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Biomedical subjects

C Joubert

Publications and source records attributed to C Joubert.

At least 19 recordsLinked to original sources

Long-term treatment with the antioxidant drug EGb 761 at senescence restored some neurobehavioral effects of chronic ultramild stress exposure seen in young mice.

In this study, we compared the effects of chronic ultramild stress (CUMS) exposure on decision-making behavior in a validated test, and on the stress responsive serotoninergic and dopaminergic systems in four age groups of B6D2F1 female mice (5-6, 11-12, 17-18 and 23-24 months old). The levels of serotonin (5-HT) and its metabolite 5-hydroxyindolacetic acid (5-HIAA) were measured in the brain stem, the cortex, the striatum and the hippocampus; the levels of dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) were measured in the brain stem and the striatum. The influence of a long-term treatment with the extract of Ginkgo biloba leaves EGb 761 (Tanakan) on age- and stress-related changes was also investigated in the two oldest age groups. In the absence of drug treatment, middle-age mice were the least efficient in making a decision, and senescent mice exhibited reduced levels of both 5-HT and DA and their metabolites in all the brain areas examined. CUMS facilitated evaluation and choice behavior in all age groups, but induced age-dependent reduction of hesitation, acceleration of information processing and reduction in serotoninergic neurotransmission. In senescent mice, EGb 761 reduced the impact of stress on evaluation and hesitation, and restored some stress-related neurobehavioral changes that were only seen in young mice, i.e. acceleration of information processing and reduction in brain 5-HIAA levels. Restoration of some plasticity of the serotoninergic systems might contribute to the stress alleviating influence of EGb 761 in old age.

3,4-Dihydroxyphenylacetic Acid↗

Effects of adrenal medulla graft on recovery of GABAergic and dopaminergic neuron deficits in mice: behavioural, pharmacological and immunohistochemical study.

We studied the capacity of adrenal medullary transplant to restore the deficits of GABAergic and dopaminergic neurons in mice injected with quinolinic acid (QA), using an open field test as well as pharmacological and immunohistochemical techniques. We analysed behavioural traits-total locomotor activity, peripheral and central activities, grooming, leaning and rearing in the QA-lesioned mice and mice that had undergone adrenal medulla (AM) transplantation. We found that the adrenal transplant recovered a loss of GABAergic neurons. It reduced QA-induced hyperactivity in locomotion and improved emotional indices. In addition, immunohistochemical studies of catecholaminergic markers-tyrosine hydroxylase (TH), dopamine (DA) and neuronal vesicular monoamine transporter type 2- and a single post-trial injection of tetrabenazine (TBZ; 5 mg/kg) indicated that catecholamines-synthesising chromaffin cells in the AM grafts were also involved in the beneficial effects. A likely interpretation of this behavioural pattern of results is that adrenal medullary transplants set into play an interaction between GABAergic and DAergic factors. Our results may contribute to the clarification of the beneficial effects of AM transplants in striatal function.

Adrenal Medulla↗

Alterations in water and electrolyte absorption in the rat colon following neutron irradiation: influence of neutron component and irradiation dose.

PURPOSE: To study the absorptive function of rat colon following whole-body exposure to neutron irradiation, either to the same total dose with varying proportion of neutrons or to the same neutron proportion with an increasing irradiation dose. MATERIALS AND METHODS: Different proportions of neutron irradiation were produced from the reactor SILENE using a fissile solution of uranium nitrate (8, 47 and 87% neutron). Water and electrolyte fluxes were measured in the rat in vivo under anaesthesia by insertion into the descending colon of an agarose gel cylinder simulating the faeces. Functional studies were completed by histological analyses. In the first set of experiments, rats received 3.8 Gy with various neutron percentages and were studied from 1 to 14 days after exposure. In the second set of experiments, rats were exposed to increasing doses of irradiation (1-4Gy) with a high neutron percentage (87%n) and were studied at 4 days after exposure. RESULTS AND CONCLUSIONS: The absorptive capacity of rat colon was diminished by irradiation at 3-5 days, with a nadir at 4 days. The results demonstrate that an increase in the neutron proportion is associated with an amplification of the effects. Furthermore, a delay in the re-establishment of normal absorption was observed with the high neutron proportion (87%n). A dose-dependent reduction of water absorption by rat colon was also observed following neutron irradiation (87%n), with a 50% reduction at 3 Gy. Comparison of this dose-effect curve with the curve obtained following gamma (60)Co-irradiation indicates an RBE of 2.2 for absorptive colonic function in rat calculated at 4 days after exposure.

Absorption↗

Involvement of adrenal medulla grafts in the open field behavior.

