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Fabienne Aujard

Publications and source records attributed to Fabienne Aujard.

14 recordsLinked to original sources

Behavioral thermoregulation in a non human primate: effects of age and photoperiod on temperature selection.

Deficits in autonomic thermoregulatory capacities have been identified in aged humans and animals, but little is known about the effect of aging on behavioral thermoregulation and the potential effect of season. Preferred ambient temperature (T(a)) in a thermal gradient (available T(a)s from 10 to 30 degrees C) was measured in the mouse lemur, a nocturnal Malagasy primate. Male mouse lemurs (40 adults and 40 aged) were studied under short (SP, resting season) and long photoperiod (LP, breeding season). Additionally, daily body temperature rhythm was telemetrically recorded in 30 individuals of both age categories. In adults exposed to SP, a choice for warm climates was observed, with a mean diurnal T(a) of 26 degrees C. Day-night differences in selected T(a) occurred only in animals exposed to SP. In LP, selection of a warm environment did not seem to be a necessary factor for maintenance of normothermia. Aged animals selected warmer T(a)s than adults during the night like during the day, whatever the photoperiod. In relation to changes in body temperature rhythm according to age, aged animals would select warmer environments possibly to compensate autonomic deficiencies. Further studies on age-related changes in hormonal and cellular functions involved in energy balance and thermoregulation will help decipher the causes of insufficient responses to thermal stress observed in the elderly.

Aging↗

[Aging and biological rhythms in primates].

All living organisms exhibit rhythmic activities in a wide variety of endocrine and behavioural parameters. These biological rhythms are endogenously generated by a circadian clock, and they are entrained by cyclic variations of environmental factors called synchronizers. Aging is associated with changes in amplitude and temporal organization of many daily and seasonal rhythms. In humans, daily rhythms of sleep, thermoregulation and hormonal secretion are severely altered with aging. Except in humans, studies on primates are scarce. However, age-related effects on biological rhythms are relatively consistent among primate species studied to date, including humans. Therefore, non human primates are of valuable use for such investigations. Most studies have been performed on the Rhesus macaque (longevity 35-40 years) and on the gray mouse lemur (longevity 10-12 years). Like in humans, the rest-activity rhythm becomes fragmented in aged primates, and shows an increased activity during the resting period. Aging induces a decrease in amplitude of the body temperature rhythm and an increase in energy consumption. Various hormonal secretions exhibit a decrease with aging, but the rhythmic components of these declines have not always been depicted. Moreover, changes (amplitude or phase) in daily variations depended of the hormonal secretion tested. Taken together, these results suggest that the biological clock in the brain would be a primary target of aging. The main central clock is located in the suprachiasmatic nucleus of the hypothalamus whose endogenous oscillations are entrained by light. In this brain structure, cellular function and sensitivity to light show drastic changes with age in the mouse lemur. The precise knowledge of age-related alterations of biological rhythms in primates can have important consequences on the development of new treatments to maintain or restore biological rhythmicity in the elderly.

Aging↗

Age-related effects on the biological clock and its behavioral output in a primate.

In humans, activity rhythms become fragmented and attenuated in the elderly. This suggests an alteration of the circadian system per se that could in turn affect the expression of biological rhythms. In primates, very few studies have analyzed the effect of aging on the circadian system. The mouse lemur provides a unique model of aging in non-human primates. To assess the effect of aging on the circadian system of this primate, we recorded the circadian and daily rhythms of locomotor activity of mouse lemurs of various ages. We also examined age-related changes in the daily rhythm of immunoreactivities for vasoactive intestinal polypeptide (VIP) and arginine-vasopressin (AVP) in suprachiasmatic nucleus neurons (SCN), two major peptides of the biological clock. Compared to adult animals, aged mouse lemurs showed a significant increase in daytime activity and an advanced activity onset. Moreover, when maintained in constant dim red light, aged animals exhibited a shortening of the free-running period compared to adult animals. In adults, AVP immunoreactivity (ir) peaked during the second part of the day, and VIP ir peaked during the night. In aged mouse lemurs, the peaks of AVP ir and VIP ir were significantly shifted with no change in amplitude. AVP ir was most intense at the beginning of the night; whereas, VIP ir peaked at the beginning of the daytime. A weakened oscillator could account for the rhythmic disorders often observed in the elderly. Changes in the daily rhythms of AVP ir and VIP ir may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby modify the expression of some biological rhythms.

