Sachiko Koyama

• Ph.D.
• Indiana University School of Medicine - Lafayette

The current understanding of the activity of mammalian pheromones is that endocrine and behavioural effects are limited to the exposed individuals. Here, we demonstrate that the nasal exposure of female mice to a male murine pheromone stimulates expansion of mammary glands, leading to prolonged nursing of pups. Subsequent behavioural testing of the...

Enhancement of adult neurogenesis in female mice was previously demonstrated through exposure to soiled bedding from males, although the identity of relevant chemosignals has remained unknown. The farnesenes and SBT (2-sec-butyl-4,5-dihydrothiazole) are male murine pheromones that dominant males secrete at higher levels. Previous studies have shown...

Adult neurogenesis in female mice is known to be enhanced by exposure to soiled bedding from males, although the identity of the relevant chemosignals has remained unknown. Here we show that the previously recognized male murine pheromones, the farnesenes and 2-sec-butyl-4,5-dihydrothiazole (SBT), strongly increase cell proliferation in the subvent...

The correlation between social status and sperm motility of mice was investigated. From 5 to 15 weeks of age, mice were kept under two housing conditions, i.e., in pairs or in isolation. The social dominance in the paired mice was determined with the resident-intruder tests, which were carried out from 8 to 15 weeks of age. At the end of 15 weeks o...

Half a century has passed since the first report of the influence of odors on mice. Odors are known to influence behavior (signaling effect) and affect the physiology (primer effect) of mice. This review focuses on summarizing the primer effects found so far in female and male mice. Odors from conspecifics of the opposite sex had the tendency to en...

Drug interactions are major causes of interindividual variability in tacrolimus exposure and effect. Tacrolimus, a widely used drug in transplant patients, is metabolized by CYP3A4 and CYP3A5. Cannabidiol (CBD) use after transplant is common. Clinical cases suggest CBD may alter tacrolimus exposure, but the mechanism of this interaction is unknown....

Cannabidiol (CBD) is one of the major phytochemical constituents of cannabis, Cannabis sativa, widely recognized for its therapeutic potential. While cannabis has been utilized for medicinal purposes since ancient times, its psychoactive and addictive properties led to its prohibition in 1937, with only the medical use being reauthorized in 1998. U...

One in six Americans uses cannabidiol‐based or cannabis‐derived products. Cannabidiol is a substrate of CYP3A, but its role as a potential CYP3A inhibitor remains unclear. We hypothesized that cannabidiol would inhibit CYP3A‐mediated metabolism of tacrolimus. This report is an interim analysis of an open‐label, three‐period, fixed‐sequence, crossov...

Organ and tissue damage can result from injury and disease. How to facilitate regeneration from damage has been a topic for centuries, and still, we are trying to find agents to use for treatments. Two groups of biological substances are known to facilitate wound healing. Phytochemicals with bioactive properties form one group. Many phytochemicals...

Introduction There have been large geographical differences in the infection and death rates of COVID-19. Foods and beverages containing high amounts of phytochemicals with bioactive properties were suggested to prevent contracting and to facilitate recovery from COVID-19. The goal of our study was to determine the correlation of the type of foods/...

Background Smell disorders are commonly reported with COVID-19 infection. The smell-related issues associated with COVID-19 may be prolonged, even after the respiratory symptoms are resolved. These smell dysfunctions can range from anosmia (complete loss of smell) or hyposmia (reduced sense of smell) to parosmia (smells perceived differently) or ph...

BACKGROUND: One in seven Americans use cannabidiol-based or cannabis-derived products. The FDA drug label for cannabidiol (EPIDIOLEX®; Greenwich Biosciences, Carlsbad, CA) indicates the drug is a substrate of CYP3A, but not an inhibitor. We hypothesized that cannabidiol would inhibit CYP3A-mediated metabolism of tacrolimus (PROGRAF®; Astellas Pharm...

Purpose There have been large geographical differences in the infection and death rates of COVID-19. Foods and beverages containing high amounts of phytochemicals with bioactive properties were suggested to prevent contracting, to limit the severity of, and to facilitate recovery from COVID-19. The goal of our study was to determine the correlation...