Immunohistochemical and behavioral techniques were used to study the effects of adrenal medulla grafts, implanted in striatum after bilateral kainic acid (KA) lesions of this structure, on the open field behavior of mice. KA-induced behavioral changes in leaning, grooming and locomotor activity of the open field test were significantly improved after grafting of the adrenal medulla, and in some respects, fully restored. Immunohistochemical identification showed that grafts contained neuron-like cells with a tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase, gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), and enkephalin-like immunostainings. A likely interpretation of this complex pattern of results is that adrenal medullary grafts may restore the deficits of GABAergic neurons which in turn reverse the abnormalities in emotionality and locomotion. Neurobiologically, these behavioral improvements probably involve GABAergic and catecholaminergic factors of adrenal medulla grafts, although other neuroactive substances, such as acetylcholine and enkephalins, cannot be excluded.

Adrenal Medulla↗

Level of Flt3-ligand in plasma: a possible new bio-indicator for radiation-induced aplasia.

PURPOSE: To follow plasma Flt3-ligand (FL) concentrations in irradiated animals in order to evaluate it as an indicator of bone marrow damage for the management of accidental radiation-induced aplasia. MATERIALS AND METHODS: Non-human primates were irradiated at doses ranging from 2 to 8 Gy, using whole- or partial-body irradiation. Plasma FL concentrations and blood cell counts were determined daily. RESULTS: FL concentrations increased as early as day 2 after irradiation, whatever the irradiation dose. Increase in plasma FL concentration on day 5 post-irradiation was correlated with radiation dose and with the severity of radiation-induced aplasia. During the course of aplasia, FL concentrations in plasma were inversely correlated with neutrophil counts. A peak in FL concentration appeared before the neutrophil nadir, and the subsequent decrease in FL concentration was correlated with the recovery of blood-cell populations. CONCLUSIONS: Monitoring plasma FL concentration can be used as an indicator of radiation-induced marrow aplasia, and this may be of use in accidental irradiation situations.

Animals↗

Balance control and posture differences in the anxious BALB/cByJ mice compared to the non anxious C57BL/6J mice.

A relation between anxiety disorders and balance control dysfunctions has been observed in many studies in humans. A mismatch in the integration of sensory inputs could trigger these disturbances. Very few experimental animal procedures have been designed to study the functional link between anxiety and balance control. A task was therefore developed, challenging the visual, vestibular and somesthesic sensory systems in mice. The test, called the 'rotating beam', gave an accurate assessment of balance control and the posture, using sensitive measures (number of falls and imbalances, position of tail and trunk). Striking differences were observed between the two inbred strains of mice known to have radically different anxiety-related behaviour. The highly anxious strain, BALB/cByJ, performed poorly compared to the non anxious strain, C57BL/6J. Balance control and postural abilities of anxious mice were improved by acute anxiolytic diazepam treatment. Lower behavioural performance level was registered in non anxious mice given anxiogenic beta-CCM treatment. The findings account for a strong relationship between anxiety and balance control in mice. Finally, the highly sensitive procedure proved to be well suited to the study of functional links between anxiety and sensorimotor processes.

Animals↗

A comparison of jump performances of the dog flea, Ctenocephalides canis (Curtis, 1826) and the cat flea, Ctenocephalides felis felis (Bouché, 1835).

Jump performances of Ctenocephalides canis and Ctenocephalides felis felis have been measured and compared on unfed young imagos. The mean length of the C. felis felis jump was 19.9+/-9.1cm; minimum jump was 2cm, and the maximum was one 48cm. The C. canis jump was significantly longer (30.4+/-9.1cm; from 3 to 50cm). For height jump evaluation, grey plastic cylindric tubes measuring 9cm in diameter were used. Their height was increasing from 1 to 30cm by 1cm. Groups of 10 fleas of the same species were deposited on the base of the tube. The number of fleas which succeeded in jumping above the tube was recorded. The mean height jump carried out by 50% of fleas was calculated after linearisation of the curves: it was 15.5 and 13.2cm for C. canis and C. felis, respectively. The highest jump was 25 for C. canis and 17cm for C. felis.

Animals↗

Influence of prepartum chronic ultramild stress on maternal pup care behavior in mice.

BACKGROUND: Stress administered to pregnant rodents has been shown to lead to biological and behavioral alterations in both mother and pups. Most of these stress procedures use noxious stressors. Chronicity is obtained by simple repetition of one or two stressors and may be more representative of moderate daily stress experienced during normal life than stress during severe life events. The effects of this procedure were assessed by observing maternal pup-care behavior and testing maternal aggression. METHODS: The subjects included eight controls and eight stressed B6D2F1 females. Chronic ultramild stress was applied from mating to postpartum day (PD) 0. Pup-care behavior was observed on PD 1. Maternal aggression against a male intruder was tested on PD 8, which corresponds to the peak in the display of this behavior. RESULTS: Prenatal stress did not affect basic pup-care behavior, but dramatically impaired defense behavior designed to protect the pups from an external attacker. CONCLUSIONS: The results suggest that gestating females subjected to chronic ultramild stress suffer from a long-lasting decline in recognition of external distress cues either from a resident intruder and/or their own litter. It is assumed these effects are due to the chronicity of the stress rather than its severity.

