Biomedical subjects

J Caston

Publications and source records attributed to J Caston.

At least 37 records · Page 2Linked to original sources

PubMed1997

Fear decrease in transgenic mice overexpressing bcl-2 in neurons.

Neuronal destruction in the amygdala, hypothalamus and cerebellum provokes a diminution in anxiety and neophobia. In transgenic mice that express the human bcl-2 gene under the control of neuron specific enolase promotor (Hu-bcl-2), BCL-2 overexpression reduces the naturally occurring neuronal death, producing an increase of the number of neurons and brain size. Since BCL-2 over-expression has been observed in different parts of the brain and especially in the amygdaloid nuclei, the hypothalamus and the cerebellum, we studied the fear-related behavior of these transgenic mice. Hu-bcl-2 transgenic mice showed a decrease in anxiety and neophobia, indicating that, for this particular behavior, supernumerary neurons elicit the same modification as that observed after neuronal destruction.

Animals↗

PubMed1997

Effect of cerebellar granule cell depletion on spatial learning and memory and in an avoidance conditioning task: studies in postnatally X-irradiated rats.

Rats of the DA/HAN strain (pigmented rats) were submitted to two experimental tasks consisting in spatial learning (water escape experiment) and in passive avoidance conditioning. These rats were either totally or partially deprived of their granule cells using two different schedules of postnatal X-irradiation of the cerebellum. When they were 3 months old, the animals were submitted to an initial learning session, followed by a retrieval test seven days later. The scores of the rats which were partially deprived of granule cells appeared similar to those of controls, except for a mild deficiency of spatial learning. The learning and retrieval scores of the rats totally deprived of granule cells were similar to those of controls at the passive avoidance conditioning task, but these animals were unable to accurately learn a spatial task and showed memory impairments relative to controls. These results are discussed in terms of cognitive defects.

Animals↗

PubMed1997

Impaired motor skills on static and mobile beams in lurcher mutant mice.

The cerebellum plays a role in various sensorimotor learning tasks. The purpose of the present studies was to evaluate sensorimotor skills in a spontaneous mouse mutant with cerebellar cortical atrophy. Lurcher mutant mice, characterized by massive losses of cerebellar granule cells and Purkinje cells, were assessed on two static beams varying in width and on an accelerating rotorod. On the static beams, lurcher mutants were deficient in stable positioning while immobile. Contrary to normal mice, they retreated backwards involuntarily and clung off-balance to the side of the beams. However, lurcher mutants were not deficient in segment crossings, body turns, latencies before crossing the first segment, and time spent in motion. There was an improvement over days in static stable positioning on both beams. On the rotorod, although lurcher mutants fell sooner and were inferior to controls in maximal speed of rotation achieved, there was an improvement on both measures across days. Moreover, retention of this motor skill was normal. These results indicate that, although lurcher mutants are limited in their capacity to execute motor coordination tasks, postural sensorimotor learning is not abolished in the absence of cerebellar cortical output neurons.

Animals↗

PubMed1997

Influence of olfactory stimulation on nociceptive behavior in mice.

The reactions elicited by nociceptive stimulations were studied in mice exposed to the presence of different odors: positive (attractive), negative (aversive), or neutral. In a first set of experiments, the animals were not habituated to the odors before the nociceptive stimuli were applied; in this case, the olfactory environment during experienced pain had essentially no effect on the nociceptive reactions, whatever the nature of the odors. In a second set of experiments, the animals were habituated to the same odor for 20 days. The control group consisted of mice habituated to and tested in the presence of the odor of the laboratory. In that case, compared to controls, the neutral odor had no influence on nociceptive reactions. By contrast, the positive odor decreased and the negative odor increased the reactions, especially when the intensity of the nociceptive stimulus was low. Moreover, it has been shown that the reactions elicited during a second nociceptive stimulation period depend on the perception of pain animals experience during the first stimulation, which depended, in turn, on the odor associated with it. Results are discussed in terms of opioid-mediated interactions between olfaction and pain.