Background and Hypothesis: PPARγ is a nuclear receptor expressed in most cells of the body and exerts metabolic function, including adipocyte differentiation and insulin sensitization. This mechanism is termed transactivation, where ligand binding leads to transcription of target genes. However, PPARγ also has a transrepression activity, where liga...

BACKGROUND Smell disorders are commonly reported with COVID-19 infection. The smell-related issues associated with COVID-19 may be prolonged, even after the respiratory symptoms are resolved. These smell dysfunctions can range from anosmia (complete loss of smell) or hyposmia (reduced sense of smell) to parosmia (smells perceived differently) or ph...

Smell disorders are commonly reported with COVID-19 infection. Some patients show prolonged smell-related issues, even after the respiratory symptoms are resolved. To explore the concerns of patients, and to provide an overview for each specific smell disorder, we explored the longitudinal survey that was conducted by 1, and contained self-reports...

Background Sudden chemosensory changes were considered an early predictor of COVID‐19. Here, the effects of comorbidities on changes in taste and smell in COVID‐19 patients were investigated based on a worldwide study. Methods Data analyzed here were collected from the Global Consortium for Chemosensory Research (GCCR) core questionnaire, includin...

One of the unique symptoms of COVID-19 is chemosensory dysfunction. Almost three years since the beginning of the pandemic of COVID-19, there have been many studies on the symptoms, progress, and possible causes, and also studies on methods that may facilitate recovery of the senses. Studies have shown that some people recover their senses even wit...

The recent increase in the number of patients with post-viral olfactory dysfunction (PVOD) following the outbreak of COVID-19 has raised the general interest in and concern about olfactory dysfunction. At present, no clear method of treatment for PVOD has been established. Currently the most well-known method to improve the symptoms of olfactory dy...

Background: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was t...

p>This is a correction notice for article bjaa041 (DOI: https:// doi.org/10.1093/chemse/bjaa041), published 20 June 2020. An incorrect version of the caption to Figure 5 was mistakenly included in the published paper. An updated version is given below. Neither the data nor the paper's conclusions were affected by this correction. The authors sincer...

Importance: Sudden smell loss is a specific early symptom of COVID-19, with an estimated prevalence of ~40% to 75%. Smell impairment affects physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. Objective: To characterize smell function and recovery up to 11 months post COVI...

The year 2020 became the year of the outbreak of coronavirus, SARS-CoV-2, which escalated into a worldwide pandemic and continued into 2021. One of the unique symptoms of the SARS-CoV-2 disease, COVID-19, is the loss of chemical senses, i.e., smell and taste. Smell training is one of the methods used in facilitating recovery of the olfactory sense,...

Although the neuroscience and molecular biology of olfactory and gustatory sense have made an enormous progress during the last 30 years, there are still many venues that have not been visited yet. We also have not determined the causations of the loss of the sense of smell (anosmia) and taste (ageusia). Many people who experience dysfunction of th...

Background: The year 2020 was the year of the global COVID-19 pandemic. The severity of the situation has become so substantial that many or even most of the patients with mild to moderate symptoms had to self-isolate without specific medical treatments or even without being tested for COVID-19. Many patients joined internet membership groups to ex...

In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100...

BACKGROUND The year 2020 has now become the year of the global pandemic of coronavirus disease 2019 (COVID-19). The severity of the situation has become so extraordinary that many or even most of the patients with mild to moderate symptoms had to self-isolate without specific medical treatments or even without being tested for COVID-19. Many patien...

Background: The year 2020 has now become the year of the global pandemic of coronavirus disease 2019 (COVID-19). The severity of the situation has become so extraordinary that many or even most of the patients with mild to moderate symptoms had to self-isolate without specific medical treatments or even without being tested for COVID-19. Many pati...

Understanding how genes and experiences work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell types in mice. We identified a subpopulation of olfactory sensory neurons, defined by...

Now published in Chemical Senses doi: 10.1093/chemse/bjaa081. Background: COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19. Methods: This preregistered, cross-sectional study used a crowdsou...

Now published in Chemical Senses doi: 10.1093/chemse/bjaa041. Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, generally lacked quantitative measure...

