Development of the Paternal Brain in Humans throughout Pregnancy.

Previous studies have demonstrated that paternal caregiving behaviors are reliant on neural pathways similar to those supporting maternal care. Interestingly, a greater variability exists in parental phenotypes in men than in women among individuals and mammalian species. However, less is known about when or how such variability emerges in men. We investigated the longitudinal changes in the neural, hormonal, and psychological bases of expression of paternal caregiving in humans throughout pregnancy and the first 4 months of the postnatal period. We measured oxytocin and testosterone, paternity-related psychological traits, and neural response to infant-interaction videos using fMRI in first-time fathers and childless men at three time points (early to mid-pregnancy, late pregnancy, and postnatal). We found that paternal-specific brain activity in prefrontal areas distinctly develops during middle-to-late pregnancy and is enhanced in the postnatal period. In addition, among fathers, the timing of the development of prefrontal brain activity was associated with specific parenting phenotypes.

Development of the paternal brain in expectant fathers during early pregnancy.

The human parenting brain network mediates caregiving behaviors. When exposed to the stimuli of their infants, compared with non-parents, both fathers and mothers exhibit distinct patterns of neural activation. As human males, relative to females, do not undergo robust physiological changes during pregnancy, when and how the paternal brain networks begin to form remains unclear. Thus, using functional MRI, we examined brain activation in response to infant-interaction videos in two groups, childless males and first-time expectant fathers during their partners' early pregnancy before remarkable changes in their partners' appearances commenced. Multivoxel pattern analysis revealed that expectant fathers' left anterior insula and inferior frontal gyrus showed incipient changes in response to parenthood during early pregnancy. Furthermore, these changes were associated with several paternal traits, such as a negative image toward parenting. Such external factors might influence the paternal brain's development during early pregnancy.

Basal cortisol concentrations related to maternal behavior during puppy development predict post-growth resilience in dogs.

A prolonged stress hyporesponsive period (SHRP) due to the mother's presence may delay the timing of glucocorticoid (GC) elevation in infants, thereby reducing the excessive stress response that would affect post-growth temperament. In dogs, the SHRP has been suggested to persist until postnatal week (PW) 4; therefore, PW 5, which SHRP may be prolonged by the mother dog, may be a critical point in the developmental stage of dogs to establish stress responsiveness. We conducted a long-term survey on the development of dogs to investigate i) whether the degree of the stress response at PW 5 is determined by maternal behavior and ii) whether it can predict post-growth stress responses and temperament in dogs. As a result, the offspring of mother dogs who had more delivery experience and exhibited more maternal behavior showed higher basal cortisol concentrations at PW 5. These offspring may have acquired less fear response as an individual trait and had relatively quick adaptability, albeit with high cortisol concentrations during exposure to novel environments post-growth, suggesting that high cortisol concentrations at PW 5 are linked to resilience post-growth. Basal cortisol concentrations at PW 7 were not affected by maternal variables and were not associated with cortisol response to novel environments post-growth. GCs are essential hormones that increase the probability of survival. Therefore, the high hypothalamic pituitary adrenal activities of the mother dogs and their offspring in this study may not immediately indicate negative states, and these results prompt a reconsideration of the role of GC in organisms.

Testosterone regulates the emission of ultrasonic vocalizations and mounting behavior during different developmental periods in mice.

Testosterone masculinizes male sexual behavior by providing organizational and activational effects during the perinatal and peripubertal periods and during adulthood, respectively. We revealed that the emission of ultrasonic vocalizations (USVs) and mounting behavior was regulated by different neural circuits. However, the detailed testosterone effects on these two behaviors have not been fully elucidated. Here, we evaluated the time-dependent effects of testosterone on USVs and mounting behavior in mice using a testosterone treatment model, in which females were treated with testosterone to assess the "gain-of-function" and a "loss-of-function" model. In the loss-of-function model, we used Ad4BP/SF-1ΔFLC/- male mice, in which testosterone production was abolished in prenatal and postnatal stages, and Ad4BP/SF-1ΔFLC/ΔFLC mice, in which testosterone production was markedly reduced only in prenatal stages. When testosterone was administered to female mice during the neonatal and peripubertal periods, but not during adulthood, USV emissions increased. Conversely, testosterone treatment in adult female mice increased the mounting behavior, but not USVs. In Ad4BP/SF-1ΔFLC/- mice, USVs and mounting behavior was completely absent. Ad4BP/SF-1ΔFLC/ΔFLC male mice displayed equivalent levels of USVs but less mounting behavior. Collectively, these results suggest that testosterone has dual regulatory roles in USV emissions and mounting behavior.

