Metabolic assessment of a nonhuman primate model of metabolic syndrome and obesity requires the necessary biomarkers specific to the species. While the rhesus monkey has a number of specific assays for assessing metabolic syndrome, the marmoset does not. Furthermore, the common marmoset (Callithrix jacchus) has a small blood volume that necessitates using a single blood volume for multiple analyses. The common marmoset holds a great potential as an alternative primate model for the study of human disease but assay methods need to be developed and validated for the biomarkers of metabolic syndrome. Here we report on the adaptation, development and validation of commercially available immunoassays for common marmoset samples in small volumes. We have performed biological validations for insulin, adiponectin, leptin, and ghrelin to demonstrate the use of these biomarkers in examining metabolic syndrome and other related diseases in the common marmoset.
marmoset; Callithrix jacchus; metabolic syndrome; obesity; insulin; adiponectin; letpin; ghrelin
Most primates are social species whose reproduction is influenced by their social relationships. The cotton-top tamarin, Saguinus oedipus, and the common marmoset, Callithrix jacchus, are cooperative breeding species where the family structure alters reproductive function in many ways. While primates receive social effects on reproduction via all sensory stimuli, the marmosets and tamarins are particularly influenced by olfactory/chemosensory stimuli. The olfactory sensory processing is the ‘social glue’ that keeps the family together.
This review describes a number of studies using the marmosets and tamarins at the University of Wisconsin to demonstrate how odor cues are used for altering reproductive function and dysfunction. Several key studies will be discussed to show the role of odor signaling of the female reproductive state. The suppressive effects of odors are mediated by priming odors and can cause a suppressive influence on ovulation in young females via their mother’s scents. Additionally, odor cues from the infant function as priming odors to ensure that fathers and mothers are present and receptive to their parental care duties. Neural pathways occur via the processing of priming odors that consequently stimulate alterations in the behavioral and endocrine response to the stimuli. The dynamics of the cooperative breeding system ensure that offspring have essential needs met and that they develop in a family environment. Olfactory communication plays a key role in maintenance of the social system of Callitrichid monkeys.
Pregnancy and lactation produce a plethora of hormonal changes in females that promote maternal care of offspring. Males in the biparental marmoset species, (Callithrix jacchus), demonstrate high levels of parenting behaviour and express enhanced circulating reproductive hormones. Furthermore, these hormonal changes are influenced by paternal experience. In order to determine if the paternally experienced male marmoset has altered neurocrine hypothalamic release, as the maternal females does, we examined the release of several reproductive neurocrines, dopamine (DA), oxytocin (OT) and vasopressin (AVP) and prolactin (PRL), in cultured explants of the hypothalamus of paternally experienced male marmosets compared with naïve, paternally inexperienced males. DA levels secreted from the isolated hypothalamus were significantly lower in the experienced males while OT and PRL levels were significantly higher than levels found in inexperienced males. PRL levels decreased rapidly in the hypothalamic media suggesting PRL production occurs elsewhere. AVP levels did not change. Stimulation of the cultured explants with oestradiol significantly decreased DA levels in the inexperienced males but did not alter the other neurocrines suggesting a direct effect of oestradiol on DA suppression in the hypothalamus. While other factors such as age and rearing experience with siblings may play a role in hypothalamic neurocrine levels, these results demonstrate that paternal experience may impact the secretion of neurocrines in a male biparental primate.
paternal experience; prolactin; OT; oestradiol; dopamine; vasopressin; hypothalamus
Olfactory cues can exert priming effects on many mammalian species. Paternally experienced marmosets, Callithrix jacchus, exposed to direct isolated olfactory contact with their own infant's scent show rapid decreases in testosterone levels within 20 minutes, whereas paternally inexperienced males do not. The following study tests whether there is a differential steroid response to exposure of infant scent from dependent infants (own and novel) and independent infants (own and novel). We examined the serum levels of estradiol, estrone, testosterone, dihydrotestosterone (DHT), and combined estrogens and androgens in eight male marmosets 20 minutes after exposure to isolated infant scent. Testosterone and androgen levels combined were significantly lower with exposure to own infant scent than a novel infant scent when the infants were at a dependent age but not at an independent age. Estrogen levels elevated significantly in response to own infant scent when the infants were at a dependent age but not at an independent age. These results suggest that marmoset fathers are more responsive to priming cues from related infants and hormonal responses from fathers are greatest when the infant is at a dependent age.
