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1.
Behav Brain Res ; 267: 133-43, 2014 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-24680988

RÉSUMÉ

BACKGROUND: Epidemiological studies have shown associations between vitamin D, mental health and glucose homeostasis in the elderly. Causal evidence, however, is still lacking. OBJECTIVE: The objective of this study was to investigate the importance of vitamin D in the prevention of emotional disturbances and cognitive decline in aging C57BL/6 mice, with pre-diabetes type II as potential effect modifier. METHODS: Mice were exposed to one of four diets from 10 months till 24 months of age: low fat vitamin D adequate (LFD), LF vitamin D deficient (LF), moderate fat vitamin D adequate (MFD), and MF vitamin D deficient (MF). The MFD/MF diet was applied to induce a condition resembling pre-diabetes type II. Behavior was assessed twice in the same group of mice at 6-8 and at 22-23 months of age using the Open Field Test (OFT), Elevated Plus Maze (EPM), Object Recognition Test (ORT) and the Morris Water Maze (MWM). RESULTS: We successfully induced vitamin D deficiency in the LF/MF mice. Moreover, fasting glucose and fasting insulin levels were significantly higher in MFD/MF mice than in LFD/LF mice. A significant aging effect was observed for most behavioral parameters. A MF(D) diet was shown to delay or prevent the age-related increase in emotional reactivity in the EPM. No effect of vitamin D or vitamin D*fat on behavioral outcomes was measured. CONCLUSION: Aging significantly affected emotional reactivity and cognitive performance. Although other studies have shown effects of vitamin D on emotional reactivity and cognitive performance in mice, these findings could not be confirmed in aged C57BL/6 mice in this study.


Sujet(s)
Symptômes affectifs/physiopathologie , Vieillissement/physiologie , Troubles de la cognition/physiopathologie , Régime alimentaire , Carence en vitamine D/physiopathologie , Animaux , Glycémie , Poids , Cognition/physiologie , Matières grasses alimentaires/administration et posologie , Émotions/physiologie , Jeûne/sang , Insuline/sang , Mâle , Apprentissage du labyrinthe/physiologie , Souris de lignée C57BL , Répartition aléatoire , /physiologie , Analyse de survie , Vitamine D/administration et posologie
2.
J Anim Sci ; 91(1): 137-46, 2013 Jan.
Article de Anglais | MEDLINE | ID: mdl-23048145

RÉSUMÉ

Feather pecking and cannibalism in farm-kept laying hens are damaging behaviors both in terms of animal welfare and economic loss, and a major challenge in modern poultry farming. Both rearing with a foster hen and genetic selection have been demonstrated to reduce feather pecking in laying hens. We examined the effects of rearing with a foster hen, genetic selection for low mortality from cannibalism, and interactions between both, using cellular morphology and levels of the rate-limiting enzyme in dopamine production, tyrosine hydroxylase, in the hippocampus and nidopallium caudolaterale (NCL) as a potential measure for laying hen welfare. Hens from the second generation of a sib-selection scheme line derived from a pure-bred White Leghorn line, selected for low mortality and for production characteristics, or their control line (CL) selected only for production characteristics, were housed with or without a foster Silky hen for the first 7 wk of life. Aside from the presence or absence of a foster Silky hen during the first 7 wk of life, housing conditions were identical for all hens. The hens were then sacrificed and brains were removed at 52 wk of age. Brains were sectioned and stained using a Nissl staining to reveal cell soma morphology, or using immunocytochemistry for tyrosine hydroxlase. A greater degree of lateralization in the hippocampus was observed in hens reared without a foster hen, as measured by absolute difference in cell soma size between hemispheres (P<0.05). The low mortality line showed decreased concentrations of tyrosine hydroxylase in the NCL compared with the CL (P<0.005). Our results indicate that morphological changes in brain induced in very early life can be detected in adult hens, and that genetic selection against mortality due to cannibalism impacts tyrosine hydroxylase in the NCL of laying hens. These observations strengthen the notion that brain measures may be useful as potential readouts for animal welfare.


Sujet(s)
Agressivité , Élevage , Comportement animal , Encéphale/cytologie , Poulets/physiologie , Tyrosine 3-monooxygenase/métabolisme , Animaux , Encéphale/enzymologie , Cannibalisme , Poulets/génétique , Femelle , Régulation de l'expression des gènes codant pour des enzymes , Oviposition , Tyrosine 3-monooxygenase/génétique
3.
Horm Behav ; 62(1): 10-7, 2012 Jun.
Article de Anglais | MEDLINE | ID: mdl-22584108

