Biomedical subjects

P Poindron

Publications and source records attributed to P Poindron.

At least 19 recordsLinked to original sources

PubMed2006

Stimulation of estrous behavior in grazing female goats by continuous or discontinuous exposure to males.

Two experiments were conducted during the anestrous period to determine: (1) whether males rendered sexually active by exposure to artificial long days stimulate estrous activity of female goats under grazed conditions (Exp. 1); and (2) whether continuous presence of the buck is necessary to stimulate this estrous activity (Exp. 2). In Exp. 1, 2 groups of females (n = 20/group), one in confinement and another under grazing conditions, were exposed to 4 bucks subjected to natural photoperiod (2 males/group). Two other groups of females (n = 20/group), in confinement or grazing, were exposed to 4 males treated with artificial long days (2 males/group). All groups were exposed to males for 15 d. The percentage of does detected in estrus during these 15 d was greater (P < 0.001) in the 2 groups exposed to males sexually prepared by long days (confined, 95%; grazed, 90%) than in groups exposed to males in natural photoperiod (confined, 15%; grazed, 45%). Does in Exp. 2 were allowed to graze and were exposed continuously (n = 26) or discontinuously (from 1700 to 0900; n = 26) for 18 d to males that had been stimulated to enter the breeding season by exposure to long days. The proportion of does that displayed estrous behavior in 18 d did not differ (P = 0.55) between groups (96.2 and 92.3% for continuous and discontinuous groups, respectively). The results indicate that anestrous goats managed under grazing conditions can be stimulated to express estrus by joining with males previously exposed to artificial long days. Continuous presence of the male is not necessary for this male effect.

Animal Husbandry↗

PubMed2006

Cyclin dependent kinase inhibitors prevent apoptosis of postmitotic mouse motoneurons.

Recent evidence suggests that apoptosis in post-mitotic neurons involves an aborted attempt of cells to re-enter the cell cycle which is characterized by increased expression of cyclins, such as cyclin D1, prior to death. However, such cyclins activation prior to apoptotic cell death remains controversial. Many neurological disorders are characterized by neuronal loss, particularly amyotrophic lateral sclerosis (ALS). ALS is a motoneuronal degenerative condition in which motoneuron loss could be due to an inappropriate return of these cells in the cell cycle. In the present study, we observed that deprivation of neurotrophic factor in purified motoneuron cultures induces an apoptotic pathway. After neurotrophic factor withdrawal, DAPI (4,6-diamidin-2-phenylindol dichlorohydrate) staining revealed the presence of nuclear condensation, DNA fragmentation, and perinuclear apoptotic body. Similarly, release of apoptotic microparticles and activation of caspases-3 and -9 were observed within the first hours following neurotrophic factor withdrawal. Next, we tested whether inhibition of cell cycle-related cyclin-dependent kinases (cdks) can prevent motoneuronal cell death. We showed that three cdk inhibitors, olomoucine, roscovitine and flavopiridol, suppress the death of motoneurons. Finally, we observed early increases in cyclin D1 and cyclin E expression after withdrawal of neurotrophic factors. These findings support the hypothesis that after removal of trophic support, post-mitotic neuronal cells die due to an attempt to re-enter the cell cycle in an uncoordinated and inappropriate manner.

Animals↗

PubMed2005

Maintaining contact with bucks does not induce refractoriness to the male effect in seasonally anestrous female goats.

A study was performed to determine if complete separation between sexes is a pre-requisite to stimulate sexual activity of anovulatory female goats by male exposure in mid-anestrus when reproductive activity is greatly inhibited. The response to the male was studied in anovulatory goats which had either been in contact with bucks before the stimulation (n = 22; CONT), or totally isolated from bucks (n = 22; ISOL). At the time of male exposure, the bucks from the CONT groups were removed and females of both groups (CONT and ISOL) were divided into two subgroups (n = 11) exposed to novel bucks (n = 1 per subgroup), either in sexual rest (sexually inactive; SI) or in which sexual activity had been induced by a photoperiodic treatment (sexually active; SA). The sexual behavior of the SA bucks during the first 5 days of stimulation was greater than that of SI bucks (P < 0.01). Regardless of whether females had been (82%) or not (91%) exposed to bucks before teasing, most goats stimulated by SA males displayed estrous behavior and ovulation in the first 15 days following stimulation, whereas no female from the two subgroups exposed to SI bucks showed estrous behavior and only one of them ovulated (P < 0.02). These results indicate that previous isolation of seasonally anovulatory goats from bucks is not required to stimulate their reproductive activity by the male effect, if sexually active bucks are used.