olfactory communication; chemosensory; infant odors; testosterone; androgens; estrogens; marmoset; parenting
Prolactin has been implicated in promoting paternal care behaviors but little evidence of causality has been found to date except for birds and fish. This study was designed to examine the possible causal relationships between prolactin and male parenting behaviors, reproductive hormones, and physical changes in cooperatively breeding common marmosets, Callithrix jacchus. Fifteen parentally experienced fathers were studied over three consecutive infant care periods during two weeks prior and three weeks following their mates' parturition under three treatment conditions: normal control pregnancy, decreased prolactin and elevated prolactin. The treatments significantly altered the serum prolactin levels in the fathers. Using three methods of determining a father's level of parental care: infant carrying, family effort and responsiveness to infant stimulus tests, we found that only the male response to infant stimuli was altered by the hormone treatments. Lowering prolactin significantly reduced male responsiveness to infant stimuli but elevating prolactin showed the same effect. Hormonal sampling indicated that testosterone levels showed an inverse relationship to prolactin levels during a normal peripartum period and prolactin treatment reduced this relationship. Prepartum estradiol levels were significantly elevated during the lowered prolactin treatment and estradiol was significantly lowered postpartum with the elevated prolactin treatment. Father's weight decreased significantly by the third week of infant care during the normal treatment. Males in the elevated prolactin treatment lost little or no weight from prepartum while in the lowered prolactin treatment showed the most weight loss. The present findings did not distinguish a direct causal relationship of prolactin on behavior in experienced fathers but did find an interaction with other hormones and weight gain.
prolactin; paternal care; infant responsiveness; testosterone; estradiol; common marmoset; weight gain
Much attention has been paid to hormonal variation in relation to male dominance status and reproductive seasonality, but we know relatively little about how hormones vary across life history stages. Here we examine fecal testosterone (fT), dihydrotestosterone (fDHT), and glucocorticoid (fGC) profiles across male life history stages in wild white-faced capuchins (Cebus capucinus). Study subjects included 37 males residing in three habituated social groups in the Área de Conservacíon Guanacaste, Costa Rica. Male life history stages included infant (0 to <12 months; N = 3), early juvenile (1 to <3 years; N = 10), late juvenile (3 to <6 years; N = 9), subadult (6 to <10 years; N = 8), subordinate adult (≥10 years; N = 3), and alpha adult (≥ 10 years; N = 4, including one recently deposed alpha). Life history stage was a significant predictor of fT; levels were low throughout the infant and juvenile phases, doubled in subadult and subordinate adults, and were highest for alpha males. Life history stage was not a significant predictor of fDHT, fDHT:fT, or fGC levels. Puberty in white-faced capuchins appears to begin in earnest during the subadult male phase, indicated by the first significant rise in fT. Given their high fT levels and exaggerated secondary sexual characteristics, we argue that alpha adult males represent a distinctive life history stage not experienced by all male capuchins. This study is the first to physiologically validate observable male life history stages using patterns of hormone excretion in wild Neotropical primates, with evidence for a strong association between fT levels and life history stage.