RÉSUMÉ

Brain-derived neurotrophic factor (BDNF) signaling has been implicated in the onset of depression and in antidepressant efficacy, although the exact role of this neurotrophin in the pathophysiology of depression remains to be elucidated. Also, the interaction between chronic stress, which may precede depression, corticosteroids and BDNF is not fully understood. The present study aimed at investigating whether long-lasting, recurrent tethering of sows during a period of 1.5 or 4.5 years leads to enduring effects on measures that may be indicative of chronic stress, compared with animals kept in a group housing system ('loose' sows). Immediately after slaughter, the frontal cortex, dorsal and ventral hippocampus were dissected and protein levels of BDNF and its receptors were analyzed and compared with plasma cortisol levels and adrenal weights. Results indicate that tethering stress reduced BDNF protein levels in the dorsal hippocampus and the frontal cortex, but not in the ventral hippocampus. In addition, levels of TrkB, the high affinity receptor for BDNF, were increased in the dorsal hippocampus. Plasma cortisol levels and adrenal weight were increased after tethering. These stress effects on BDNF levels were more pronounced after 4.5 years of recurrent tethering and negatively correlated in particular in the frontal cortex with cortisol levels and adrenal weight. This suggests that the stress effect of tethered housing on neurotrophin levels may be mediated via cortisol. Taken together, these data indicate that recurrent tethering stress in sows over 4.5 years results in a loss of neurotrophic support by BDNF, mediated by an overactive neuroendocrine system.


Sujet(s)
Facteur neurotrophique dérivé du cerveau/métabolisme , Lobe frontal/métabolisme , Hippocampe/métabolisme , Stress psychologique/métabolisme , Glandes surrénales/anatomie et histologie , Animaux , Dépression/métabolisme , Dépression/psychologie , Modèles animaux de maladie humaine , Femelle , Hydrocortisone/sang , Récepteur trkB/analyse , Suidae/métabolisme , Suidae/psychologie
4.
Vet J ; 192(1): 13-9, 2012 Apr.
Article de Anglais | MEDLINE | ID: mdl-21703888

RÉSUMÉ

The general concept of animal welfare embraces a continuum between negative/bad welfare and positive/good welfare. Early approaches to defining animal welfare were mainly based on the exclusion of negative states, neglecting the fact that during evolution animals optimised their ability to interact with and adapt to their environment(s). An animal's welfare status might best be represented by the adaptive value of the individual's interaction with a given environmental setting but this dynamic welfare concept has significant implications for practical welfare assessments. Animal welfare issues cannot simply be addressed by means of objective biological measurements of an animal's welfare status under certain circumstances. In practice, interpretation of welfare status and its translation into the active management of perceived welfare issues are both strongly influenced by context and, especially, by cultural and societal values. In assessing whether or not a given welfare status is morally acceptable, animal welfare scientists must be aware that scientifically based, operational definitions of animal welfare will necessarily be influenced strongly by a given society's moral understanding.


Sujet(s)
Élevage/normes , Bien-être animal/normes , Comportement animal , Animaux
5.
J Anim Sci ; 90(1): 241-51, 2012 Jan.
Article de Anglais | MEDLINE | ID: mdl-21856896

RÉSUMÉ

The possible beneficial effects of surplus dietary Trp (+5 g of Trp/kg of diet) on factors related to stress, immunology, behavior, and N retention were investigated in postweaning piglets (approximately 15 kg of BW) challenged for 10 d with intravenous bacterial lipopolysaccharide (from Escherichia coli). Two diets fed restrictively (732 kJ of NE/kg of BW(0.75)/d) were compared, 1) a basal diet (apparent ileal digestible Trp = 1.9 g/kg; the recommended amount of Trp to warrant near-optimal growth in nonendotoxemic piglets), and 2) a Trp-enriched basal diet (+5 g of free l-Trp/kg), with 8 individually housed piglets per diet. Pooled salivary cortisol, but not plasma cortisol sampled at euthanasia, showed a tendency (P = 0.07) toward reduced concentrations in the Trp group (1.1 vs. 1.4 ng/mL; pooled SE = 0.1 ng/mL). Plasma C-reactive protein was reduced (P = 0.04) in the Trp group (0.9 vs. 5.0 mg/L; pooled SE = 1.3 mg/L), but haptoglobin, IL-6, tumor necrosis factor α, and lipopolysaccharide-induced fever were similar between the 2 dietary treatments. Physical activity related to approaching a human showed a tendency (P = 0.08) toward increased latency time in the Trp group (101 vs. 60 s; pooled SE = 16 s), but the times spent standing, sitting, and lying were similar between dietary treatments. The ADFI, ADG (346 vs. 302 g/d; pooled SE = 14 g/d; P = 0.11), body N retention (11.6 vs. 11.0 g/d; pooled SE = 0.2 g/d; P = 0.18), and G:F (0.55 vs. 0.49; pooled SE = 0.03; P = 0.17) were not different between the groups fed Trp and the basal diet. In conclusion, surplus dietary Trp had limited effects on stress, immunology, behavior, and N retention in a pig model of systemic endotoxemia.