Aging↗

Age effects on pheromone induced Fos expression in olfactory bulbs of a primate.

In the gray mouse lemur, a prosimian primate, aging is associated with a reduction of olfactory behaviors and sexual stimulation. To assess the effect of aging on the central response to pheromone stimulation in this primate, we measured the c-fos expression in the main and accessory olfactory bulbs of adult and aged male mouse lemurs, following exposure to the volatile phase of urine from proestrous females. In adults, pheromone exposure increased the number of Fos-positive neurons in the main olfactory bulb without changes in the accessory olfactory bulb. Fos expression was not increased by the odorant stimulation in aged mouse lemurs. Our results may explain the age-related decrease in behaviors associated with olfactory stimulation in this primate.

Aging↗

Gonadotropin-releasing hormone (GnRH) immunoreactive neurons in male mouse lemurs following removal of the vomeronasal organ.

Removal of the vomeronasal organ (VNO) in male mouse lemurs led to an increase in the number of immunoreactive gonadotropin-releasing hormone (GnRH) neurons in the medial preoptic area, compared to control males. No difference was found in the mediobasal hypothalamus. In this primate, which presents a fully functional VNO, the anterior part of the hypothalamus could be the major target for VNO-mediated regulation of GnRH function and the subsequent modulation of chemosensory dependent reproductive behavior.

Animals↗

Aging and season affect plasma dehydroepiandrosterone sulfate (DHEA-S) levels in a primate.

In humans, plasma concentration of dehydroepiandrosterone sulfate (DHEA-S) declines with age and is considered as a potential predictor of longevity. DHEA-S is apparently unique to primates but few species of nonhuman primates have been studied for age-related changes in DHEA-S. In a short living primate, the grey mouse lemur (longevity 10-13 years), metabolic and physiological parameters exhibit high seasonal changes with age-related decrease in amplitude. From 8 month- to 11-year-old males (N = 175), plasma DHEA-S levels were measured either during the breeding season or during the winter sexual rest. Plasma DHEA-S levels show high significant changes according to season and age. During winter, DHEA-S levels were maintained low and constant over lifetime. During the summer breeding season, a decline of DHEA-S levels occurred after the age of 3 years and accelerated after the age of 6 years. DHEA-S level was about 30-40% of its adult value with age over 6 years, a stepwise pattern most closely resembling to human pattern. In mouse lemur, DHEA-S met the criteria for a biomarker of aging. When correlated to other age-related changes, the results give the opportunity to consider the mouse lemur as a promising primate model to study aging processes.

Aging↗

Arginine-vasopressin and vasointestinal polypeptide rhythms in the suprachiasmatic nucleus of the mouse lemur reveal aging-related alterations of circadian pacemaker neurons in a non-human primate.

The suprachiasmatic nucleus (SCN) of the hypothalamus, the mammalian circadian pacemaker, is entrained by external cues and especially by photic information. Light is transmitted primarily via the retinohypothalamic tract, which terminates in the ventral part (or core) of the SCN, where vasoactive intestinal polypeptide (VIP)-containing neurons are located. VIP cells are mainly intrinsic and project to the dorsal part (or shell) of the SCN, where neurons containing arginine-vasopressin (AVP) reside. As aging leads to marked changes in the expression of circadian rhythms, we examined in primates whether age-related decay in biological rhythmicity is associated with changes in the oscillation of peptide expression in SCN neurons. We used double immunohistochemistry and quantitative analysis in the SCN of mouse lemurs, which provide a unique model of aging in non-human primates. In adult animals, VIP-positive and AVP-positive SCN neurons exhibited daily rhythms of their number and immunostaining intensity: AVP immunoreactivity peaked during the second part of the day, and VIP peaked during the night. In aged mouse lemurs, the peaks of AVP and VIP immunopositivity were significantly shifted, so that AVP was most intense at the beginning of the night, whereas VIP peaked at the beginning of daytime. The results show that the circadian rhythm of neuropeptides in the SCN is modified by aging in primates, with a differential regulation of the two main peptidergic cell populations. These changes may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby to modify the expression of some biological rhythms.