Testosterone; Dihydrotestosterone (DHT); Glucocorticoids; Male development; Puberty; Dominance
Male cotton-top tamarins have been shown to be responsive to female scent cues of ovulation, and are known to actively participate in infant care during the time when their mates are fertile. We measured urinary androgen levels and glucocorticoids in seven father tamarins for the first month following the birth of infants to determine 1) whether male tamarins showed an androgen response to their mate’s postpartum ovulation, 2) when androgens rise relative to ovulation, 3) whether there is a glucocorticoid response, and 4) whether males alter their parenting behavior during their mate’s receptive period. All of the males showed a significant increase in urinary androgens prior to the female’s postpartum LH peak, which indicated ovulation. The hormonal increase, which included estradiol, occurred 3–7 days prior to the female’s LH peak at a time that coincided with the female’s follicular period. Corticosterone levels also peaked during that time, but did not correlate with androgen changes. Fathers did not alter their daily infant-carrying patterns relative to the androgen increase or at the time of the mate’s LH peak. We conclude that male cotton-top tamarins experience an increase in androgens that coincides with their mate’s postpartum ovulation, which ensures optimal fertility. However, this sexual communication does not alter father–infant interactions, which already occur at a high rate in this species.
cotton-top tamarin; androgens; glucocorticoids; chemical signaling; ovulation; parenting behavior
It is established that maternal parity can affect infant growth and risk for several disorders, but the prenatal endocrine milieu that contributes to these outcomes is still largely unknown. Recently, it has been shown that hormones deposited in hair can provide a retrospective reflection of hormone levels while the hair was growing. Taking advantage of this finding, our study utilized hair at birth to investigate if maternal parity affected fetal hormone exposure during late gestation.
Hair was collected from primiparous and multiparous mother and infant monkeys at birth and used to determine steroid hormones embedded in hair while the infant was in utero. An LC/MS/MS technique was refined, which enabled the simultaneous measurement of 8 hormones.
Hormone concentrations were dramatically higher in neonatal compared to maternal hair, reflecting extended fetal exposure as the first hair was growing. Further, hair cortisone was higher in primiparous mothers and infants when compared to the multiparous dyads.
This research demonstrates that infant hair can be used to track fetal hormone exposure and a panel of steroid hormones can be quantified from hair specimens. Given the utility in nonhuman primates, this approach can be translated to a clinical setting with human infants.
Release of gonadotropin releasing hormone (GnRH) from the medial basal hypothalamus (MBH)/median eminence region (S-ME) is essential for normal reproductive function. GnRH release is profoundly regulated by the negative and positive feedback effects of ovarian estradiol (E2). Here we report that neuroestradiol, released in the S-ME, also directly influences GnRH release in ovariectomized female monkeys, in which the ovarian source of E2 is removed. We found that (1) brief infusion of E2 benzoate (EB) to the S-ME rapidly stimulated release of GnRH and E2 in the S-ME of ovariectomized monkeys, (2) electrical stimulation of the MBH resulted in GnRH release as well as E2 release, and (3) direct infusion of an aromatase inhibitor to the S-ME suppressed spontaneous GnRH release as well as the EB-induced release of GnRH and E2. These findings reveal the importance of neuroestradiol as a neurotransmitter in regulation of GnRH release. How circulating ovarian E2 interacts with hypothalamic neuroestrogens in the control of GnRH release remains to be investigated.
We assess the common marmoset as a model of early obesity. We test the hypotheses that juvenile marmosets with excess adipose tissue will display higher fasting glucose, decreased insulin sensitivity, and decreased ability to clear glucose from the blood stream.
Design and Methods
Normal and Obese (body fat > 14%) common marmoset infants (N = 39) were followed from birth until one year. Body fat was measured by quantitative magnetic resonance. Circulating glucose was measured by glucometer; insulin, adiponenctin and leptin by commercial assays. The QUICKI (a measure of insulin sensitivity) was calculated for subjects with fasting glucose and insulin measures. Oral glucose tolerance tests were conducted at 12 months on 35 subjects.
At 6 months Obese subjects already had significantly lower insulin sensitivity (mean QUICKI = .378±.029 versus .525±.019, N=11, p=.003). By 12 months Obese subjects also had higher fasting glucose (129.3±9.1 mg/dL versus 106.1±6.5 mg/dL, p=.042) and circulating adiponectin tended to be lower (p=.057). Leptin was associated with percent body fat; however, birth weight also influenced circulating leptin. The OGTT results demonstrated that Obese animals had a decreased ability to clear glucose.