Sujet(s)
Endotoxémie/médecine vétérinaire , Escherichia coli/physiologie , Hydrocortisone/métabolisme , Lipopolysaccharides/administration et posologie , Activité motrice , Azote/analyse , Sus scrofa/croissance et développement , Tryptophane/pharmacologie , Aliment pour animaux/analyse , Animaux , Protéine C-réactive/analyse , Compléments alimentaires , Fèces/composition chimique , Mâle , Azote/urine , Stress physiologique , Sus scrofa/immunologie , Sus scrofa/physiologie , Tryptophane/administration et posologie , Tryptophane/sang
6.
Vaccine ; 29(21): 3791-801, 2011 May 12.
Article de Anglais | MEDLINE | ID: mdl-21439319

RÉSUMÉ

Active immunization against gonadotrophin-releasing hormone (GnRH) is successfully applied to prevent boar taint in pork. In men, GnRH immunization could be an alternative to hormone therapy in patients with prostate cancer. In this study, a new GnRH vaccine formulation (a modified GnRH peptide conjugate formulated with CoVaccine adjuvant) was investigated for its pharmacological efficacy and safety in young-adult male pigs. Immunization resulted in castrate-like plasma testosterone levels in all treated pigs from week 8 until the end of the study, 30 weeks after the first immunization. Testosterone depletion retarded testes growth, reduced the relative weight of the testes and accessory sex organs, and reduced sperm counts and motility. There was no clinically relevant toxicity. Typical vaccination-related adverse reactions, such as swelling at the injection site and fever, were considered acceptable. We conclude that this GnRH vaccine efficiently and rapidly reduced serum testosterone levels, without inducing chronic toxic effects, and therefore could be applicable in both veterinary and human medicine.


Sujet(s)
Hormone de libération des gonadotrophines/pharmacologie , Sus scrofa/physiologie , Vaccins/pharmacologie , Adjuvants immunologiques/pharmacologie , Animaux , Température du corps , Effets secondaires indésirables des médicaments/médecine vétérinaire , Hormone de libération des gonadotrophines/immunologie , Gonadotrophines/sang , Immunisation/effets indésirables , Immunisation/médecine vétérinaire , Mâle , Taille d'organe , Maturation sexuelle , Numération des spermatozoïdes/médecine vétérinaire , Mobilité des spermatozoïdes , Testicule/physiologie , Testostérone/sang , Urée/sang , Vaccins/effets indésirables
7.
J Chem Neuroanat ; 37(3): 141-8, 2009 May.
Article de Anglais | MEDLINE | ID: mdl-19135145

RÉSUMÉ

The aim of this study was to analyze the impact of physical and social stress on the avian forebrain morphology. Therefore, we used laying hens kept in different housing systems from puberty (approximately 16 weeks old) until the age of 48 weeks: battery cages, small littered ground pen, and free range system. Cell body sizes and catecholaminergic and serotonergic innervation patterns were investigated in brain areas expected to be sensitive to differences in environmental stimulation: hippocampal substructures and the nidopallium caudolaterale (NCL), a functional analogue of the prefrontal cortex. Our analysis shows both structures differing in the affected morphological parameters. Compared to battery cage hens, hens in the free range system developed larger cells in the dorsomedial hippocampus. Only these animals exhibited an asymmetry in the tyrosine hydroxylase density with more fibres in the left dorsomedial hippocampus. We assume that the higher spatial complexity of the free range system is the driving force of these changes. In contrast, in the NCL the housing systems affected only the serotonergic innervation pattern with highest fibre densities in free range hens. Moreover hens of the free range system displayed the worst plumage condition, which most likely is caused by feather pecking causing an altered serotonergic innervation pattern. Considering the remarkable differences between the three housing conditions, their effects on hippocampal structures and the NCL were surprisingly mild. This observation suggests that the adult brain of laying hens displays limited sensitivity to differences in social and physical environment induced post-puberty, which warrants further studies.


Sujet(s)
Encéphale/anatomie et histologie , Poulets/anatomie et histologie , Hébergement animal , Agriculture , Bien-être animal , Animaux , Encéphale/cytologie , Catécholamines/physiologie , Interprétation statistique de données , Plumes/anatomie et histologie , Femelle , Hippocampe/anatomie et histologie , Hippocampe/cytologie , Immunohistochimie , Plasticité neuronale , Cortex préfrontal/anatomie et histologie , Cortex préfrontal/cytologie , Sérotonine/physiologie , Environnement social , Stress psychologique/psychologie , Fixation tissulaire
8.
Physiol Behav ; 93(3): 453-60, 2008 Feb 27.
Article de Anglais | MEDLINE | ID: mdl-17991496

RÉSUMÉ

The aim of this study was to develop an animal model of major depression. Since two thirds of depressive patients are women, it is important to develop specific female animal models of depression. We therefore determined the consequences of chronic social defeat in individually housed prepubertal female pigs confronted with a dominant, older pig. Repeated defeat increased the salivary cortisol level, measured immediately after the confrontations, but this effect diminished after repeated confrontations. Neither organ weights nor the number of glucocorticoid (GR) and mineralocorticoid (MR) receptors in the ventral hippocampus were affected by repeated defeat. Serotonin turnover in the dorsal hippocampus was also unaffected. Behavioral analysis revealed that across confrontations, the pigs reduced the time spent actively attacking the dominant pigs, whereas the time increased in which the pigs passively underwent aggression and/or actively avoided aggression. Therefore, we conclude that the repeated social defeat paradigm does not induce long-lasting depression-like neuroendocrine effects as a consequence of behavioral adaptations (changes in the fighting strategy) in the young female pigs.