Animals↗

PubMed1997

Acute stress in pregnant rats: effects on growth rate, learning, and memory capabilities of the offspring.

Growth rate of the offspring of female rats stressed by the presence of a cat at the 10th or the 19th gestational day was lower than that of controls whereas footshocks administered at the same periods did not significantly influence growth rate of the young. Whatever the nature of the stress and the time when it was administered to the mother, the death rate of the young rats was much greater than that in controls. When adult, the offspring of stressed mothers exhibited learning and memory impairments in a delayed alternation task as well as in passive avoidance conditioning. Alteration of these cognitive functions is interpreted in terms of subtle dysfunctions in the development of the nervous system through modifications of the hormonal components of the mothers, particularly eventual alterations of the nervous system biochemistry of the offspring.

Animals↗

PubMed1997

Role of the inferior olivary complex in motor skills and motor learning in the adult rat.

The inferior olivary complex of adult rats was chemically destroyed using intraperitoneal injection of 3-acetylpyridine. Animals were submitted to different motor tasks: hanging test, equilibrium test and motor co-ordination test. The different scores show that 3-acetylpyridine-treated rats had motor co-ordination and static equilibrium deficiencies, whereas their rod suspension capabilities were intact. Animals were also trained on an unrotated rod or on a rod rotating at 5, 10 or 20 r.p.m. 3-Acetylpyridine-treated rats were able to maintain their equilibrium on the unrotated rod and at 5 r.p.m. Moreover, after motor training at 5 r.p.m., rats were able to improve their motor skills and reached the same score as controls. Despite their good motor skills, animals were unable to maintain their equilibrium when rotated at 10 and 20 r.p.m. These results suggest that the inferior olivary complex is needed for motor learning involving the temporal organization of movement.

Age Factors↗

PubMed1997

Hypothesis: the meeting place model for prion disease.

Prions are responsible for spongiform diseases such as scrapie and bovine spongiform encephalopathy. It is now generally accepted that the disease mechanism involves the conversion from the normal form, PrPC, to the pathogenic form, PrPSc, and that this isoform is infectious. In the case of scrapie, 15 different forms of the disease have been described and some of these different phenotypes can be conferred by infectious prions that are themselves encoded by normal genes. We propose here that a prion with an altered structure has a correspondingly altered preference for lipids; this altered preference creates a proteolipid domain containing different lipids and other factors such as chaperonins and enzymes responsible for post-translational modifications. Normal prions associated with this abnormal domain adopt the conformation dictated by its lipidic composition (and by the other factors present) and so acquire the lipidic preference of the original pathogenic prions. These transformed prions could then create new proteolipid domains. This process may be considered as semi-conservative replication in which prion and lipids are analogous to the Watson and Crick strands and the proteolipid domain to the double helix itself.

Animals↗

PubMed1997

Delayed spontaneous alternation in intact and cerebellectomized control and lurcher mutant mice: differential role of cerebellar cortex and deep cerebellar nuclei.

Lurcher mutant (+/Lc) mice exhibit a massive loss of neurons in the cerebellar cortex and in the inferior olivary nucleus while deep cerebellar nuclei are essentially intact. To discriminate the respective participation of the cerebellar cortex and deep structures in learning and memory, the authors subjected 3- to 6-month-old +/Lc mice to a delayed spontaneous alternation task to test their working and long-term spatial memories. Results show that wild type (+/+) mice alternated above chance even after a 1-hr delay between the forced and choice trials, whereas in +/Lc mice, long-term memory was impaired. Cerebellectomized +/+ mice behave as +/Lc mice (working memory was preserved but long-term memory was not), whereas in the cerebellectomized +/Lc mice, both working and long-term memories were altered. These results are discussed in terms of relationships between the cerebellum and the hippocampus.

Animals↗

PubMed1997

Effect of cerebellar granule cell depletion on learning of the equilibrium behaviour: study in postnatally X-irradiated rats.