Early onset obesity in marmosets results in impaired glucose homeostasis by one year.
insulin sensitivity; glucose; leptin; adiponectin
The neuropeptide, oxytocin, receives increasing attention due to its role in stress regulation and promoting affiliative social behavior. Research across mammals points to a complex pattern whereby social context and individual differences moderate the central release of oxytocin as well as moderate the effects that exogenous administration of oxytocin has on social behavior. In addition, it is becoming evident that measuring endogenous peripheral oxytocin levels is an informative tool. This is particularly so when oxytocin can be measured from non-invasively collected samples, such as in urine. Although it is still debated as to whether peripheral measures of oxytocin relate to central measures of oxytocin, anatomical and functional evidence indicate a link between the two. We argue that non-invasive measures of peripheral oxytocin hold several research and potential therapeutic advantages. Principally, study subjects can be sampled repeatedly in different social contexts where social history between interaction partners can be taken into account. Several hormones can be measured simultaneously allowing examination of the influence of oxytocin interactions with other hormones on motivational states. Valence of relationships as well as changes in relationship quality over time can be measured through endocrine responses. Also, the approach of identifying natural social contexts that are associated with endogenous oxytocin release offers the potential of behavioral therapy as an addition or alternative to chemical therapy in the field of mental health.
endogenous peripheral oxytocin; non-invasive sampling; multi-hormone sampling; social bonds; social interaction dynamics; cooperation
Numerous studies have examined the effects of anthropogenic endocrine disrupting compounds; however, very little is known about the effects of naturally occurring plant-produced estrogenic compounds (i.e., phytoestrogens) on vertebrates. To examine the seasonal pattern of phytoestrogen consumption and its relationship to hormone levels (407 fecal samples analyzed for estradiol and cortisol) and social behavior (aggression, mating, and grooming) in a primate, we conducted an 11-month field study of red colobus (Procolobus rufomitratus) in Kibale National Park, Uganda. The percent of diet from estrogenic plants averaged 10.7% (n = 45 weeks; range: 0.7 – 32.4%). Red colobus fed more heavily on estrogenic Millettia dura young leaves during weeks of higher rainfall, and the consumption of this estrogenic item was positively correlated to both their fecal estradiol and cortisol levels. Social behaviors were related to estradiol and cortisol levels, as well as the consumption of estrogenic plants and rainfall. The more the red colobus consumed estrogenic plants the higher their rates of aggression and copulation and the lower their time spent grooming. Our results suggest that the consumption of estrogenic plants has important implications for primate health and fitness through interactions with the endocrine system and changes in hormone levels and social behaviors.
estradiol; cortisol; environmental endocrinology; herbivory; mating; phytoestrogen; aggression; Kibale National Park; grooming; legume
The neuro-hypophysial hormone oxytocin (OT) has been implicated in female reproductive and maternal behavior and in the formation of pair bonds in monogamous species. Here we measure variation in urinary OT concentrations in relation to reproductive biology and socio-sexual behavior in a promiscuously breeding species, the chacma baboon (Papio hamadryas ursinus). Subjects were members of a habituated group of baboons in the Okavango Delta, Botswana. We collected behavioral data and urine samples from n= 13 cycling females across their estrous cycles and during and outside of short-term, exclusive sexual consortships. Samples were analyzed via Enzyme Immunoassay (EIA) and we used linear mixed models (LMM) to explore the relationship between peripheral OT and a female’s estrous stage and consortship status, her previous reproductive experience and fertility. We also used a Pearson’s correlation to examine the relationship between OT concentrations of consorting females and their extent of behavioral coordination with their consort partners. The results of the LMM indicate that only estrous stage had a significant influence on OT levels. Females had higher OT levels during their periovulatory period than during other stages of their estrous cycle. There were no differences in OT levels between consorting and non-consorting periovulatory females. However, among consorting females, there was a significant positive relationship between urinary OT levels and the maintenance of close proximity between consort partners. Our results suggest that physiological and behavioral changes associated with the initiation and maintenance of short-term inter-sexual relationships in baboons correspond with changes in peripheral OT.