Aging↗

Are age-related deficits in balance performance mediated by time of day in a prosimian primate (Microcebus murinus)?

We examined the effects of age and time of day on balance performance in the gray mouse lemur (Microcebus murinus) in relation to body temperature variations. Groups of young, adult and aged animals were entrained to either short (SP, L/D 10/14) or long photoperiod (LP, L/D 14/10) and tested in the accelerating Rotarod at three phases of their light/dark cycle (beginning and end of the light phase, beginning of the dark phase). In addition, for each test, rectal temperature (Tr) was measured. Under LP, whatever the test phase, this primate showed a clear age-related decrease in balance performance. Under SP, no significant age-related decline in balance could be detected. Whatever the photoperiod, an effect of time of day on balance performance could only be seen in adults, with better performances at the beginning of the dark phase when Tr values were higher. Under LP, daily variations of both balance performance and Tr disappeared with advancing age. Consequently, age differences were substantially greater when testing was conducted during the dark phase of the light/dark cycle. The time of day effect on balance performance and the loss of daily variations with age suggest the influence of age-related changes within the biological clock.

Age Factors↗

Response to urinary volatiles and chemosensory function decline with age in a prosimian primate.

The age-related decline in olfaction is well documented in humans. However, no data are available to date on changes in olfactory sensitivity with age in nonhuman primates. In the male gray mouse lemur (Microcebus murinus), a prosimian primate, the sense of smell is of high relevance for the modulation of both behavioral and physiological functions. We first assessed the effect of aging on physiological responses to urinary cues by measuring reproductive function in adult and aged males exposed to urine odor of preoestrous females. We then evaluated the effect of aging on chemosensory function using a discrimination test in freely behaving animals. Our results indicate that whereas adult animals show a clear increase in testosterone levels when exposed to female urine odor, this effect is lacking in aged animals. In addition, chemosensory function shows a progressive decline with age. Using both physiological responses to urinary volatiles and spontaneous behavior, this study provides the first data set on the effect of aging on chemosensory responsiveness in a nonhuman primate.

Aging↗

Regional atrophy in the brain of lissencephalic mouse lemur primates: measurement by automatic histogram-based segmentation of MR images.

Age-related regional cerebral atrophy was evaluated in a small lissencephalic primate, model of cerebral aging. Twelve mouse lemurs (Microcebus murinus), ages 1.9-10.9 years (maximum life span: 12 years), were studied. 3D inversion-recovery fast spin-echo MR images (isotropic resolution = 234 mum) were recorded at 4.7 T with a surface coil actively decoupled from the transmitting birdcage probe. The surface coil-related sensitivity gradient was corrected by normalization with images from an agar and NaCl phantom. An automatic statistical segmentation technique based on a classification-maximization algorithm was tested on digital phantoms that mimicked the brain and applied to the 3D brain images. Segmented 3D maps that displayed gray matter, white matter, and cerebro-spinal fluid (CSF) voxels were computed. The ventricles and peri-encephalic spaces were categorized into 14 regions, defined on brain atlases on the basis of cytoarchitectural and anatomical criteria. The volume of CSF voxels belonging to each of these regions was calculated as an index of regional atrophy. Dilation of the mammillary fossa was an early event in the aging process. CSF accumulation within the occipital, parieto-temporal, temporal, and frontal ventral peri-encephalic spaces was particularly marked in the oldest animals that also displayed ophthalmologic alterations.

Aging↗

Physical activity and balance performance as a function of age in a prosimian primate (Microcebus murinus).