Breastfeeding dynamically changes endogenous oxytocin levels and emotion recognition in mothers.

Breastfeeding behaviours can significantly change mothers' physiological and psychological states. The hormone oxytocin may mediate breastfeeding and mothers' emotion recognition. This study examined the effects of endogenous oxytocin fluctuation via breastfeeding on emotion recognition in 51 primiparous mothers. Saliva oxytocin was assessed before and after the manipulation (breastfeeding or holding an infant), and emotion recognition tasks were conducted. Among mothers who breastfed daily, mothers with more increased levels of oxytocin after breastfeeding showed more reduced negative recognition and enhanced positive recognition of adult facial expressions. These oxytocin functions accompanying breastfeeding may support continued nurturing behaviours and also affect the general social cognition of other adults beyond any specific effect on infants.

Effect of Canine Oxytocin Receptor Gene Polymorphism on the Successful Training of Drug Detection Dogs.

Drug detection dogs can be trained to locate various prohibited drugs with targeted odors, and they play an important role in the interdiction of drug smuggling in human society. Recent studies provide the interesting hypothesis that the oxytocin system serves as a biological basis for co-evolution between dogs and humans. Here, we offer the new possibility that genetic variation of the canine oxytocin receptor (OXTR) gene may regulate the success of a dog's training to become a drug detection dog. A total of 340 Labrador Retriever dogs that were trained to be drug detection dogs in Japan were analyzed. We genotyped an exonic SNP (rs8679682) in the OXTR gene and compared the training success rate of dogs with different genotypes. We also asked dog trainers in the training facility to evaluate subjective personality assessment scores for each dog and examined how each dog's training success was related to those scores. A significant effect of the OXTR genotype on the success of the dogs' training was found, with a higher proportion of dogs carrying the C allele (T/C and C/C genotypes) being successful candidates than dogs carrying the T/T genotype. Dog personality scores of Training Focus (Factor 1) were positively correlated with an increased likelihood that a dog would successfully complete training. Although the molecular mechanism of the OXTR gene and its functional pathway related to dog behavior remains unknown, our findings suggest that canine OXTR gene variants may regulate individual differences between dogs in their responsiveness to training for drug detection.

Oxytocin promotes social bonding in dogs.

Recent evidence suggests that enduring social bonds have fitness benefits. However, very little is known about the neural circuitry and neurochemistry underlying the formation and maintenance of stable social bonds outside reproductive contexts. Oxytocin (OT), a neuropeptide synthetized by the hypothalamus in mammals, regulates many complex forms of social behavior and cognition in both human and nonhuman animals. Animal research, however, has concentrated on monogamous mammals, and it remains unknown whether OT also modulates social bonds in nonreproductive contexts. In this study we provide behavioral evidence that exogenous OT promotes positive social behaviors in the domestic dog toward not only conspecifics but also human partners. Specifically, when sprayed with OT, dogs showed higher social orientation and affiliation toward their owners and higher affiliation and approach behaviors toward dog partners than when sprayed with placebo. Additionally, the exchange of socio-positive behaviors with dog partners triggered the release of endogenous OT, highlighting the involvement of OT in the development of social relationships in the domestic dog. These data provide new insight into the mechanisms that facilitate the maintenance of close social bonds beyond immediate reproductive interest or genetic ties and complement a growing body of evidence that identifies OT as one of the neurochemical foundations of sociality in mammalian species.

Early weaning impairs fear extinction and decreases brain-derived neurotrophic factor expression in the prefrontal cortex of adult male C57BL/6 mice.

We examined the developmental effects of early weaning on anxiety and the extinction of fear memory in male C57BL/6 mice. Early weaning led to increased freezing behaviors after fear conditioning via the foot-shock method both during extinction training and in a test of extinction recall, but did not induce significant changes in anxiety-like behavior. In addition, we found that the levels of brain-derived neurotrophic factor (BDNF) protein and mRNA transcripts for BDNF exon III in the medial prefrontal cortex (mPFC) at the time of extinction recall were impaired in early-weaned mice compared to normally weaned mice. In light of consistent finding that early-weaned mice experience greater stress at weaning, these data suggest that early weaning of male C57BL/6 mice is valuable for studies of the pathogenesis of post-traumatic stress disorder.