Consortship; estrous cycle; oxytocin; chacma baboons; Papio hamadryas ursinus; socio-sexual behavior; non-invasive hormone sampling
The common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate aging model. With an average lifespan of 5 to 7 years and a maximum lifespan of 16.5 years, marmosets are the shortest-lived anthropoid primates. They display age-related changes in pathologies that mirror those seen in humans, such as cancer, amyloidosis, diabetes, and chronic renal disease. They also display predictable age-related differences in lean mass, calf circumference, circulating albumin, hemoglobin, and hematocrit. Features of spontaneous sensory and neurodegenerative change—for example, reduced neurogenesis, β-amyloid deposition in the cerebral cortex, loss of calbindin D28k binding, and evidence of presbycusis—appear between the ages of 7 and 10 years. Variation among colonies in the age at which neurodegenerative change occurs suggests the interesting possibility that marmosets could be specifically managed to produce earlier versus later occurrence of degenerative conditions associated with differing rates of damage accumulation. In addition to the established value of the marmoset as a model of age-related neurodegenerative change, this primate can serve as a model of the integrated effects of aging and obesity on metabolic dysfunction, as it displays evidence of such dysfunction associated with high body weight as early as 6 to 8 years of age.
aging research; hearing loss; marmoset (Callithrix jacchus); neurodegeneration; nonhuman primate (NHP); obesity
Conditioning of sexual arousal has been demonstrated in several species from fish to humans, but has not been demonstrated in nonhuman primates. Controversy exists over whether nonhuman primates produce pheromones that arouse sexual behavior. Although common marmosets copulate throughout the ovarian cycle and during pregnancy, males exhibit behavioral signs of arousal, demonstrate increased neural activation of anterior hypothalamus and medial preoptic area and have an increase in serum testosterone after exposure to odors of novel ovulating females suggestive of a sexually arousing pheromone. Males also have increased androgens prior to their mate’s ovulation. However, males presented with odors of ovulating females demonstrate activation of many other brain areas associated with motivation, memory and decision making. In this study we demonstrate that male marmosets can be conditioned to a novel, arbitrary odor (lemon) with observation of erections, and increased exploration of the location where they previously experienced a receptive female, and increased scratching in postconditioning test without a female present. This conditioned response was demonstrated up to a week after the end of conditioning trials, a much longer lasting effect of conditioning than reported in studies of other species. These results further suggest that odors of ovulating females are not pheromones, strictly speaking, and that marmoset males may learn specific characteristics of odors of females providing a possible basis for mate identification.
Sexual conditioning; sexual arousal; pheromones; common marmosets; pair-bonding
Human speech evidently conveys an adaptive advantage, given its apparently rapid dissemination through the ancient world and global use today. As such, speech must be capable of altering human biology in a positive way, possibly through those neuroendocrine mechanisms responsible for strengthening the social bonds between individuals. Indeed, speech between trusted individuals is capable of reducing levels of salivary cortisol, often considered a biomarker of stress, and increasing levels of urinary oxytocin, a hormone involved in the formation and maintenance of positive relationships. It is not clear, however, whether it is the uniquely human grammar, syntax, content and/or choice of words that causes these physiological changes, or whether the prosodic elements of speech, which are present in the vocal cues of many other species, are responsible. In order to tease apart these elements of human communication, we examined the hormonal responses of female children who instant messaged their mothers after undergoing a stressor. We discovered that unlike children interacting with their mothers in person or over the phone, girls who instant messaged did not release oxytocin; instead, these participants showed levels of salivary cortisol as high as control subjects who did not interact with their parents at all. We conclude that the comforting sound of a familiar voice is responsible for the hormonal differences observed and, hence, that similar differences may be seen in other species using vocal cues to communicate.