Sujet(s)
Adaptation psychologique/physiologie , Domination-subordination , Récepteurs aux glucocorticoïdes/métabolisme , Récepteurs des minéralocorticoïdes/métabolisme , Animaux , Comportement animal , Femelle , Régulation de l'expression des gènes , Hippocampe/métabolisme , Hydrocortisone/métabolisme , Salive/métabolisme , Sérotonine/métabolisme , Suidae , Facteurs temps
9.
J Vet Pharmacol Ther ; 30(5): 410-6, 2007 Oct.
Article de Anglais | MEDLINE | ID: mdl-17803732

RÉSUMÉ

We assessed the efficacy of Butafosfan, a component of Catosal, in the metaphylactic treatment of stress in pigs. Four 6-week-old female littermates were taken from 12 litters. They were confronted with a pig from a different litter for 2 h. There were 24 pairs, each consisting of confronting two unfamiliar pigs in a new pen. This housing of unfamiliar pigs provides a good, but simple, model of the psychosocial stress that pigs experience when housed in large groups on pig farms. Immediately before being housed with an unfamiliar pig, 12 pairs of pigs were injected subcutaneously with Catosal at a dose equivalent to 20 mg Butafosfan per kg body weight; the other 12 pairs received the control solution containing all ingredients of Catosal except Butafosfan. The frequency and duration of aggressive behavior and the salivary cortisol response were measured during the first 2 h of the encounter. No adverse effects associated with Catosal were observed. Subcutaneous injection of Catosal reduced the stress-induced salivary cortisol response and the frequency of aggressive behavior evoked by the social stress of housing two unfamiliar pigs together.


Sujet(s)
Animaux nouveau-nés/métabolisme , Comportement animal/effets des médicaments et des substances chimiques , Hydrocortisone/métabolisme , Composés organiques du phosphore/pharmacologie , Suidae/métabolisme , Animaux , Aire sous la courbe , Méthode en double aveugle , Femelle , Hébergement animal , Injections sous-cutanées , Phosphonates , Composés organiques du phosphore/administration et posologie , Composés organiques du phosphore/effets indésirables , Composés organiques du phosphore/pharmacocinétique , Stress physiologique/médecine vétérinaire
10.
Neurotoxicol Teratol ; 27(2): 279-97, 2005.
Article de Anglais | MEDLINE | ID: mdl-15734279

RÉSUMÉ

Putative long-term learning and memory effects of low-dose exposure to the cholinesterase inhibitor organophosphate methamidophos (Tamaron) early in life were studied in two parallel studies in middle-aged rats. Methamidophos was administered via the drinking water to female and male Wistar rats using nominal concentrations of 0 (control), 0.5, 1.5 and 4.5 ppm active ingredient for 16 weeks. Animals were then maintained for a recovery period of about 14 months without treatment. They were tested in the standard and repeated acquisition version of the Morris water escape task in two series of tests starting 33 and 55 weeks after termination of the methamidophos treatment. Functional observations and motor activity measurements preceded each series of testing. Exposure to methamidophos was confirmed by measurement of brain cholinesterase (ChE-B) at the end of the 16 weeks of treatment in satellite animals. At 4.5 ppm a biologically relevant reduction in ChE-B activity was observed without clinical signs of intoxication (males: 66%, females: 64% of control activity). Mid- and low-dose exposure to methamidophos revealed ChE-B activity of 90% and 100% in males and 88% and 97% in females, respectively. General examinations of the animals during treatment revealed no clinical signs suggesting cholinergic stimulation. Functional observations and motor activity measurements exhibited no relevant differences between treatment groups and controls. Neither the performance in the standard Morris water escape task that predominantly measures spatial reference memory, nor in the repeated acquisition task in the Morris tank, which predominantly measures spatial working memory, was affected by treatment with methamidophos. A small number of statistically significant differences were noted in the mean performance level between treatment groups, or between treatment by sex groups in both versions of the Morris task. However, these findings appeared to be idiosyncratic for a particular experiment and were not supported by findings from the other. They were consequently not considered as reflecting a consistent effect of methamidophos on learning and memory. In conclusion, administration of low doses of methamidophos to female and male Wistar rats for 16 weeks during early adulthood did not impair spatial working and reference memory in the Morris water escape task 33 and 55 weeks after cessation of treatment.