Early weaning impairs a social contagion of pain-related stretching behavior in mice.

Pain sensitivity in mice can be modulated through exposure to familiar individuals. This phenomenon is considered a form of emotional contagion, thought to be an evolutionary precursor of empathy in mammals. In particular, mother-infant interactions early in life can considerably alter empathy development. Here, we demonstrated that pairs of mice that were simultaneously administered with a noxious stimulus (acetic acid) exhibited more pain-related behaviors than when one of the pair was treated with a noxious stimulus. However, these differences disappeared when mice were separated from the dam 1 week earlier than the typical weaning age. Even when mice were alone, when treated with acetic acid, early weaning decreased their pain response. These results suggested that the disruption of mother-infant bonding through early weaning impairs pain contagion and modulates sensitivity to pain.

The behavioral and endocrinological development of stress response in dogs.

Endocrinological stress response has been shown to be absent in a specific period of the early life of rodents; this is named the stress-hyporesponsive period (SHRP). The SHRP is a significant period for the appropriate development of infants. In this study, the presence of SHRP in dogs was identified by conducting a 5-min separation test in 142 Labrador retriever puppies in their early socialization period and measuring the changes in urinary cortisol levels. An increase in cortisol after separation was found after 5 weeks of age, suggesting that the SHRP persists until 4 weeks of age in dogs. The distress vocalization during separation changed and the lactating behavior decreased rapidly around 5 weeks of age, suggesting that the endocrinological and emotional aspects of development change at approximately 5 weeks of age and maternal inhibition of cortisol might occur in dogs as well as rodents.

Attachment-like behavioral expressions to humans in puppies are related to oxytocin and cortisol: A comparative study of Akitas and Labrador Retrievers.

This study investigated the relationship between urinary hormone concentrations and attachment-related behaviors in two dog breeds, the Akitas and Labrador Retrievers, to elucidate the hormonal and behavioral mechanisms underlying domestication and interspecies attachment to humans. By measuring cortisol and oxytocin concentrations, and conducting the Strange Situation Test (SST), we aimed to investigate breed differences in endocrine secretions associated with domestication and how these differences influence dog behavior toward humans. Our results showed significant breed differences in urinary cortisol concentrations, with Akitas exhibiting higher levels than Labrador Retrievers. This suggests a breed-specific stress response related to genetic proximity to wolves. However, oxytocin concentrations did not differ significantly, which suggests a complex interplay between factors influencing the domestication process and the formation of attachment behaviors. Behavioral observations during the SST revealed breed-specific patterns, with Labrador Retrievers showing more playful and attachment-like behaviors and Akitas showing more exploratory and passive behaviors. The study found correlations between hormones and behaviors within breeds, particularly in Labrador Retrievers, where oxytocin concentrations were associated with attachment-like behaviors, and cortisol concentrations reflected individual differences in physical activity rather than stress responses to social situations. These findings contribute to the understanding of the evolutionary and adaptive processes underlying the ability of domestic dogs to form close relationships with humans while highlighting the role of hormonal mechanisms in mediating attachment behaviors and the influence of breed-specific genetic backgrounds on these processes.

Intestinal microbiome and maternal mental health: preventing parental stress and enhancing resilience in mothers.

The number of mothers suffering from mental illness is increasing steadily, particularly under conditions of the coronavirus pandemic. The identification of factors that contribute to resilience in mothers is urgently needed to decrease the risks of poor physical and psychological health. We focused on the risk of parenting stress and psychological resilience in healthy mothers with no psychiatric and physical disorders and conducted two studies to examine the relationships between intestinal microbiota, physical condition, and psychological state. Our results showed that alpha diversity and beta diversity of the microbiome are related to high parenting stress risk. Psychological resilience and physical conditions were associated with relative abundances of the genera Blautia, Clostridium, and Eggerthella. This study helps further understand the gut-brain axis mechanisms and supports proposals for enhancing resilience in mothers.

Beacon-based sleep-wake monitoring in dogs.