Middle childhood; Females; Oxytocin; Instant messaging; Vocal communication; Social behavior; Human evolution
Proton pump inhibitors (PPIs) increase osteoporotic fracture risk presumably via hypochlorhydria and consequent reduced fractional calcium absorption (FCA). Existing studies provide conflicting information regarding the direct effects of PPIs on FCA. We evaluated the effect of PPI therapy on FCA. We recruited women at least 5 years past menopause who were not taking acid suppressants. Participants underwent three 24-hour inpatient FCA studies using the dual stable isotope method. Two FCA studies were performed 1 month apart to establish baseline calcium absorption. The third study occurred after taking omeprazole (40 mg/day) for 30 days. Each participant consumed the same foods during all FCA studies; study meals replicated subjects' dietary habits based on 7-day diet diaries. Twenty-one postmenopausal women ages 58 ± 7 years (mean ± SD) completed all study visits. Seventeen women were white, and 2 each were black and Hispanic. FCA (mean ± SD) was 20% ± 10% at visit 1, 18% ± 10% at visit 2, and 23% ± 10% following 30 ± 3 days of daily omeprazole (p = .07, ANOVA). Multiple linear regression revealed that age, gastric pH, serum omeprazole levels, adherence to omeprazole, and 25-hydroxyvitamin D levels were unrelated to changes in FCA between study visits 2 and 3. The 1,25-dihydroxyvitamin D3 level at visit 2 was the only variable (p = .049) associated with the change in FCA between visits 2 and 3. PPI-associated hypochlorhydria does not decrease FCA following 30 days of continuous use. Future studies should focus on identifying mechanisms by which PPIs increase the risk of osteoporotic fracture. © 2010 American Society for Bone and Mineral Research.
ACID SUPPRESSANT; BONE; CALCIUM ABSORPTION; FRACTURE; OSTEOPOROSIS
Vocalizations are important components of social behaviour in many vertebrate species, including our own. Less well-understood are the hormonal mechanisms involved in response to vocal cues, and how these systems may influence the course of behavioural evolution. The neurohormone oxytocin (OT) partly governs a number of biological and social processes critical to fitness, such as attachment between mothers and their young, and suppression of the stress response after contact with trusted conspecfics. Rodent studies suggest that OT's release is contingent upon direct tactile contact with such individuals, but we hypothesized that vocalizations might be capable of producing the same effect. To test our hypothesis, we chose human mother–daughter dyads and applied a social stressor to the children, following which we randomly assigned participants into complete contact, speech-only or no-contact conditions. Children receiving a full complement of comfort including physical, vocal and non-verbal contact showed the highest levels of OT and the swiftest return to baseline of a biological marker of stress (salivary cortisol), but a strikingly similar hormonal profile emerged in children comforted solely by their mother's voice. Our results suggest that vocalizations may be as important as touch to the neuroendocrine regulation of social bonding in our species.
oxytocin; stress; vocalizations; female; children; social bonding
Oxytocin plays an important role in monogamous pairbonded female voles, but not in polygamous voles. Here we examined a socially-monogamous cooperatively breeding primate where both sexes share in parental care and territory defense for within species variation in behavior and female and male oxytocin levels in 14 pairs of cotton-top tamarins (Saguinus oedipus), In order to obtain a stable chronic assessment of hormones and behavior, we observed behavior and collected urinary hormonal samples across the tamarins’ three week ovulatory cycle. We found similar levels of urinary oxytocin in both sexes. However, basal urinary oxytocin levels varied ten-fold across pairs and pair-mates displayed similar oxytocin levels. Affiliative behavior (contact, grooming, sex) also varied greatly across the sample and explained more than half the variance in pair oxytocin levels. The variables accounting for variation in oxytocin levels differed by sex. Mutual contact and grooming explained most of the variance in female oxytocin levels whereas sexual behavior explained most of the variance in male oxytocin levels. The initiation of contact by males and solicitation of sex by females were related to increased levels of oxytocin in both. This study demonstrates within-species variation in oxytocin that is directly related to levels of affiliative and sexual behavior. However, different behavioral mechanisms influence oxytocin levels in males and females and a strong pair relationship (as indexed by high levels of oxytocin) may require the activation of appropriate mechanisms for both sexes.