Anestrus↗

PubMed2005

Estradiol receptor-alpha expression in hypothalamic and limbic regions of ewes is influenced by physiological state and maternal experience.

The influence of estrus, pregnancy, parturition, and maternal experience on the expression of estrogen receptor-alpha (ERalpha) was investigated in hypothalamic and limbic regions of the sheep brain, using immunocytochemistry. Four days before parturition, previous maternal experience was associated with a higher density of ERalpha-labeled neurons in the paraventricular and supraoptic nuclei, the medial preoptic area, and the medial amygdala, but not in the mediobasal hypothalamus. Furthermore, an interaction was found between physiological state and experience in the peripartum period as the effect of experience existing 4 days prepartum was not found at parturition, when densities were lowest both in primiparous and in multiparous ewes. An additional effect of physiological state was also observed between parturition and estrus, densities being significantly lower at parturition than at estrus in the SON, PVN, and MPOA, but not in the medial amygdala. These results indicate that in sheep ERalpha expression is influenced by previous physiological and/or maternal experience at specific times of the reproductive cycle. They are also congruent with the higher ability of multiparous than nulliparous ewes to show maternal behavior several days prepartum.

Amygdala↗

PubMed2004

Olfactory regulation of maternal behavior in mammals.

In mammals, olfactory cues are extensively used in many aspects of maternal care to ensure the coordination of mother-infant interactions and consequently the normal development of the offspring. Outside the period of parturition and lactation, when the young are not a behavioral priority, olfactory cues play an inhibitory role on maternal responsiveness since in most mammalian species studied so far, nonpregnant females find the odor of young aversive. On the contrary at the time of parturition, a shift in the hedonic value of infantile odors occurs so that the young now become a very potent stimulus and this sensorial processing constitutes an important part of the maternal motivational system. Moreover, infants' odors provide a basis for individual recognition by their mothers and some species (ungulates) have developed highly specialized mechanisms for processing of the infant signals. Perception of the smell of the young also regulates various aspects of maternal behavior. Dodecyl propionate, a compound released by of pup's preputial glands, has been shown to influence anogenital licking behavior, a fundamental pattern of maternal behavior in rodents. While there is no functional specificity of either the main or the accessory olfactory systems in the development of maternal behavior amongst species, it appears that only the main olfactory system is implicated when individual odor discrimination of the young is required. Neural structures, such as the main olfactory bulb, undergo profound changes when exposed to offspring odors at parturition. These changes in synaptic circuitry contribute both to maternal responsiveness to these odors, to their memorization, and to effects of long-term maternal experience.

Animals↗

PubMed2002

Male effect in seasonally anovulatory lactating goats depends on the presence of sexually active bucks, but not estrous females.

A study was conducted in subtropical northern Mexico (26 degrees N) to determine whether the presence of estrous females can improve the response of seasonally anovulatory goats to the introduction of bucks in the group. The induction of estrous activity was studied in three groups of anovulatory lactating goats during seasonal anestrus. These females were of the Mexican Creole breed. In the control group (sexually inactive (SI), n = 20), two control (SI) bucks exposed to normal seasonal daylength variations were used. In the second group (SI + E, n = 20 + 3), two control males were also used, but in addition, three females of the group were in estrus at the time of male introduction. In the third group (sexually active, SA + E, n = 19 + 4), anovulatory females were exposed to two bucks made sexually active by exposure to 2.5 months of long days (16L:8D) followed by two subcutaneous 18 mg melatonin implants, and four estrous females were also present when introducing the bucks. In all groups, males were introduced on 15 March and estrous detection was conducted twice daily for 15 days. The sexual activity of the bucks was observed from 08:00 to 10:00 h during the first five days of exposure to females. More females displayed estrous behavior in the first 15 days following the introduction of the males in the SA + E group (18/19) as compared with the SI or SI + E groups (2/20 and 0/20, respectively; P < 0.001). No difference was observed between the two latter groups. Thirteen females of SA + E group showed a second estrus between days 6 and 11 (short estrous cycle duration: 5.4 +/- 0.4 days). By contrast, in the SI group none showed a second estrus. The sexual behavior of the males in the SA + E group was greater as compared with that of the males in SI and SI + E groups (over 80% of the total sexual activity recorded in the three groups; P < 0.001). By contrast, no differences were found between SI and SI + E males. These results indicate that the presence of estrous females alone at the time of buck introduction is not sufficient to induce an adequate stimulation of seasonally inactive males. The use of sexually active bucks is necessary to induce reproductive activity in anovulatory females, whereas preparation of the bucks with long days followed by melatonin implants allows them to gain such a capacity.