To assess the role of the mossy fibre-granule cell pathway in learning, the cerebellum of young DA/HAN strain rats was irradiated to make the cortex completely or partially agranular. The X-rays were delivered according to two different schedules, between 5-14 postnatal days (early group) and between 10-14 postnatal days (late group). Histological controls at 35 days showed a mean loss of granule cells of 96 +/- 1% in the early group and of 61 +/- 3% in the late group. The irradiated animals were subjected, from day 23 to day 35, to daily sensorimotor training on a rotorod. The scores and the strategy used (walking or hanging) by the rats were noted. The results demonstrate that a partial loss of granule cells due to a late X-irradiation schedule induced mild motor disabilities but no learning deficit, the only problem being difficulty in elaborating rapidly an efficient strategy to solve a novel problem. A sub-total loss of the granule cells, due to an early X-irradiation schedule, induced gross motor disabilities and the animals used hanging > 90% of the time. Due to the discrepancy between the learning abilities, which were preserved at least in part, and the gross motor impairments, the animals elaborated a novel strategy (jumping from the beam), allowing them to escape the experimental situation. This avoidance behaviour may be due to a decrease of anxiety, a lack of behavioural inhibition and/or attentional deficits that have been already observed in several other examples of cerebellar abnormalities.

Aging↗

PubMed1997

[Permanent percutaneous electric connection. General principles].

The Swedes for more than twenty years, and the Germans for over five years have been able to maintain inert or active prostheses with permanent percutaneous connections, thanks to the dependable and proven material and techniques of extraoral implants. The significant improvement extra-oral implants have brought about is not only in a new therapeutic approach to the treatment of important facial defects or transmission deafness; it is also because for some twenty old years now, the few millimeter wide cylinders of Titanium, the < > affixed on the implants, have crossed the cutaneous barrier for extended periods without complications. The percutaneous abutment thus creates a permanent communication between the interior and the exterior of the organism. If the abutment, instead of simply carrying a Maxillo-Facial Prosthesis or an auditive prosthesis, is modified by placing an electric conductor inside it, the simple "percutaneous peg" will turn out to be, in a way, a "percutaneous electric plug". By adapting classic "mechanical" abutments and implants, authors have created a Permanent Percutaneous Electric Connection (PPEC) which has been successfully experimented on rabbits to record EEG. Clinical applications on humans would make it possible either to receive "bio-electrical information" coming from within the organism, or to send electrical energy into the organism. This last application opens vast perspectives of improvement both in diagnosis and therapy in many fields.

Humans↗

PubMed1996

Effects of midline and lateral cerebellar lesions on motor coordination and spatial orientation.

Rats were lesioned in the midline cerebellum, comprising the vermis and fastigial nucleus, or the lateral cerebellum, comprising the cerebellar hemispheres and dentate nucleus, and evaluated in a series of motor and non-motor learning tests. Rats with midline lesions had difficulty in maintaining their equilibrium on a bridge and were slower before turning upward and traversed less squares on an inclined grid. They were not impaired for muscle strength when suspended from a horizontal wire. Rats with lateral lesions had milder deficits on the bridge and were not affected in the other two tests. In the Morris water maze test, rats with lateral lesions were deficient in spatial orientation, whereas rats with midline lesions were deficient in visuomotor coordination. Lateral lesions had no effects on visual discrimination learning. These results illustrate the differential influence of midline as opposed to lateral cerebellar regions on both motor and non-motor behaviors. Fastigial nucleus lesions decreased the time spent in equilibrium and latencies before falling on the bridge and the distance travelled along the inclined grid but had no effect on muscle strength when suspended from the horizontal string. Quadrant entries and escape latencies were higher in rats with fastigial lesions during the hidden platform condition of the Morris water maze but not during the visible platform condition. It is concluded that fastigial-lesioned rats are impaired in equilibrium and spatial orientation but with repeated trials learn to improve their performances.

Analysis of Variance↗

PubMed1995

Motor behavior of heterozygous staggerer mutant (+/sg) versus normal (+/+) mice during aging.