Oxytocin; affiliative behavior; cotton-top tamarins; monogamy; cooperative breeding; sex differences
Activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ) has been proposed as a possible neuroprotective strategy to slow down the progression of early Parkinson's disease (PD). Here we report preclinical data on the use of the PPAR-γ agonist pioglitazone (Actos®; Takeda Pharmaceuticals Ltd.) in a paradigm resembling early PD in nonhuman primates.
Rhesus monkeys that were trained to perform a battery of behavioral tests received a single intracarotid arterial injection of 20 ml of saline containing 3 mg of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Twenty-four hours later the monkeys were assessed using a clinical rating scale, matched accordingly to disability, randomly assigned to one of three groups [placebo (n = 5), 2.5 (n = 6) or 5 (n = 5) mg/kg of pioglitazone] and their treatments started. Three months after daily oral dosing, the animals were necropsied.
We observed significant improvements in clinical rating score (P = 0.02) in the animals treated with 5 mg/kg compared to placebo. Behavioral recovery was associated with preservation of nigrostriatal dopaminergic markers, observed as higher tyrosine hydroxylase (TH) putaminal optical density (P = 0.011), higher stereological cell counts of TH-ir (P = 0.02) and vesicular monoamine transporter-2 (VMAT-2)-ir nigral neurons (P = 0.006). Stereological cell counts of Nissl stained nigral neurons confirmed neuroprotection (P = 0.017). Pioglitazone-treated monkeys also showed a dose-dependent modulation of CD68-ir inflammatory cells, that was significantly decreased for 5 mg/kg treated animals compared to placebo (P = 0.018). A separate experiment to assess CSF penetration of pioglitazone revealed that 5 mg/kg p.o. induced consistently higher levels than 2.5 mg/kg and 7.5 mg/kg. p.o.
Our results indicate that oral administration of pioglitazone is neuroprotective when administered early after inducing a parkinsonian syndrome in rhesus monkeys and supports the concept that PPAR-γ is a viable target against neurodegeneration.
To evaluate brain activity associated with sexual arousal, fully conscious male marmoset monkeys were imaged during presentation of odors that naturally elicit high levels of sexual activity and sexual motivation.
Material and Methods
Male monkeys were lightly anesthetized, secured in a head and body restrainer with a built-in birdcage resonator and positioned in a 9.4-Tesla spectrometer. When fully conscious, monkeys were presented with the odors of a novel receptive female or an ovariectomized monkey. Both odors were presented during an imaging trial and the presentation of odors was counterbalanced. Significant changes in both positive and negative BOLD signal were mapped and averaged.
Periovulatory odors significantly increased positive BOLD signal in several cortical areas: the striatum, hippocampus, septum, periaqueductal gray, and cerebellum, in comparison with odors from ovariectomized monkeys. Conversely, negative BOLD signal was significantly increased in the temporal cortex, cingulate cortex, putamen, hippocampus, substantia nigra, medial preoptic area, and cerebellum with presentation of odors from ovariectomized marmosets as compared to periovulatory odors. A common neural circuit comprising the temporal and cingulate cortices, putamen, hippocampus, medial preoptic area, and cerebellum shared both the positive BOLD response to periovulatory odors and the negative BOLD response to odors of ovariectomized females.
These data suggest the odor-driven enhancement and suppression of sexual arousal affect neuronal activity in many of the same general brain areas. These areas included not only those associated with sexual activity, but also areas involved in emotional processing and reward.
