternal behavior. The effects of neonatal paternal deprivation and early deprivation on adult parental behavior and estrogen receptor α (ERα) especially remain unclear. This study examined whether paternal deprivation or early deprivation has long-term effects on the parental behavior and central ERα expression of adult mandarin vole offspring. The parental behaviors of adult mandarin voles that suffered paternal deprivation or early deprivation were observed with their own pups at 0, 13 and 21 days of age. Central ERα expression was also examined in adult virgin voles with different neonatal treatments using immunocytochemistry. The results indicated that (1) levels of parental care and sociability in adult offspring were reduced due to paternal deprivation and early deprivation; (2) ERα expression in the stria terminalis (BNST), medial preoptic area (MPOA), ventromedial hypothalamic nucleus (VMH) and arcuate hypothalamic nucleus (Arc) were also reduced by paternal deprivation and early deprivation; (3) ERα expression in the BNST, MPOA, and VMH of control females was higher than that of control males, but ERα expression in the Arc was lower. Our findings show that paternal care plays an important role in the development of parental behavior in offspring. Also, because paternal deprivation and early deprivation impaired sexual differences, the alteration of parental behavior may be associated with decreased ERα expression.

Pubertal exposure to bisphenol A disrupts behavior in adult C57BL/6J mice.

Bisphenol A (BPA) is a widespread endocrine disrupting chemical that influences adult physiology and behavior after perinatal exposure. However, it is not clear if pubertal exposure to BPA exerts hormone dependent effects on behaviors. Using C57BL/6J mice, we sought to determine how pubertal exposure to BPA affects locomotion, exploration, anxiety and sociability in adulthood. Compared to controls, pubertal exposure to BPA or E(2) (17β-estradiol) significantly altered female exploratory and anxiety behavior. Moreover, BPA and E(2)-treated female mice displayed increased levels of affiliation to female stimulus mice and decreased levels of affiliation to male stimulus mice; while our control males showed affiliation preference to female stimulus. These results indicate that pubertal exposure to BPA or E(2) may masculinize female social and emotional behavior.

Effects of neonatal oxytocin treatment on aggression and neural activities in mandarin voles.

Neonatal manipulation of oxytocin (OT) has long-term effects on behavior and physiology. Here we test the hypothesis that neonatal OT treatment can affect the subsequent expression of intrasexual aggression partly by reprogramming the neural activities of relevant brain regions. To test this hypothesis, mandarin voles (Lasiopodomys mandarinus) received OT or isotonic saline treatment within 24 h of birth. At about 75 days of age, aggressive behaviors and Fos expression in different brain regions were tested. The results indicate that the (1) level of intrasexual aggression was higher and other social contact was lower in SAL-treated sexually naïve males than in females and; (2) OT-treated females showed a greater increase in aggressive behaviors and Fos expression only after exposure to a male than SAL-treated females, but there were no significant changes in aggressive behaviors in males. These results demonstrate a sexual difference in aggression, and that neonatal exposure to OT may increase aggression in female mandarin voles. These effects may be based on changes in neural activities of relevant brain regions including the bed nucleus of the stria terminalis (BNST), lateral septal nucleus (LS), medial preoptic area (MPOA), the paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus (SON), mediodorsal thalamic nucleus (MD), ventromedial nucleus of hypothalamic (VMH), the medial amygdala (MeA) and central amygdala (CeA).

Comparison of sociability, parental care and central estrogen receptor alpha expression between two populations of mandarin voles (Microtus mandarinus)

The socially monogamous mandarin vole (Microtus mandarinus) shows significant behavioral plasticity. We examined whether levels of sociability, parental care and central expression of estrogen receptor alpha differed between two populations with different ecologies. Our results show that males from the Chengcun population display significantly more amicable and less aggressive behaviors towards novel same-sex individuals compared to males from the second population of Xinzheng. Chengcun voles directed more licking behavior towards neonatal pups than did Xinzheng voles. Differences were also found in the number of estrogen receptor alpha-immunoreactive neurons. For example, Xinzheng males displayed significantly higher immunoreactivity than Chengcun males in the medial amygdala, medial preoptic area and ventromedial nucleus of the hypothalamus. Xinzheng females expressed higher levels of estrogen receptor alpha-immunoreactivity than Chengcun females in the medial preoptic area. Chengcun females exhibited significantly more estrogen receptor alpha expression than Xinzheng females in the bed nucleus of the stria terminalis. Our results indicate that mandarin voles from the Chengcun site possess monogamous traits, and animals from Xinzheng possess polygamous traits. It also appears that different social behavior and levels of parental care in these two populations may be associated with differences in estrogen receptor alpha-immunoreactive neurons.

Sociality and oxytocin and vasopressin in the brain of male and female dominant and subordinate mandarin voles.

The dominant–subordinate hierarchy in animals often needs to be established via agonistic encounters and consequently affects reproduction and survival. Differences in brain neuropeptides and sociality among dominant and subordinate males and females remain poorly understood. Here we explore neuropeptide levels and sociality during agonistic encounter tests in mandarin voles. We found that dominant mandarin voles engaged in higher levels of approaching, investigating, self-grooming and exploring behavior than subordinates. Dominant males habituated better to a stimulus vole than dominant females. Dominant males displayed significantly less oxytocin-immunoreactive neurons in the paraventricular nuclei and more vasopressin-immunoreactive neurons in the paraventricular nuclei, supraoptic nuclei, and the lateral and anterior hypothalamus than subordinates. Dominant females displayed significantly more vasopressin-immunoreactive neurons in the lateral hypothalamus and anterior hypothalamus than subordinates. Sex differences were found in the level of oxytocin and vasopressin. These results indicate that distinct parameters related to central nervous oxytocin and vasopressin are associated with behaviors during agonistic encounters in a sex-specific manner in mandarin voles.