Animals↗

PubMed2002

Twenty-four-hour-old lambs rely more on maternal behavior than on the learning of individual characteristics to discriminate between their own and an alien mother.

Lambs can discriminate their own mother from an alien dam on the first day of life, suggesting the recognition of individual physical characteristics of the mother. Alternatively, their choice may depend on behavioral differences existing between the ewes because of their maternal selectivity. To clarify this, the ability of 24-hr-old lambs to discriminate between their own and an alien mother, that were either intact and accept only their own lamb at nursing (i.e., selective, n = 19) or anosmic, which nurse indiscriminately alien lambs as well as their own (i.e., nonselective, n = 24), was assessed by a 5-min, two-choice test. With intact dams, lambs spent significantly more time next to their own mother whereas this was not so in the presence of anosmic dams. Furthermore, in the intact group, the vocal activity by their own mother differed from that by the alien dam while this was not so in anosmic ewes. We conclude that 24-hr-old lambs rely more on the behavior of the ewes to select their dam than on their individual physical characteristics.

Animals↗

PubMed2002

Induction of sexual activity in lactating anovulatory female goats using male goats treated only with artificially long days.

Two experiments were conducted to determine the response of Creole male goats treated with long days and melatonin implants, and the response of the anovulatory does to male effect using males treated only with artificially long days. All animals were allocated to open sheds. In Exp. 1, one group of males was under natural photoperiod (CG; n = 7); the second group was submitted to 2.5 mo of long days followed by the insertion of two s.c. melatonin implants (LD+MEL; n = 7); the third group was subjected only to 2.5 mo of long days (LD; n = 7). Testicular weight was measured every 2 wk. Plasma testosterone concentrations were determined weekly. A treatment x time interaction was detected (P < 0.001) for testicular weight and plasma testosterone concentration. In the LD+MEL and LD groups, testicular size and plasma testosterone levels varied in a similar way, but differed from those observed in CG (P < 0.001). In this latter group, testicular weight displayed seasonal variations and peaked in June, whereas in treated groups this peak occurred in March. In CG, testosterone varied in a seasonal manner and plasma concentrations increased in June and remained elevated throughout the study. In experimental groups, testosterone increased in February and peaked in March. In Exp. 2, one group of males was left under natural photoperiod (CG, n = 5) and the other one was submitted to 2.5 mo of artificially long days (LD, n = 4). On March 16, two control and two treated males were put in contact with 20 and 19 females, respectively. Sexual behavior of the bucks was observed during the 5 d following male introduction. Progesterone assays and estrous behavior were used to determine ovarian and behavioral responses of the females to teasing. The anogenital sniffing, nudging, and mount instances registered in LD-treated males were greater than those observed in CG (P < 0.05). Of the does exposed to CG, none ovulated and only two of 20 females displayed estrous behavior. All does in contact with LD-treated males ovulated and showed at least one estrous behavior during the 15 d following joining (P < 0.001). These results indicate that the sexual activity of male goats from subtropical latitudes can be induced using only artificially long days. In addition, males treated in this way are capable of stimulating sexual activity in anovulatory females by the male effect.

Animals↗

PubMed2001

Maternal selectivity suppression through peripheral anosmia affects neither overall nursing frequency and duration, nor lactation performance in ewes.