BOLD technique; approach/avoidance; magnetic resonance imaging; functional imaging; common marmoset; cerebellum; neural circuit; sexual motivation; suppressed sexual activity
In cooperatively breeding groups of mammals, reproduction is usually restricted to a small number of individuals within the social group. Sexual development of mammals can be affected by social environment, but we know little regarding effects of the cooperative-breeding system on males. Cotton-top tamarin (Saguinus oedipus oedipus) offspring typically do not reproduce in their natal group, even though they may be physically mature. We examined neonatal and pubertal development in captive male cotton-top tamarins as an example of reproductive development within a cooperative-breeding system and to compare cotton-top tamarins with the general primate model. Puberty was characterized using both hormonal and physical measures. Data were collected on urinary levels of LH, testosterone (T), dihydrotestosterone (DHT), cortisol, and the ratio of DHT to T; testicular development; body weight; and breeding age. We determined that 1) pubertal LH secretion began at Week 37, 2) a surge of T secretion followed at Weeks 41–44, and 3) an increase in the metabolism of T to DHT may have occurred at an average age of 48.6 wk. Most of the rapid weight gain was completed by Week 24, before hormonal increases and rapid scrotal growth. We concluded that rapid pubertal testicular growth in captive cotton-top males was completed by an average 76 wk, but that completion of the individual pubertal spurt can occur between 56 and 122 wk. In a cooperative-breeding system, the opportunity for successful reproduction is dictated by the social environment, but we found no evidence that male offspring were developmentally suppressed in their natal social groups. Our findings suggest that puberty in male New World callitrichid primates occurs more quickly than puberty in Old World primates, even though both have similar patterns of development.
developmental biology; luteinizing hormone; puberty; steroid hormones; testis
Paternal behaviour is critical for the survival of offspring in many monogamous species. Common marmoset (Callithrix jacchus) and cotton-top tamarin (Saguinus oedipus) fathers spend as much or more time caring for infants than mothers. Expectant males of both species showed significant increases in weight across the pregnancy whereas control males did not (five consecutive months for marmoset males and six months for cotton-top tamarin males). Expectant fathers might be preparing for the energetic cost of fatherhood by gaining weight during their mate’s pregnancy.
weight gain; paternal care; couvades; primates
We describe the role of social odours in sexual arousal and maintaining pairbonds in biparental and cooperatively breeding primates. Social odours are complex chemical mixtures produced by an organism that can simultaneously provide information about species, kinship, sex, individuality and reproductive state. They are long lasting and have advantages over other modalities. Both sexes are sensitive to changes in odours over the reproductive cycle and experimental disruption of signals can lead to altered sexual behaviour within a pair. We demonstrate, using functional magnetic resonance imaging (fMRI), that social odours indicating reproductive state directly influence the brain areas responsible for sexual behaviour. Social odours also influence other brain areas typically involved in motivation, memory and decision making, suggesting that these signals have more complex functions in primates than mere sexual arousal. We demonstrate a rapid link between social odours and neuroendocrine responses that are modulated by a male's social status. Recent work on humans shows similar responses to social odours. We conclude with an integration of the importance of social odours on sexual arousal and maintaining pairbonds in socially biparental and cooperatively breeding species, suggesting new research directions to integrate social behaviour, neural activation and neuroendocrine responses.
social odours; sexual arousal; pairbonds; primates; functional magnetic resonance imaging; neuroendocrine responses
Paternal behaviour is critical for the survival of offspring in many monogamous species. Common marmoset (Callithrix jacchus) and cotton-top tamarin (Saguinus oedipus) fathers spend as much or more time caring for infants than mothers. Expectant males of both species showed significant increases in weight across the pregnancy whereas control males did not (five consecutive months for marmoset males and six months for cotton-top tamarin males). Expectant fathers might be preparing for the energetic cost of fatherhood by gaining weight during their mate's pregnancy.
weight gain; paternal care; couvade; primates