Sujet(s)
Comportement animal/effets des médicaments et des substances chimiques , Insecticides/administration et posologie , Composés organothiophosphorés/administration et posologie , Temps , Analyse de variance , Animaux , Poids/effets des médicaments et des substances chimiques , Encéphale/effets des médicaments et des substances chimiques , Encéphale/métabolisme , Cholinesterases/analyse , Relation dose-effet des médicaments , Consommation de boisson/effets des médicaments et des substances chimiques , Réaction de fuite/effets des médicaments et des substances chimiques , Femelle , Mâle , Apprentissage du labyrinthe/effets des médicaments et des substances chimiques , Mémoire/effets des médicaments et des substances chimiques , Activité motrice/effets des médicaments et des substances chimiques , Examen neurologique , Rats , Rat Wistar , Temps de réaction/effets des médicaments et des substances chimiques , Facteurs sexuels , Natation , Facteurs temps
11.
Behav Brain Res ; 156(2): 269-76, 2005 Jan 30.
Article de Anglais | MEDLINE | ID: mdl-15582113

RÉSUMÉ

The effects of the cholinesterase inhibitors (ChEI) metrifonate and donepezil were assessed on spatial performance of rats with bilateral lesions of the entorhinal cortex (EC), which is thought to model early changes in the brains of patients suffering from Alzheimer's disease. In the present study, we found that spatial discrimination deficits in rats, induced by bilateral ibotenic acid (IBO) lesions of the EC region can partially be antagonised by treatment with the cholinesterase inhibitors metrifonate (30 mg kg(-1)) and donepezil (0.3 and 3 mg kg(-1)). Performance was improved in the spatial discrimination task compared with that of the EC-lesioned control group. It is concluded that the rat with bilateral EC lesions is a suitable deficit model for the assessment of effects of putative Alzheimer therapeutics.


Sujet(s)
Troubles de la cognition/physiopathologie , Apprentissage discriminatif/effets des médicaments et des substances chimiques , Cortex entorhinal/physiopathologie , Réaction de fuite/effets des médicaments et des substances chimiques , Perception de l'espace/effets des médicaments et des substances chimiques , Trichlorfon/administration et posologie , Analyse de variance , Animaux , Comportement animal , Anticholinestérasiques/administration et posologie , Troubles de la cognition/induit chimiquement , Troubles de la cognition/traitement médicamenteux , Apprentissage discriminatif/physiologie , Relation dose-effet des médicaments , Interactions médicamenteuses , Cortex entorhinal/effets des médicaments et des substances chimiques , Cortex entorhinal/traumatismes , Réaction de fuite/physiologie , Acide iboténique/toxicité , Mâle , Apprentissage du labyrinthe , Rats , Rat Wistar , Perception de l'espace/physiologie
12.
Behav Brain Res ; 151(1-2): 37-46, 2004 May 05.
Article de Anglais | MEDLINE | ID: mdl-15084419

RÉSUMÉ

The T-maze continuous alternation task (T-CAT) assesses the spatial exploratory performance in mice. We performed a series of four experiments in order to establish the T-CAT in mice in our laboratory, to replicate published findings, and to investigate the effects of scopolamine and donepezil. In the first experiment, the task was found to be sensitive to differences between mouse strains, corroborating findings reported by Gerlai. HsdWin:CFW1 mice alternated below chance level, C57BL/6JIco and B6D2F1/JIco mice performed above chance level, and C57BL/6NTac and 129S6/SvEvTac mice performed at chance level. In the second experiment, donepezil (Aricept, E2020) at the dose of 3 mg/kg p.o. increased the rate of alternations above the level of the vehicle-treated control group in C57BL/6JIco mice, suggesting that this drug can act as cognition enhancer in normal animals. 1mg/kg scopolamine, administered intraperiteoneally (i.p.), impaired the spontaneous alternation behaviour of the mice. The slightly lower dose of 0.75 mg/kg did not affect alternation performance. The high dose of donepezil (3 mg/kg) was able to antagonise the scopolamine-induced performance deficit. With respect to time to complete a session, the results were inconclusive. In the third experiment, we found that scopolamine, administered i.p. at the dose of 1 mg/kg, or subcutaneously (s.c.) at the dose of 0.1 mg/kg, decreased the rate of spontaneous alternations in C57BL mice in the T-CAT and increased the time to complete a session. Most likely due to adverse side effects induced by the dose of 1mg/kg scopolamine, 4 out of 10 animals did not complete at least eight free-choice trials during the maximum session duration of 30min. No such adverse effects were seen after 0.1 mg/kg scopolamine, administered s.c. Finally, we evaluated whether the T-CAT yields replicable results. We conclude that the T-CAT provides a reliable tool for assessing the effects of cognition-modulating treatments in mice.


Sujet(s)
Cognition/physiologie , Comportement d'exploration/physiologie , Apprentissage du labyrinthe/physiologie , Reproductibilité des résultats , Perception de l'espace/physiologie , Analyse de variance , Animaux , Comportement animal , Comportement de choix/effets des médicaments et des substances chimiques , Comportement de choix/physiologie , Anticholinestérasiques/pharmacologie , Cognition/effets des médicaments et des substances chimiques , Donépézil , Relation dose-effet des médicaments , Voies d'administration de substances chimiques et des médicaments , Comportement d'exploration/effets des médicaments et des substances chimiques , Indanes/pharmacologie , Apprentissage du labyrinthe/effets des médicaments et des substances chimiques , Souris , Lignées consanguines de souris , Antagonistes muscariniques/pharmacologie , Pipéridines/pharmacologie , Temps de réaction/effets des médicaments et des substances chimiques , Scopolamine/pharmacologie , Perception de l'espace/effets des médicaments et des substances chimiques , Spécificité d'espèce , Facteurs temps
13.
Neuroscience ; 124(3): 523-33, 2004.
Article de Anglais | MEDLINE | ID: mdl-14980724