Essential oils have been used in multiple ways, i.e., inhaling, topically applying on the skin, and drinking. Thus, there are three major routes of intake or application involved: the olfactory system, the skin, and the gastro-intestinal system. Understanding these routes is important for clarifying the mechanisms of action of essential oils. Here...

Beta-caryophyllene is an odoriferous bicyclic sesquiterpene found in various herbs and spices. Recently, it was found that beta-caryophyllene is a ligand of the cannabinoid receptor 2 (CB2). Activation of CB2 will decrease pain, a major signal for inflammatory responses. We hypothesized that beta-caryophyllene can affect wound healing by decreasing...

Understanding how genes and experiences work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the context of the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell-types, in mice. We identified a subpopulation of at least three types o...

Background: Aerobic exercise has been shown to slow tumor progression in rodents and humans, but the mechanisms behind this effect are still unclear. Here we show that aerobic exercise in the form of chronic endurance training suppresses tumor recruitment of FoxP3+ Treg cells thus enhancing antitumor immune efficiency. Methods: Adult wild-type a...

Beta-caryophyllene, an odoriferous bicyclic sesquiterpene found in various herbs and spices, is a ligand of the cannabinoid receptor 2 (CB2). Activation of the CB2 will decrease pain and we hypothesized that beta-caryophyllene can affect wound healing. Here we show that mice cutaneous wounds treated with beta-caryophyllene had enhanced re-epithelia...

Maintenance of specialized epidermis requires signals from the underlying mesenchyme; however, specific pathways involved remain to be identified. By recombining cells from ventral skin of the K14-PTHrP transgenic mice with those from wild-type, we show that transgenic stroma is sufficient to reprogram wild-type keratinocytes into nipple-like epide...

Identification of the pheromones responsible for these primer effects, which were started to be found in the 1950s, began in the 1980s. 3,4-Dehydro-exo-brevicomin (DHB), 2-sec-butyl-4,5-dihydrothiazole (SBT), E,E-α-farnesene, and E-β-farnesene present in male mouse urine were found to induce the Whitten effect. The Lee–Boot effect was found to be i...

From the end of twentieth century to the beginning of twenty-first century, several new primer effects were found, i.e., enhanced adult neurogenesis by the exposure to pheromone of opposite sex, enhanced expansion of mammary gland in females by exposure to male pheromone, enhanced sperm density by exposure to female-soiled bedding, suppressed sperm...

The 1990s became the decade that olfactory neuroscience showed extraordinary development. Now we have much better understanding of how we distinguish various odors and how the signaling pathways are in the brain. We also know that the olfactory system is not a single system but it is a group of systems in the nasal cavity that respond to chemical c...

When do we start to respond to pheromones? Olfactory sensory neurons and glomeruli in the olfactory bulbs develop mostly in postnatal stages, but studies have shown that learning and establishment of preferences to odors start from late embryonic stages. The mechanisms of olfactory learning during embryonic stages need further investigations to det...

What is the function of primer effects? Suppression of estrous cycle when males are not around (Lee–Boot effect) and coming into estrus when females are exposed to males’ odors (Whitten effect) would be highly adaptive in reproduction. Also, being unable to establish pregnancy (Bruce effect) by exposure to unfamiliar males’ odor is also adaptive co...

The discovery of primer effects in mice began in the 1950s. The findings at that time were all made with female mice. When female mice were housed in groups without the odor of males, their estrous cycles were extended (Lee–Boot effect) resulting in less frequently coming into estrus. Exposure to male odor reversed this, i.e., the females with long...

The biology of mice has been studied for centuries with the main purpose of pest control. With the advent of scientific approaches to human medical care, mice have become the most popular animal model system because of the many similarities between their physiology and that of humans. More recently, they have been used in an even broader range of s...

Springer Briefs in Animal Sciences

The keeping of pet birds in Japan is reviewed with a focus on the varied tit (Cyanistes varius). Traditionally, bird-keeping in Japan was mainly for the enjoyment of their songs. Songbird competitions were popular and training of birds to sing was common, especially in the Edo era from the seventeenth to the nineteenth centuries, which meant that i...