The effects of prepartum peripheral anosmia on nursing activity, milk production and growth of the lambs, were assessed by comparing intact (n=10) and anosmic (n=10) multiparous Columbia and Rambouillet ewes and their single lamb during the first 2 months of lactation. Intact mothers only nursed their own lamb (98%) while most of the nursing activity in anosmic mothers concerned alien lambs (78%). On the other hand, the total duration and the frequencies of nursing did not differ significantly between groups (P>0.05). Nevertheless, the total percentage of nursing of own lamb by anosmic mothers (22%) was higher than expected at random (10%). Milk production or lambs' weights did not differ between groups. We conclude that prepartum anosmia resulted in the failure of ewes to develop true selective nursing up to the 8th week of lactation, although some preferential mother-young relationship yet developed. On the other hand, it did not affect significantly overall nursing activity.

Journal Article↗

PubMed2001

The frissonnant mutant mouse, a model of dopamino-sensitive, inherited motor syndrome.

The frissonnant (fri) mutation is an autosomic recessive mutation which spontaneously appeared in the stock of C3H mice. fri mutant mice have locomotor instability and rapid tremor. Since tremor ceases when mutant mice have sleep or are anaesthetized, and because of their obvious stereotyped motor behavior, these mice could represent an inherited Parkinsonian syndrome. We show here that the fri/fri mouse fulfills two out of the three criteria required to validate an experimental model of human disease, that is isomorphism, homology and predictivity. Indeed, fri/fri mice present an important motor deficit accompanying visible tremor and stereotypies. They display some memory deficits as in human Parkinson's desease. l-Dopa and apomorphine (dopaminergic agonists), ropinirole (selective D2 agonist), and selegiline (an monoamino-oxidase B [MAO-B] inhibitor) improve their clinical status. However, neither anatomopathological evidence of nigrostriatal lesion, nor decrease in tyrosine hydroxylase production could be seen.

Animals↗

PubMed2001

Pyridoxine-induced neuropathy in rats: a sensory neuropathy that responds to 4-methylcatechol.

Sensory neuropathies are frequently associated with diabetes or with antimitotic treatments in humans suffering from cancer, and are in this case the most important limitation to the use of antimitotic drugs. For this reason, there is a need to establish and validate animal models of sensory neuropathies that could be routinely used, together with the already known models, for studying and evaluating the effects of putative neuroprotective compounds. In the present study, we prove by behavioral and electromyographical analyses that (a) it is possible to induce a nonlethal, exclusively sensory, reversible neuropathy by intoxicating rats with large amounts of pyridoxine, using a new schedule of intoxication; (b) 4-methylcatechol, a drug known to induce nerve growth factor synthesis, improves the clinical status of pyridoxine-intoxicated animals, shortens the duration of the disease, and restores the morphological integrity of the sensory fibers. Owing to its mode of installation and its clinical features, we propose that this model be used as an additional model for preclinical studies of neuroprotective drugs.

Animals↗

PubMed2001

Normal innervation and differentiation of X-linked myotubular myopathy muscle cells in a nerve-muscle coculture system.

To study the pathogenesis of X-linked recessive myotubular myopathy (XLMTM), we used a nerve-muscle coculture system which allows the reconstitution of functional motor units in vitro after coupling of human skeletal muscle cells with embryonic rat spinal cord explants. We used three skeletal muscle cell lines derived from subjects with known mutations in the MTM1 gene (two from embryonic tissues, associated with mutations predicted to give a severe phenotype, and one from a neonate still alive at 3 years 6 months and exhibiting a mild phenotype). We compared these three XLMTM muscle cell cultures with control cultures giving special attention to behaviour of living cocultures (formation of the myofibres, contractile activity, survival), expression of muscular markers (desmin, dystrophin, alpha-actinin, troponin-T, myosin heavy chain isoforms), and nerve-muscle interactions (expression and aggregation of the nicotinic acetylcholine receptors). We were unable to reproduce any 'myotubular' phenotype since XLMTM muscle cells behaved like normal cells with regard to all the investigated parameters. Our results suggest that XLMTM muscle might be intrinsically normal and emphasize the possible involvement of the myotubularin-deficient motor neurons in the development of the disease.