RÉSUMÉ

Humans suffering from subdural haematomas often show long-term cognitive dysfunctions. For identifying putative, recovery-enhancing therapeutics, animal models need to be developed in which recovery of function can be measured. For investigating whether and which type of recovery, i.e. spontaneous or training-induced recovery, or continuous partial retardation, is present in the rat model for bilateral subdural haematomas, spatial navigation abilities were assessed in the Morris water escape task in independent groups of rats at 1, 2, 4, 8, or 18 weeks after surgery. Complete spontaneous recovery seemed to occur at 8 weeks after injury. However, at 18 weeks after injury, the subdural haematoma caused a renewed deterioration of water maze performance, which was of a lesser degree than the impairments observed immediately after injury. This second phase performance deterioration was accompanied by an increase in generalised astrocyte reactivity. The rat subdural haematoma model provides an interesting tool for investigating spontaneous recovery processes of spatial navigation (8 weeks after injury), but also for progressive brain dysfunctions, considering the second phase of behavioural impairments seen at 18 weeks after injury.


Sujet(s)
Troubles de la cognition/étiologie , Troubles de la cognition/physiopathologie , Hématome subdural/complications , Récupération fonctionnelle/physiologie , Animaux , Astrocytes/cytologie , Astrocytes/physiologie , Encéphale/anatomopathologie , Encéphale/physiopathologie , Maladie chronique , Troubles de la cognition/psychologie , Études transversales , Modèles animaux de maladie humaine , Latéralité fonctionnelle/physiologie , Gliose/étiologie , Gliose/anatomopathologie , Gliose/physiopathologie , Hématome subdural/physiopathologie , Mâle , Apprentissage du labyrinthe/physiologie , Troubles de la mémoire/étiologie , Troubles de la mémoire/physiopathologie , Troubles de la mémoire/psychologie , Rats , Rat Wistar , Facteurs temps
14.
Neuroscience ; 113(2): 351-61, 2002.
Article de Anglais | MEDLINE | ID: mdl-12127092

RÉSUMÉ

The present study investigated the effects of two cyclic GMP-specific phosphodiesterase enzyme type 5 inhibitors, sildenafil and vardenafil, on the memory performance in the object recognition task. Both compounds were given per orally (1, 3 and 10 mg/kg sildenafil; 0.1, 0.3, 1 and 3 mg/kg vardenafil) immediately after the exposure to two identical objects. The memory for the objects was tested 24 h later. Vehicle-treated rats spent equal times exploring a new and the familiar object demonstrating that they did not remember the familiar one. However, sildenafil improved the object discrimination performance of the rats with a high discrimination performance at a dose of 3 mg/kg. Rats treated with vardenafil also showed an improved object discrimination performance. Compared with sildenafil, vardenafil appeared to be even more potent in this respect since it already produced a high discrimination performance at a dose of 0.3 mg/kg. The effects of both compounds on cyclic GMP and cyclic AMP accumulation were studied in rat hippocampal slices incubated in vitro. Cyclic GMP levels were increased after incubation with the highest concentration of 100 microM vardenafil (together with 0.1 mM sodium nitroprusside), although no changes in cyclic GMP levels were detected after incubation with different concentrations of sildenafil. Both compounds had no effect on cyclic AMP levels. Additional cyclic GMP immunocytochemistry showed that incubation with vardenafil (in the presence of sodium nitroprusside) resulted in a concentration-dependent staining of cyclic GMP. Staining was predominantly found in neuronal fibres in the hippocampal CA2/CA3 region. It was already detected at a concentration of 0.1 microM vardenafil. Also positive fibres were detected after incubation with sildenafil but at a higher concentration of 10 microM. Taken together, these results suggest that inhibition of phosphodiesterase enzyme type 5 improves object recognition memory. This effect might be explained by increased levels of central cyclic GMP.


Sujet(s)
GMP cyclique/métabolisme , Hippocampe/effets des médicaments et des substances chimiques , Hippocampe/métabolisme , Imidazoles/pharmacologie , Reconnaissance visuelle des formes/effets des médicaments et des substances chimiques , Inhibiteurs de la phosphodiestérase/pharmacologie , Pipérazines/pharmacologie , Animaux , AMP cyclique/métabolisme , /effets des médicaments et des substances chimiques , Immunohistochimie , Techniques in vitro , Mâle , Purines , Rats , Rat Wistar , Citrate de sildénafil , Sulfones , Triazines , Dichlorhydrate de vardénafil
15.
Genes Brain Behav ; 1(1): 9-13, 2002 Jan.
Article de Anglais | MEDLINE | ID: mdl-12886945

RÉSUMÉ

Behavioral phenotyping of mutant mice is a new and challenging task for the behavioral neuroscientist. Therefore, standardisation of the experimental conditions is required to permit comparisons between the results of experiments within and between laboratories. Once mutation-induced behavioral changes have been identified, phenotyping of mouse mutants should be performed along a systematic trajectory, which allows for an in-depth characterisation of the mutant under investigation.