In mammals, some sites of specialized skin such as the palms, soles, and lips grow proportionally with the animal. However, other types of specialized skin such as the nipple and anal/genital region are dramatically altered with changes of reproductive status. The specific cell types that mediate the growth of these sites have not been identified....

Having glands that secrete milk to nourish neonatal offspring characterizes all mammals. We provide a brief overview of the development and anatomy of nipples and mammary glands in monotremes, marsupials, and marine mammals, and focus on the nipples and mammary glands in terrestrial eutherian species. We first classify eutherians into three groups:...

Whereas the house mouse (Mus domesticus) has been studied extensively in terms of physiology/behavior and pheromonal attributes, the evolutionarily related mound-building mouse (Mus spicilegus) has received attention only recently due to its divergent behavioral traits related to olfaction. To date, no chemical studies on urinary volatile compounds...

The genes of the major histocompatibility complex (MHC) are highly polymorphic loci that encode cell surface proteins, class I and II molecules. They present peptide antigens to T cells and thereby control immunological self/nonself recognition. Increasing evidence indicates that MHC genes also influence odor and mating preferences; however, it is...

Sperm chemotaxis is an area of significant interest to scientists involved in reproductive science. Understanding how and when sperm cells are attracted to the egg could have profound effects on reproduction and contraception. In an effort to systematically study this problem, we have fabricated and evaluated a microfluidic device to measure sperm...

Administration of 50 microg of bisphenol A (BPA) for the first 5 days after birth resulted in a decrease in the percentage of moving sperm, and an increase in the incidence of malformed sperm, in the epididymides of mice at 10 weeks of age, although no marked changes were found in the testicular histology between BPA-treated and vehicle-treated con...

It has been shown that sperm motility and other parameters related to the reproductive activity varied depending on the social status of male mice. In order to clarify whether such variation is derived from inborn difference or depends on any conditions during maturation, we investigated developmental change of sperm motility, reproductive organs,...

Odors play important roles in the communication of house mice. They release behaviors and prime changes of the physiological conditions of other individuals. In our previous study, we showed that sperm motility was lowered in the subordinate mice comparing with dominant mice. Our hypothesis is that the lowered sperm motility was due to some primer...

In the latter half of twentieth century, much has been learned about chemical communication in house mice (Mus musculus). It is known that urine of mice can signal information about strain, physiological state (estrus or diestrus, stressed or not), social status, and so on (Brown, 1979). Some of the volatile semiochemicals in urine have been identi...

In mammals, sperm activity is known to be varied largely according to individuals though physiological reasons have not been clarified yet. In our previous study [Koyama S, Kamimura S. Lowered sperm motility in mice of subordinate social status. Physiol Behav 1999;65:665-669.], we showed that sperm motility was higher in the dominant mice than the...

Male ddY mice were used to investigate the effect of a short period of isolation in adulthood on aggressive behavior. The relationship between the dominance status previous to isolation and the effect of isolation was investigated. The mice were kept in isolation for 3 weeks from 9 weeks of age, during which intruder tests were conducted once a wee...

Male ddY mice were used to investigate the responses toward the odor of unfamiliar male mice. They were reared either in isolation from 3 weeks of age or in pairs. At 10 weeks of age, they went through a 4-day test period, in which the responses of the mice toward the odor of unfamiliar dominant and subordinate mice were investigated by differentia...

Responses to the odor of familiar intruder male mice according to their dominance were investigated. Responses were classified into 2 aspects: the investigation of the odor and the decision-making regarding avoiding it or not. The results varied according to the dominance of the respondents and the odor donor, and also according to the context of p...

The hypothesis of dominant/territorial aggression on isolation-induced aggression was examined by comparing the behavior of isolated mice with that of familiar dominant mice. Familiar dominant mice showed as much aggression in an already known neutral space as the isolated mice. The behavioral sequences of aggression in the 2 groups showed both dif...

In previous studies, isolated mice are found to be extremely more aggressive than group-reared mice. In most of those studies, however, the pairings of the group-reared mice were randomly determined, without attention to individuals' ranks in their home cages. In this study, the effect of isolation was analyzed by comparing isolated mice with domin...