Animals↗

In vivo regulation of cerebral monoamine oxidase activity in senescent controls and chronically stressed mice by long-term treatment with Ginkgo biloba extract (EGb 761).

It is well recognized that Ginkgo biloba extract (EGb 761) exert beneficial effects against various age-related changes and is able to reduce the negative influence of stress. In view of the age-dependent increase in the activity of the B form of monoamine oxidase (MAO-B) and in view of the anti-stress action of EGb 761 hypothetically attributed to an inhibition of monoamine oxidase by this substance, we investigated the effects of long-term treatment with EGb 761 upon in vivo cerebral MAO-A and -B activities of stressed and unstressed 17- and 18-month-old mice. The stress was a 'chronic mild stress' regimen whose behavioral impact is known to be reduced by EGb 761. The results showed that: (1) EGb761 induced reductions in MAO activity in 18-month-old, but not in 17-month-old mice; the older animals having higher basal MAO activity; (2) in unstressed mice, EGb 761 appeared to reduce the age-induced increase in cerebral MAO activity; (3) MAO-A and -B activities of stressed and treated 18-month-old mice did not differ significantly from the levels observed in unstressed and untreated 17-month-old mice. These results may shed light on the anti-stress effects of Ginkgo biloba extract.

Aging↗

Differences in anxiety-related behavior and response to diazepam in BALB/cByJ and C57BL/6J strains of mice.

The study in an ethological perspective of inbred strains of mice offers a more accurate description of anxiety-related behavior. In this context, behavioral performances of the BALB/cByJ and C57BL/6J strains were systematically compared in the staircase test, the light/dark test and the elevated plus maze test. A rarely used variable, the latency of the first entry in the dark box, was also recorded in the light/dark test. A new statistical approach to this measure meant that specific avoidance strategies could be differentiated in the two strains. A study of the behavioral responses of the two strains given treatment with diazepam, a widely used anxiolytic compound, was also carried out. Results showed substantial differences between BALB/cByJ and C57BL/6J strains. C57BL/6J mice had high baseline activity and exploration of a new environment, suggesting a low level of anxiety. BALB/cByJ mice displayed defensive and protective behavior, with limited exploration of the new environment together with low locomotor activity. The response to diazepam was also different for each strain: C57BL/6J mice showed higher sensitivity to diazepam treatment than did BALB/cByJ mice.

Animals↗

Influence of a chronic ultramild stress procedure on decision-making in mice.

OBJECTIVE: To test the influence of a chronic ultra mild stress (CUMS) procedure, based solely on socio-environmental stressors, on cognitive-behavioural function in mice. DESIGN: Behavioural study. PARTICIPANTS: B6D2F1 mice. INTERVENTIONS: Mice were exposed to various stressors and then tested using a decision-making task. RESULTS: We observed that stress facilitated "choice" behaviour, with an absence of "no choice" behaviour. Stress also facilitated a more rapid capacity to process information, a decrease in the level of evaluation of the choice situation and less hesitation. These stress-related consequences on decision making may be attributed to a higher level of distractability in the stressed mice. CONCLUSIONS: The CUMS model may be useful for the study of stress-related disorders by proposing a new method for assessing gene-environment interactions in cognitive-affective behaviours.

Animals↗

5-HT1A autoreceptor desensitization by chronic ultramild stress in mice.

Electrophysiological and biochemical approaches were used to assess possible changes in central 5-HT neurotransmission in mice that had been subjected to chronic ultramild stress for 8 weeks. This treatment produced a significant decrease in the potency of the 5-HT1A agonist ipsapirone to inhibit the electrical activity of serotoninergic neurons in the dorsal raphe nucleus, without modifying 5-HT1A receptor binding in various brain areas. These data demonstrate that chronic ultramild stress triggers a long term and durable functional desensitization of somatodendritic 5-HT1A autoreceptors in mice.

Action Potentials↗

Biochemical indicators of whole-body gamma-radiation effects in the pig.