Three- to 24-month-old heterozygous staggerer (+/sg) and control (+/+) C57B16 mice were subjected to a motor test on a rota rod rotating at 30 or 40 revolutions per minute. The scores were evaluated by the time during which they maintained their equilibrium without falling down. Although the scores of both +/sg and +/+ animals decreased with age, the scores of +/sg mice were constantly lower at 3, 6 and 12 months and this difference was already significant at 3 months, i.e., before the 30% loss of Purkinje cells, granule cells and inferior olivary neurons which occurs between 3 months and 1 year in the mutant. At 18 months and beyond, scores no longer differed in both groups. These results show that there is no strict correlation between neuronal death in the cerebellar cortex and motor behavior on the rota rod. However, the difficulties in maintaining their equilibrium on the rota rod observed in +/sg mice as young as 3 months, indicate a deficit in accurate motor control which could be due to subtle structural or neurochemical disorders that probably precede neuronal death. Therefore, in the heterozygous staggerer, behavioral motor disturbance is a sign of cerebellar dysfunction which appears earlier than alterations in neuronal number.

Aging↗

PubMed1995

Effects of lesion of the inferior olivary complex in learning of the equilibrium behavior in the young rat during ontogenesis. I. Total lesion of the inferior olive by 3-acetylpyridine.

Young DA/HAN strain rats were submitted to an equilibrium test consisting in maintaining equilibrium upon a rotorod rotating at 10 or 20 rpm. They were either intact or lesioned, the lesion consisting in destruction of the inferior olivary complex (IOC) by 50-95 mg/kg i.p. administration of 3-acetylpyridine (3-AP) at day 15, followed, 2 to 4 h later, by i.p. injection of niacinamide (300 mg/kg). All the 3-AP-treated animals included in this study were completely lesioned, the extent of the lesion being estimated by both the response of the rats to harmaline and histological controls at the end of the experiments. The IOC lesioned rats were either naive (tested at one given day) or trained every day (10 trials per day); among the latters, some were trained before and after the lesion, the others being trained either before or only after. Control rats were submitted to the same training schedule. Both quantitative (time during which the animals maintained the equilibrium upon the rotating rod) and behavioral data (strategy used by the animals to maintain equilibrium) were obtained. The results demonstrate that, compared to those of controls rats, the quantitative and behavioral scores of the IOC lesioned animals were altered. Comparison of naive and trained animals shows that the impairment of the equilibrium behavior is not only due to the ataxia provoked by the IOC lesion but is also due to cognitive deficits. However, prelesion training facilitates the acquisition of a more efficient postlesion equilibrium behavior. From these results, it can be concluded that the olivo-cerebellar pathway is involved in the adaptation of motor behavior to the environmental conditions.

Aging↗

PubMed1995

Differential roles of cerebellar cortex and deep cerebellar nuclei in the learning of the equilibrium behavior: studies in intact and cerebellectomized lurcher mutant mice.

Three- to 6-month-old lurcher mutant mice (+/lc), which exhibit a massive loss of neurons in the cerebellar cortex and in the inferior olivary nucleus but whose deep cerebellar nuclei are essentially intact, were trained daily, for 9 days, to maintain their equilibrium upon a rota rod rotating at 20 or 30 revolutions per minute (rpm). Their scores were measured and their behavior upon the rotating rod quantified in comparison to those of matched control (+/+) mice. Lurcher mice were able to learn to maintain their equilibrium efficiently when rotated at 20 rpm but were not when rotated at 30 rpm. After cerebellectomy, the equilibrium capabilities of the animals were much altered, especially in +/lc. These results show that the deep cerebellar nuclei are sufficient for motor learning, provided the task is not too difficult (20 rpm), but that the cerebellar cortex is required when the task is more difficult (30 rpm). Therefore, it can be concluded that the adaptive motor capabilities of lurcher mice are less developed than those of control animals.

Animals↗

PubMed1995

Role of preoperative and postoperative sensorimotor training on restoration of the equilibrium behavior in adult mice following cerebellectomy.