Animals↗

PubMed2001

Selective changes in mitochondria respiratory properties in oxidative or glycolytic muscle fibers isolated from G93AhumanSOD1 transgenic mice.

Cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in cytosolic copper, zinc superoxide dismutase (SOD1). Total SOD activity and functional mitochondrial properties were studied in muscles and nervous tissues of control and transgenic mice mimicking the disease. It was found that total SOD activity was lower in nervous tissues than in muscles in both transgenic and control mice. In addition SOD activity increased during progression of disease in muscle but not in nervous tissue of transgenic mice. Maximal oxygen consumption and apparent Km for ADP were decreased in mitochondria from transgenic soleus (an oxidative muscle). However there was no difference between control and transgenic mice in respiratory parameters of mitochondria in the EDL muscle (a glycolytic muscle). These findings indicate that oxidative stress due to SOD1 mutations could alter energy metabolism in FALS mice, thereby affecting primarily oxidative muscle of the limbs, independently of motoneuron loss.

Adenosine Diphosphate↗

PubMed2001

On the possible role of muscle in the pathogenesis of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common human inherited disease characterized by degeneration of motoneurons and muscular atrophy. SMA results from deletions or mutations of the SMN (survival motor neuron) gene. A nerve-muscle coculture model, consisting of human muscle cells innervated by rat embryonic spinal cord explants, was used to study the pathogenesis of SMA. Previous studies have shown that myotubes formed by fusion of satellite muscle cells from patients with SMA I or SMA II (but not SMA III) underwent a characteristic degeneration 1-3 weeks after innervation. To correlate this cellular study with a molecular approach, we used reverse transcriptase-polymerase chain reaction (RT-PCR), and showed that SMN mRNAs were expressed throughout the fusion of normal satellite muscle cells with two peaks, the first appearing prior to the onset of fusion and the second one or two days before innervation. When satellite muscle cells from patients with SMA I or II were used, only the first peak was observed. Because in these cases the SMN telomeric gene (SMNtel) is deleted, it was concluded that the contribution of SMNtel-dependent mRNAs to the second peak is predominant in normal myogenesis and involved in maturation of myotubes. In addition, diseased satellite muscle cells did not fuse at the same rate as normal satellite muscle cells. Studies on myf-5, a muscle specific transcription factor family, showed that its expression was impaired during the fusion of satellite muscle cells from patients with SMA I or II compared with normal satellite muscle cells. Taken together, these observations suggest that (a) there is a muscle specific expression pattern of SMN, and (b) SMN probably plays a crucial role in maintenance of a functional motor unit, by allowing muscle cells to correctly differentiate and to allow motoneuron survival.

Animals↗

PubMed2000

Cell types required to efficiently innervate human muscle cells in vitro.

Previous studies carried out in our laboratory have shown that myofibers formed by fusion of muscle satellite cells from donors with spinal muscular atrophy (SMA) type I or II undergo a characteristic degeneration 1.5-3 weeks after innervation with rat embryonic spinal cord explants. The only cells responsible for degeneration of innervated cocultures are SMA muscle satellite cells. In order to study the kinetics of nerve and muscle cell degeneration in nerve-muscle cocultures implicating SMA muscle cells, we attempted to simplify the nervous component of the coculture and identify the nerve cell types necessary for a successful innervation. We demonstrate here that motoneurons alone were unable to innervate myotubes. However, when three cell types (motoneurons, sensory neurons, and Schwann cells) were added onto a reconstituted muscular component consisting of cloned muscle satellite cells and cloned muscular fibroblasts, myotubes contracted, indicating that functional neuromuscular junctions were formed. We concluded that the three cell types were required for a successful innervation. Moreover, we studied the effects of culture medium conditioned by different combinations of nerve cells on innervation; we observed that physical contacts among sensory neurons, motoneurons, and myotubes are required for a successful innervation; in contrast Schwann cells can be replaced by a Schwann-cell-conditioned medium, indicating that these cells produce a putative soluble "innervation-promoting factor." Obviously such a reconstituted system does not reflect the in vivo situation but it allows the formation of functional motor synapses and could therefore allow us to elucidate neuromuscular disease pathogenesis, especially that of spinal muscular atrophy.