The sleep-wake cycle represents a crucial physiological process essential for maintaining homeostasis and promoting individual growth. In dogs, alterations in sleep patterns associated with age and dog's correlation with temperament factors, such as nervousness, have been reported, and there is an increasing demand for precise monitoring of sleep and physical activity in dogs. The present study aims to develop an analysis method for measuring sleep-wake patterns and physical activity in dogs by utilizing an accelerometer and a smartphone. By analyzing time series data collected from the accelerometer attached to the dog's collar, a comprehensive sleep and activity analysis model was constructed. This model classified the activity level into seven classes and effectively highlighted the variations in sleep-activity patterns. Two classes with lower activity levels were considered as sleep, while other five levels were regarded as wake based on the rate of occurrence. This protocol of data acquisition and analysis provides a methodology that enables accurate and extended evaluation of both sleep and physical activity in dogs.

Modulation of gut microbiota composition due to early weaning stress induces depressive behavior during the juvenile period in mice.

BACKGROUND: The gut microbiota plays an important role in the development of behavior and immunity in infants and juveniles. Early weaning (EW), a form of social stress in mice, leads to increased anxiety and an enhanced stress response in the hypothalamic-pituitary-adrenal axis during adulthood. Early life stress also modulates the immune system and increases vulnerability to infection. However, studies investigating the causal relationships among juvenile stress, microbiota changes, and immune and behavioral deficits are limited. Therefore, we hypothesized that EW alters gut microbiota composition and impairs the development of the nervous and immune systems. RESULTS: EW mice moved longer distances in the marble-burying test and had longer immobility times in the tail suspension test than normal weaning (NW) mice. In parallel, the gut microbiome composition differed between NW and EW mice, and the abundance of Erysipelotrichacea in EW mice at 8 weeks of age was lower than that in NW mice. In an empirical study, germ-free mice colonized with the gut microbiota of EW mice (GF-EW mice) demonstrated higher depressive behavior than GF mice colonized with normal weaning microbiota (GF-NW mice). Immune cell profiles were also affected by the EW microbiota colonization; the number of CD4 + T cells in the spleen was reduced in GF-EW mice. CONCLUSION: Our results suggest that EW-induced alterations in the gut microbiota cause depressive behaviors and modulate the immune system.

Organizational effects of estrogen on male-type vulnerability to early weaning.

We previously reported that early-weaned (postnatal day 14) male ICR mice, compared to normally weaned animals, exhibited a persistent increase in anxiety-related behavior in the elevated plus maze test. In this study, we examined whether steroid hormone manipulations on postnatal day 0 and at the ages of 2 or 3 weeks affected male-type vulnerability to early weaning. Neither castration nor ovariectomy at the age of 3 weeks affected male-type vulnerability. However, in males, castration at the age of 2 weeks attenuated the increased anxiety levels induced by early weaning, and the implantation of testosterone or estradiol, but not of dihydrotestosterone, restored the effects of early weaning. In contrast, in females, neonatal treatment with testosterone propionate together with testosterone at the age of 2 weeks, which reversed sexual behavior to the male type, did not affect anxiety levels in response to early weaning. When pregnant females were repeatedly treated with testosterone propionate on embryonic days 14, 17, and 19, in addition to testosterone treatment at the age of 2 weeks, the anxiety levels in female were increased by early weaning. Furthermore, the prenatal treatment of estradiol benzoate, but not dihydrotestosterone, induced enhanced anxiety levels by early weaning in females. These results suggest that neural systems are masculinized by estrogen from the embryonic phase to the early postnatal period and are responsible for the high levels of anxiety elicited by early weaning.

Ownership of dogs and cats leads to higher levels of well-being and general trust through family involvement in late adolescence.

Introduction: Late adolescence is a crucial period during which individuals connect with new communities. Furthermore, their mental health has lasting effects on their overall well-being. Involvement with family and the local community plays a significant role in shaping adolescents' personalities and well-being. Additionally, pets, such as dogs and cats, function as social catalysts and increase interactions with family and the local community. We hypothesized that pet ownership would increase involvement with family and the local community and thereby impact adolescents' personalities and well-being. Methods: Therefore, this study investigated whether owning dogs or cats was related to well-being through increased involvement with family and local community members in late adolescence. Data were collected via a questionnaire administered to high school and university students. The questionnaire included questions on basic information about adolescents and their families, pet ownership experience, family and local community involvement, well-being, cultural estrangement inventory, and general trust. Results: Structural equation modeling revealed that adolescent women who owned dogs or cats had higher well-being and general trust through their involvement with their families. Although previous research reported that men who had experienced pet ownership in childhood were more sociable in old age, the effect of pet ownership on men was not observed in this study. Discussion: During late adolescence, when individuals experience many connections with new communities, the effects of pets may temporarily decrease. Therefore, future cohort studies should examine the effects of pets on each age group.