Sujet(s)
Comportement animal/physiologie , Génétique du comportement , Animaux , Environnement , Souris , Souches mutantes de souris/génétique , Souches mutantes de souris/psychologie , Phénotype , Normes de référence , Reproductibilité des résultats
16.
Behav Brain Res ; 125(1-2): 3-12, 2001 Nov 01.
Article de Anglais | MEDLINE | ID: mdl-11682087

RÉSUMÉ

Behavioural phenotyping of mouse mutants is not a goal in itself but serves to characterise the behavioural effects of naturally occurring or experimentally induced mutations. Genetically engineered mouse mutants are valuable tools to elucidate the genetic control of behaviour and the interaction between genetic and environmental factors. However, a prerequisite for their use is the ability to assess different elements of behaviour. To this end, a battery of tests, which should be flexible enough to meet the needs of a particular study, should be used to characterise the behavioural phenotype. Detailed and extensive information about the effects of gene mutations is crucial for model building and model evaluation. Model building is an iterative process, switching between experimental data and theory formation. In order to facilitate this process and to allow comparison of results within and between laboratories, the standardisation of breeding, housing, and testing conditions is essential. The development and standardisation of sensitive, valid behavioural tests which are suited to phenotype mouse mutants is both a responsibility and a challenge to investigators of mouse behaviour.


Sujet(s)
Génétique du comportement , Souches mutantes de souris/génétique , Phénotype , Animaux , Génie génétique , Humains , Souris , Souris transgéniques , Modèles génétiques , Environnement social
17.
Neuroscience ; 101(1): 27-39, 2000.
Article de Anglais | MEDLINE | ID: mdl-11068134

RÉSUMÉ

Neurodegenerative diseases, traumatic brain injury and stroke are likely to result in cognitive dysfunctioning. Animal models are needed in which these deficits and recovery of the affected functions can be investigated. In the present study, the entorhinal area was chosen as the target for lesioning and for assessing the lesion-induced deficits in the Morris water maze. The entorhinal cortex is regarded as an interface between the hippocampus and neocortex. Deafferentiating the hippocampus through entorhinal lesions impairs spatial learning. The effects of lesions, induced by either electrocoagulation (experiment 1) or ibotenate excitotoxicity (experiment 2), on spatial orientation behaviour were investigated. Water maze performance after unilateral or bilateral ibotenate injections into the entorhinal cortex was studied in the third experiment. In an additional study, the replicability of the spatial learning deficit after lesions induced by bilateral injections of ibotenic acid into the entorhinal cortex was assessed by comparing the results of nine experiments. We found that spatial learning was impaired after bilateral lesions aimed at the entorhinal cortex. The electrolytic lesion technique produced a relatively large sham effect, whereas the excitotoxic lesioning method did not. Unilateral injections of ibotenic acid into the entorhinal cortex did not affect spatial navigation. The ibotenate-induced lesions replicably produced deficits in the Morris tasks. The degree of the induced spatial learning impairments and the effects on the rate of acquisition during training, however, differed between experiments. This result suggests that the fundamental biological diversity between shipments of rats can account for variation in the effects of parahippocampal damage on spatial learning even in highly standardized experimental set-ups. Rats lesioned by bilateral injections of ibotenic acid into the entorhinal cortex provide an interesting and reliable model for investigating cognitive dysfunctions in neurodegenerative diseases, stroke or traumatic brain injury.


Sujet(s)
Lésions encéphaliques/complications , Troubles de la cognition/physiopathologie , Modèles animaux de maladie humaine , Cortex entorhinal/physiopathologie , Acide iboténique/effets indésirables , Maladies neurodégénératives/complications , Accident vasculaire cérébral/complications , Lésions encéphaliques/anatomopathologie , Lésions encéphaliques/physiopathologie , Troubles de la cognition/induit chimiquement , Troubles de la cognition/anatomopathologie , Cortex entorhinal/effets des médicaments et des substances chimiques , Cortex entorhinal/anatomopathologie , Latéralité fonctionnelle/effets des médicaments et des substances chimiques , Latéralité fonctionnelle/physiologie , Apprentissage du labyrinthe/effets des médicaments et des substances chimiques , Apprentissage du labyrinthe/physiologie , Maladies neurodégénératives/anatomopathologie , Maladies neurodégénératives/physiopathologie , Performance psychomotrice/effets des médicaments et des substances chimiques , Performance psychomotrice/physiologie , Récupération fonctionnelle/physiologie , Reproductibilité des résultats , Accident vasculaire cérébral/anatomopathologie , Accident vasculaire cérébral/physiopathologie , Natation/physiologie , Facteurs temps
18.
Neuropharmacology ; 39(5): 817-34, 2000 Mar 03.
Article de Anglais | MEDLINE | ID: mdl-10699447