PURPOSE: Validation of the pig as an experimental animal model for dose assessment after ionizing irradiation. MATERIALS AND METHODS: The evolution of haematological and biochemical parameters was followed for up to 7 days after irradiation in pigs exposed to whole-body 60Co gamma-radiation at doses between O and 6 Gy. RESULTS: Some biochemical indicators showed significant variations: amylase, LDH, alkaline and acid phosphatases, ALT and iron. None of the studied parameters alone presents a reliable dose-effect relationship; however, there was evidence that the combination of lymphocyte and neutrophil counts and the determination of LDH, ALT, AST and urea levels allowed some dose determination, independent of time, if blood samples were taken within 7 days post-irradiation. CONCLUSION: The results confirm the main problems of biochemical dosimetry. However, the pig model could represent a useful alternative to the non-human primate in radiobiology research, especially in the case of partial-body exposure. A multiparametric approach to dose assessment seems to be possible in the pig model. Confirmation should be carried out using blood samples from patients undergoing radiotherapy treatment.

Acid Phosphatase↗

Modified bile acid profiles in mixed neutron and gamma-irradiated pigs.

PURPOSE: To determine the effect of mixed neutron and gamma-irradiation on the bile acid pool, which may be a key factor in radiation-induced diarrhoea. MATERIALS AND METHODS: The bile duct of pigs was catheterized to derive bile over several experimental weeks, both before and after a 5.9 Gy neutron and gamma-irradiation. After measurement of the volume and sampling, bile was returned to the pig via a duodenal catheter. Samples of bile were analysed by HPLC for their individual and total bile acid content. Blood samples were also collected for total bile acid determination. RESULTS: Bile flow was significantly decreased during the first 24h and after the fifth day post-irradiation. Whereas total bile acid concentration in bile was not altered, profiles of individual bile acids were significantly altered as early as the first post-irradiation day. Such modifications in these profiles resulted in a change of the properties of the bile acid pool. An increased proportion of dihydroxylated bile acids known to be more deleterious for the intestine was observed. CONCLUSIONS: Neutron and gamma-irradiation leads to modifications of bile acid profiles, which may partly explain radiation-induced diarrhoea by a coherent physiopathological mechanism.

Animals↗

Whole-body gamma irradiation modifies bile composition in the pig.

The effects of 6 Gy whole-body 60Co gamma irradiation on bile composition in pigs were studied to determine possible alterations in the quality of the bile, which may be a determining factor in diarrhea as well as nutrient malabsorption, which classically occurs after irradiation. The bile duct of pigs was catheterized to allow a total and continuous deviation of bile over several weeks, before and after irradiation. After measurement of the volume and sampling, bile was returned to the animal via a duodenal catheter. Bile samples were then analyzed for cholesterol, phospholipid and total bile acid content. Individual bile acids were quantified by HPLC analysis. Bile flow was significantly decreased during the first 24 h and after the fifth day postirradiation. Whereas cholesterol, phospholipid and total bile acid concentrations were not altered, profiles of individual bile acids were modified significantly as early as the first day postirradiation. Moreover, the change of these profiles with time was specific for each bile acid. Such modifications in bile acid profiles resulted in a change in the properties of the bile acid pool in an increased proportion of dihydroxylated bile acids known to interfere with gut functions, and it is reasonable to suggest that radiation-induced changes in bile acid profiles may be involved in radiation-induced gastrointestinal disorders.

Animals↗

Exposure to either gamma or a mixed neutron/gamma field irradiation modifies vasoactive intestinal peptide receptor characteristics in membranes isolated from pig jejunum.

The effect of acute whole body exposure to ionizing radiation was investigated on intestinal vasoactive intestinal peptide (VIP) receptors and adenylate cyclase activity in membranes isolated from pig jejunum. Pigs under light anaesthesia were exposed to a single dose (6 Gy) of gamma (gamma) or to mixed neutron/gamma field (ratio 1:1; neutron/gamma) irradiation. Seven days after irradiation, plasma-membranes were prepared from post mortem jejunal mucosal scrapings. Marker enzyme activities (sucrase, leucine aminopeptidase (LAP), Na,K-ATPase) were measured in each preparation. The characteristics (KD, Bmax) of VIP receptors were determined using 125I-labelled VIP. In addition VIP-sensitive adenylate cyclase activity was measured. Results showed that enzyme activities were reduced following both gamma (sucrase 67%; LAP 53%; Na/K-ATPase 29%; N = 7) and neutron/gamma (sucrase 53%; LAP 59%; Na/K-ATPase 68%; N = 5) compared with control values (N = 5). VIP receptor affinity was decreased following either type of irradiation (gamma or neutron/gamma P < 0.01) and receptor numbers increased. Both VIP- and forskolin-stimulated adenylate cyclase activities were reduced but the sensitivity of the enzyme remained the same for VIP (EC50 values (nmol dm-3)-control-1.27 +/- 0.35; gamma-2.18 +/- 0.41; neutron/gamma-1.91 +/- 0.28). In conclusion, exposure to either gamma or neutron/gamma irradiation attenuates intestinal enzyme activities and VIP receptor affinity but increases VIP receptor numbers.

Adenylyl Cyclases↗