Adolescent↗

PubMed2000

Prevention of mutant SOD1 motoneuron degeneration by copper chelators in vitro.

An animal model of familial amyotrophic lateral sclerosis (FALS) has been generated by overexpression of human CuZn superoxide dismutase (SOD1) containing a substitution of glycine to alanine at position 93 in transgenic G93A mice. The loss of motoneurons shown in this model has been attributed to a dominant gain of function of this mutated enzyme, which might be due to copper toxicity. This hypothesis was tested in purified spinal motoneurons cultures originating from G93A transgenic embryos. Spinal motoneurons were isolated from E13 embryos by several steps including density gradient centrifugation. The effect of copper chelators on survival and neurite growth of motoneurons was investigated. Survival of G93A motoneurons was decreased by 46% as compared to wild-type motoneurons. Moreover, G93A motoneurons showed reduced neurite outgrowth. Copper chelators strikingly increased viability of G93A motoneurons (by over 200%) but had no effect on wild-type cells. Presence of DDC in the medium increases the length of neurites from G93A motoneurons. The present results suggest the capacity of copper chelators to reduce the effect of reverse function of mutated SOD1 on motoneurons.

Amyotrophic Lateral Sclerosis↗

PubMed2000

Male reproductive condition is the limiting factor of efficiency in the male effect during seasonal anestrus in female goats.

Two experiments were conducted to determine whether the failure of males to induce sexual activity in goats during seasonal anestrus is due to unresponsiveness of females to male stimulus or insufficient stimulation from males. In the first study, one group of males (sexually inactive, SI; n = 4) was kept under natural photoperiod while the other (sexually active, SA; n = 4) was subjected to 2.5 mo of long days (16L:8D) and received 2 s.c. implants of melatonin. Two mo later, 2 different flocks of anovulatory goats previously separated from bucks were exposed to either SI (n = 34) or SA (n = 40) bucks. Progesterone assays and estrous behavior were used to determine ovarian and behavioral responses of the females to teasing. Of the goats exposed to SI males, only 2 ovulated, and none showed estrous behavior during the 35 days of the study. In contrast, all females (40 of 40) in contact with SA males ovulated and showed at least one estrous behavior during the first 11 days following male introduction (P < 0.001). Overall, 38 of 40 females stimulated with SA bucks were diagnosed pregnant at Day 35, according to progesterone assay (versus 0 in SI-treated group: P < 0.001). To control for a possible difference of responsiveness between flocks, the experiment was repeated 1 yr later using a single flock of goats divided into 2 groups. Again, over the first 14 days, 1 of 33 goats showed estrous behavior in the SI-treated group versus 27 of 33 in the SA-treated group (P < 0.001). Therefore, treating bucks with long days and melatonin increased their teasing capacity to induce sexual activity in females during anestrus. These results indicate that the absence of response to teasing at this time of the year is not due to female unresponsiveness, but to insufficient stimulation from the male.

Animals↗

PubMed2000

Immune effects of low-dose radiation: short-term induction of thymocyte apoptosis and long-term augmentation of T-cell-dependent immune responses.

We and others have shown that low-dose X or gamma irradiation of mice leads to an increase in their survival after a subsequent lethal high-dose irradiation. The greatest increase in radioresistance appears at a fixed window of dose and time, e.g. 8 weeks after 5-10 cGy or 2 weeks after 50 cGy preirradiation. We show that low-dose irradiation induces thymocyte apoptosis with a maximal level at 6 h postirradiation that returns to background levels after 24 h. At the same time, we observed no morphological alteration of splenocytes and no early modification of the intensity of T-cell-dependent immune responses as measured by plaque-forming cell (PFC) counts. Nevertheless, we found that PFCs were increased 2 weeks after 50 cGy irradiation, which is the same time at which mice expressed the optimal increase in survival after a second lethal irradiation. We also examined thymocyte apoptosis and spleen PFCs in mice subjected to other stress-inducing pretreatments. Our results emphasize the existence of a lag time between the time of low-dose irradiation in vivo and the appearance of radioresistance. A mechanism that interconnects an environmental stimulus with the response of the animal is proposed based on the evidence presented here and reported in the literature.

Animals↗