RÉSUMÉ

Twenty per cent of all strokes are haemorrhagic in character and are associated with severe disturbances in sensorimotor behaviour and cognition. Although spontaneous recovery of pre-stroke functioning occurs in some cases, the process is demanding, slow, and often incomplete. A first step in the preclinical testing of new putative, neuroprotective and recovery-supporting therapeutics is to validate animal models of brain injury. In a series of four experiments we evaluated the behavioural impairments and the time course of recovery of functional deficits in rats with an experimentally induced subdural haematoma. We found that unilateral subdural haematoma resulted in dysfunction in both simple reflexive (experiment 1) and skilled sensorimotor behaviour (experiment 2). Reflexive behaviour did not recover, or recovered only marginally, and neither did the deficits in skilled forepaw use. Bilateral subdural haematoma impaired the learning and memory performance of adult (experiment 3) and old rats (experiment 4) in the Morris water escape task. Considering the diversity of the deficits found in our experiments, we conclude that different models are needed to cover the broad range of deficits seen in stroke patients.


Sujet(s)
Hématome subdural aigu/physiopathologie , Apprentissage du labyrinthe , Performance psychomotrice , Perception de l'espace , Facteurs âges , Animaux , Comportement animal/physiologie , Corps calleux/anatomopathologie , Croisements génétiques , Modèles animaux de maladie humaine , Réaction de fuite/physiologie , Membre thoracique/physiologie , Hématome subdural aigu/anatomopathologie , Membre pelvien/physiologie , Mâle , Apprentissage du labyrinthe/physiologie , Cortex moteur/anatomopathologie , Cortex moteur/physiopathologie , Performance psychomotrice/physiologie , Rats , Rats de lignée BN , Rats de lignée F344 , Rat Wistar , Temps de réaction/physiologie , Réflexe/physiologie , Cortex somatosensoriel/anatomopathologie , Cortex somatosensoriel/physiopathologie
19.
Physiol Behav ; 68(4): 599-602, 2000 Feb.
Article de Anglais | MEDLINE | ID: mdl-10713304

RÉSUMÉ

The spatial orientation of mice and rats in tasks such as the Morris water escape task is guided by extramaze cues. Using data from the control groups of mice used in two drug-finding experiments, we addressed the question whether the size of the Morris water tank affects spatial learning in mice. In these experiments, CFW1 mice had been tested in either a small or a large water tank. Reanalysis of the data revealed that pool size did not affect learning or bias for the previous training quadrant. The Morris water escape task appears to act as a severe stressor in particular mouse strains, and a high stress level may interfere with the learning ability or performance of mice, which may have serious consequences for the interpretation of data. This is of special relevance when assessing the Morris maze performance of strains of mice with a different sensitivity to stress. We conclude that mice can best be tested in a small pool, because the time and distance swam to find and escape onto the platform is decreased and the probability of success (that is, of encountering the platform) is increased. This will reduce stress and hence increase the comparability of data between different strains of mice.


Sujet(s)
Apprentissage discriminatif/physiologie , Apprentissage du labyrinthe/physiologie , Psychologie expérimentale/instrumentation , Perception de l'espace/physiologie , Animaux , Mâle , Souris , Lignées consanguines de souris , Natation/psychologie , Enregistrement sur bande vidéo
20.
Neuroscience ; 94(2): 373-88, 1999.
Article de Anglais | MEDLINE | ID: mdl-10579201

RÉSUMÉ

Although memory deficits are one of the most persistent consequences of human subdural haematoma, cognitive functioning has hardly been investigated in the rat subdural haematoma model. In the present study, the effects on spatial learning of right- and left-sided unilateral subdural haematoma and of bilateral subdural haematoma induced above the sensorimotor cortical areas were evaluated. Spatial learning was assessed by standard acquisition in the Morris water escape task (five sessions). Additional issues addressed were sensorimotor functioning (footprint analysis), recovery of cognitive functioning (tested by an overtraining and a reversal training) and replicability of induced cognitive deficits. Following unilateral subdural haematoma surgery, hardly any impairments in the Morris water escape task were observed: rats with a unilateral right-sided subdural haematoma showed very mild, transient deficits, whereas rats with left-sided subdural haematoma were indistinguishable from controls. Bilateral subdural haematoma surgery led to a clear, although transient, performance deficit. We conclude that animals with bilateral subdural haematoma may provide a promising cognitive deficit model for investigating recovery of function.


Sujet(s)
Réaction de fuite/physiologie , Hématome subdural/psychologie , Apprentissage du labyrinthe/physiologie , Animaux , Troubles de la cognition/étiologie , Troubles de la cognition/physiopathologie , Latéralité fonctionnelle , Démarche , Hématome subdural/physiopathologie , Humains , Mâle , Activité motrice , Rats , Rat Wistar , Cortex somatosensoriel/physiologie , Cortex somatosensoriel/physiopathologie , Perception de l'espace
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