Dogs showed lower parasympathetic activity during mutual gazing while owners did not.

The affiliative relationship between humans and dogs is compared to a mother-infant attachment relationship. We hypothesized that dog's attachment behavior in negative emotional state aroused the owner's attention toward the dog, that is, reduced parasympathetic activity. We measured heart rate variability in both dogs and humans during the Strange Situation Test to examine whether the owners' parasympathetic activity was decreased by being gazed at by their dogs. Our results in a short-term of 6 s before and after the moment the dog gazed at the human face indicated that dogs' parasympathetic activity was lower when the dogs were gazing at their owners than when it was gazing at unfamiliar persons. Dog's autonomic activity was also lower when the dogs were living with their owners for a longer period. However, we could not determine whether gaze from the dog affected the autonomic activity in humans as attachment behavior.

Effects of the COVID-19 Pandemic on the Behavioural Tendencies of Cats and Dogs in Japan.

Physical and mental effects stemming from COVID-19 have impacted not only people's lives but also the lives of their pets, which in recent years are often seen as members of the family. This study aimed to explore the impact of the COVID-19 pandemic in Japan on pets and their owners. Participants reported changes in physical activity and mental health, as well as working conditions and frequency of interaction with pets, before and after behavioural restrictions due to the COVID-19 pandemic. We also asked about their pets' behaviours using the Feline Behavioural Assessment and Research Questionnaire (Fe-BARQ) and the Canine Behavioural Assessment and Research Questionnaire (C-BARQ). This study showed that most cat and dog owners spent more time at home due to the COVID-19 behavioural restrictions and that the frequency of contact interaction with their pets increased. However, this study showed higher stress-related behaviours (e.g., cats: excessive grooming; dogs: aggression towards owners) among pets whose owners increased contact interaction. Furthermore, owners' low mental health was correlated with high stress-related behaviours (e.g., touch sensitivity) in pets. The results of this study indicate that the lockdown caused by the COVID-19 pandemic in Japan may have affected not only the lives of owners but also the interaction between owners and their pets, and consequently their pets' behaviours. Therefore, there is also concern that changes in lifestyle patterns caused by pandemics could form a negative feedback loop between the health status of both owners and their pets.

N-acetylmannosamine improves object recognition and hippocampal cell proliferation in middle-aged mice.

Sialic acids may modulate cell proliferation and gene expression, particularly in neural cells in vitro. However, the function of sialic acids in the central nervous system has not previously been examined. We examined whether N-acetylmannosamine (ManNAc) could improve object recognition and hippocampal cell proliferations in middle-aged mice. C56BL/6J mice aged 52 weeks were treated with ManNAc for 4 weeks. Their cognitive-ability was assessed with a place and object recognition test. ManNAc, but not N-acetylglucosamine or N-acetylneuraminic acid, improved the index score in the place recognition task at a dosage of 5.0 mg/mL in drinking water. Additionally, ManNAc enhanced the hippocampal cell proliferation, which was evaluated by a bromodeoxyuridine assay and the number of Ki67-immunoreactive cells. We could demonstrate that ManNAc had positive effects on the age-related brain dysfunction. These findings suggest that the use of ManNAc or related compounds may be a new approach for the treatment of human dementia.

Neuroendocrine Mechanisms of Social Bonds and Separation Stress in Rodents, Dogs, and Other Species.

Mammalian species form unique bonds between mothers and infants. Maternal care, including suckling, is necessary for infant survival, and the mother and, sometimes, the father require a lot of effort in nurturing infants. An infant's probability of survival depends on the extent of the investment of care by the mother. In parallel, mothers must identify their offspring and invest only in those who possess their genes to achieve evolutionary benefits. Therefore, they need to recognize their offspring and show a strong preference for them. For this reason, bond formation between mothers and infants is important. The mother monitors her offspring's physical condition and stays close to them. The offspring also form strong bonds with their mothers. Therefore, a separation between the mother and infant causes severe stress for both parties. Although it was initially thought that such bonds between mother and infant are limited to the same species, we have also observed a similar phenomenon in the human-dog relationship. In this article, we discuss the neuroendocrine mechanisms that underlie bond formation and separation based on findings of neurobiological research in mice and the relationship between humans and dogs.