Physical activity and balance performance were examined in gray mouse lemurs (Microcebus murinus) aging from 1 to 10 years of age. Home cage spontaneous activity, physical and behavioral activities in an open-field test and balance performance at the Rotarod test were evaluated. In this prosimian primate, which life span reaches 8-10 years in captivity, balance performance at the Rotarod test showed a clear decrease with age. Latency to fall decreased from 154.7+/-13.5s in the youngest group of animals to 31.2+/-5.4s in animals aging 6 years or more. A significant decrease was noticeable as early as 4 years of age. In a familiar cage, locomotor activity and jumping frequency were reduced in aged animals compared to adults. In contrast, when introduced in an open field, aged animals exhibited an increase in locomotor activity and sniffing frequency when compared to younger animals, while latency to first movement was higher in the adult than in the aged subjects. Based on these results, repeated behavioral testing should be initiated early in the life of this species, in association with an evaluation of visual and olfactory capacities. These findings are important to take into account if detailed evaluations of sensory-motor performances are required in studies on aging processes in primates.

Aging↗

Olfactory bulbectomy modifies photic entrainment and circadian rhythms of body temperature and locomotor activity in a nocturnal primate.

Studies on rodents have emphasized that removal of the olfactory bulbs modulates circadian rhythmicity. Using telemetric recordings of both body temperature (Tb) and locomotor activity (LA) in a male nocturnal primate, the gray mouse lemur, the authors investigated the effects of olfactory bulbectomy on (1) the circadian periods of Tb and LA in constant dim light condition, and (2) photic re-entrainment rates of circadian rhythms following 6-h phase shifts of entrained light-dark cycle (LD 12:12). Under free-running condition, bulbectomized males had significantly shorter circadian periods of Tb and LA rhythms than those of control males. However, the profiles of Tb rhythms, characterized by a phase of hypothermia at the beginning of the subjective day, and Tb parameters were not modified by olfactory bulbectomy. Under a light-dark cycle, olfactory bulbectomy significantly modified the expression of daily hypothermia, especially by an increase in the latency to reach minimal daily Tb, suggesting a delayed response to induction of daily hypothermia by light onset. Reentrainment rates following both a 6-h phase advance and a 6-h phase delay of entrained LD were also delayed in bulbectomized males. Olfactory bulbectomy led to significant fragmentation of locomotor activity and increased locomotor activity levels during the resting period. The shortening of circadian periods in bulbectomized males could partly explain the delayed responses to photic stimuli since in control males, the longer the circadian period, the better the response to light entrainment. This experiment shows for the 1st time that olfactory bulbs can markedly modify the circadian system in a primate.

Animals↗

Ocular findings in two colonies of gray mouse lemurs (Microcebus murinus).

OBJECTIVE: To determine the incidence and describe the characteristics of cataracts and other ocular lesions found in two colonies of gray mouse lemurs (Microcebus murinus). ANIMALS STUDIED: A total number of 218 mouse lemurs (age range: 4 months-11 years) were included in this study. All individuals were property of the Muséum National d'Histoire Naturelle (France), and were housed either in Paris (colony #1: 75 animals examined), or in Brunoy (colony #2: 143 animals). METHODS: Ocular examinations were performed on all animals before and after pupil dilation, and included slit-lamp biomicroscopy and indirect ophthalmoscopy. In both colonies, a limited number of individuals were re-examined between several months and 2 years following the initial eye examinations. The eyes of five mouse lemurs with incipient or immature cataracts that died during this period were collected, and processed for routine histopathologic examination. RESULTS: A high incidence of cataracts was observed in both colonies (48% in colony #1; 21% in colony #2). Cataracts were predominantly bilateral, started in the anterior and/or posterior subcapsular area, and appeared to be slowly progressive. The earliest age at which lens opacities were observed was 3.5 years, and more than 50% of mouse lemurs over 7 years of age were diagnosed with cataracts. Complete cataracts led to blindness and were occasionally associated with other ocular lesions. CONCLUSION: We report a high incidence of acquired, slowly progressive, bilateral cataracts in two colonies of mouse lemurs (Microcebus murinus). Further studies need to be conducted to determine the cause of this disease in this species.

Animals↗