The equilibrium behavior of cerebellectomized C57/BL6 adult mice was studied on a rota rod rotating at 20 revolutions per minute and the influence of preoperative or/and postoperative training on restoration of equilibrium capabilities investigated. The duration of the preoperative training was either short (1 day) or long (7 days). The postoperative training began either the day after cerebellectomy or was delayed by 7 days. The results demonstrate that postoperative training was efficient in restoring the equilibrium behavior in all cases, except for the animals which were trained for a long period (7 days) before the lesion. Preoperative training was also efficient providing it was long enough (7 days), except for the animals which postoperative training began the day after cerebellectomy. It can be stated that both preoperative and postoperative trainings influence the restoration of the equilibrium following a cerebellectomy and that, in some instances, preoperative training can be as efficient as postoperative.

Animals↗

PubMed1995

Vestibular compensation in the European green frog (Rana esculenta L.) and effect of training on compensation.

Compensation of the vestibular deficits following section of the ampullary nerve of a horizontal semicircular canal was studied from a behavioral point of view in the European green frog. Post-rotation reactions, which are highly asymmetrical the day after the lesion, become symmetrical, as they are in intact animals, 45-60 days later. It was shown that vestibular and motor training given postoperatively did not enhance the rate at which compensation was achieved.

Afferent Pathways↗

PubMed1994

Effect of administration of 3-acetylpyridine followed by niacinamide injection on survival, extent of the inferior olivary complex lesion, and response to harmaline in the young rat.

In the 15 day-old DA/HAN strained rat, i.p. injection of 3-acetylpyridine (3-AP) 50, 65 or 95 mg.kg-1 was followed 2 to 4 hours later by administration of niacinamide (300 mg.kg-1). The percentage of survival and the extent of the inferior olivary complex (IOC) lesion, determined histologically, were correlated with both the dose of 3-AP administered and the time delay between 3-AP and niacinamide injections. Moreover, the tremor elicited by harmaline was also correlated with the extent of the IOC lesion. The results show that it is more advantageous to administer 95 mg.kg-1 3-AP and to delay niacinamide injection by 2h30 or less to get the higher percentage of survival (about 90%) and a reasonably high percentage of totally IOC lesioned rats (more than 30%). They also demonstrate that the harmaline test is not sufficient to acutely judge of the extent of the IOC lesion and that, in all cases, histological controls have to be done. The results are discussed in terms of interrelationships of the variable studied.

Animals↗

PubMed1994

Effects of inhibition of the GABAergic systems by picrotoxin on retention of a nociceptive experience in the rat, with special reference to the influence of cerebellar cortex output.

Adult cerebellectomized and noncerebellectomized DA/HAN strain (pigmented) female rats were submitted to a one-trial passive avoidance conditioning procedure consisting in associating darkness with a nociceptive stimulus. Seven days later, they were tested again to assess the retention stage. The results demonstrate that in noncerebellectomized rats, picrotoxin, whatever the dose, administered prior to the retention test, does not significantly impair retrieval. On the contrary, when administered just prior to the initial conditioning, impairments of the initial single nociceptive experience were evident (the greater the picrotoxin dose, the greater the impairments). In animals that were cerebellectomized 1 week before the experiment, picrotoxin administered at a low dose before the initial experience elicited memory impairments that were similar to those induced in noncerebellectomized rats but that were greater than those elicited in cerebellectomized, nontreated animals. However, in cerebellectomized rats, picrotoxin administered at a low dose elicited memory impairments that were weaker than in noncerebellectomized animals injected with a high dose of the drug. Considering that a low dose of picrotoxin administered to cerebellectomized animals had effects that were similar to those of a high dose injected to noncerebellectomized rats, and given that it has previously been demonstrated that a cerebellectomy performed after a single nociceptive experience impairs its memory, it is tempting to suggest that the two different doses of the drug administered to cerebellectomized and noncerebellectomized rats have similar effects on memory. If such an interpretation is valid, the information would have to leave the cerebellar cortex to be stored for long.

Animals↗