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Biomedical subjects

R Lalonde

Publications and source records attributed to R Lalonde.

At least 127 records · Page 7Linked to original sources

Motor learning in lurcher mutant mice.

Lurcher mutant mice, characterized by degeneration of the olivo-cerebellar system, were evaluated in two tests of motor coordination: the inclined screen test and the tilted platform test. Lurcher mutants were not impaired, in comparison to normal littermate controls, in the inclined screen test. In the tilted platform test, lurcher mutants fell more quickly than normal mice. However, with repeated testing, the amount of time spent on the platform by lurcher mutants and controls increased at the same rate within a 3 day period. These results demonstrate that lurcher mutants, although ataxic, have spared motor capabilities. In a test where motor deficits occurred, rapid improvement was seen. Thus, in spite of massive cerebellar degeneration, there was no evidence of a decreased rate in motor learning.

Animals↗

Absence of an association between motor coordination and spatial orientation in lurcher mutant mice.

Lurcher mutant mice were impaired in spatial orientation and motor coordination in comparison to normal mice. Both groups improved across days in both invisible and visible water maze platform conditions. Contrary to normal mice, lurcher mutants did not improve over days in terms of the time taken to reach a side-bar in a motor coordination test, an indication of defective motor learning. However, lurchers were able to stay on the bar longer across days. These results indicate that motor learning deficits in this cerebellar-damaged animal are not absolute but dependent on the type of measurement attempted. There was no correlation between motor coordination and spatial orientation for normal mice. A similar absence of correlation was noted for lurcher mutants, except for falling latencies in the coat-hanger test during the middle of training.

Animals↗

Exploration and motor coordination in dystonia musculorum mutant mice.

Dystonia musculorum (dt) mutant mice, characterized by degeneration of spinocerebellar tracts, were impaired in terms of horizontal and vertical motor activity, hole poking, exploration, and motor coordination. In tests of motor coordination, their deficits were more severe than those of previously tested mutant mice with degeneration of cerebellar cells. However, unlike other cerebellar mutants, dt mutants alternated above chance levels in a two-trial spontaneous alternation test, which is a test of inhibitory tendencies and spatial orientation, and so dt mutants may not be impaired in these functions.

Animals↗

Effects of an ectodermal microceptor preparation on motor coordination in cerebellar mutant mice.

Lurcher mutant mice, characterized by degeneration of the olivocerebellar system, and dystonia musculorum (dt) mutant mice, characterized by degeneration of spinocerebellar fibers, were treated with an ectodermal microceptor preparation (EMP), a compound containing natural substances derived from embryonic bovine ectodermal tissue, or with placebo, and evaluated in motor coordination tests. EMP-treated lurchers, but not dt mutants, were quicker to initiate movement than placebo-treated controls in the inclined beam test. No group differences were found in terms of distance travelled on the beam or in motor coordination assessed in a more challenging coat-hanger test. These results indicate that ectodermal microceptors may improve movement initiation of cerebellar-related disorders in animals, but that these effects are test and disease-specific.

Animals↗

Cerebellar contributions to instrumental learning.

There is emerging evidence that the cerebellum is involved in spatial and nonspatial instrumental learning tasks. Cerebellar-lesioned animals have deficits in water maze learning tasks that may be explained by two-way interactions with higher order brain regions. There is suggestive evidence that cerebellar modulation extends to shock avoidance and discrimination learning. Although this evidence needs to be confirmed by a wider range of lesion methods and choice of learning tasks, it is in line with the hypothesis that the cerebellum affects cognitive processes and is not strictly concerned with motor control and the acquisition and retention of conditioned reflexes.

Animals↗

Inhibitory effect of 3'-azido-3'-deoxythymidine on proliferative responsiveness of CD8+ lymphocytes to interleukin-2.

Although several studies have shown that 3'-azido-3'-deoxythymidine (AZT) is not toxic for CD4+ lymphocytes, its effect on CD8+ cells has never been studied in a systematic way. We purified CD8+ cells from the peripheral blood mononuclear cells of both human immunodeficiency virus (HIV)-seronegative and HIV-infected individuals by means of magnetic beads that had been coated with monoclonal antibodies. We report that AZT, but not two other nucleosides tested, inhibited the interleukin-2-dependent proliferation of CD8+ lymphocytes in a dose-dependent manner. No such effect was observed with regard to CD4(+)-enriched populations. The AZT-mediated antiproliferative effect did not appear to be related to either the CD4+ count or to prior treatment with this drug in the case of HIV-seropositive subjects.

Antiviral Agents↗

Expression of human immunodeficiency virus type 1 in the nervous system of transgenic mice leads to neurological disease.

Patients infected with the human immunodeficiency virus type 1 (HIV-1) frequently develop central and peripheral nervous system complications, some of which may reflect the effect of the virus itself. In order to elucidate the pathogenic mechanisms of HIV in neurological disease in a small animal model, we generated transgenic mice expressing the entire HIV genome under control of the promoter for the human neurofilament NF-L gene. The transgene was predominantly expressed in anterior thalamic and spinal motor neurons. Animals developed a neurological syndrome characterized by hypoactivity and weakness and by axonal degeneration in peripheral nerves. These results provide evidence for a role of HIV in affecting both the central and peripheral nervous systems. This animal model may also facilitate the development of therapeutic agents against the human disease.

Animals↗

[Psychoimmunology and AIDS: a review of the literature].

In recent years, several studies have been carried out concerning the effect of psychosocial factors on the course of infection due to the human immunodeficiency virus (HIV). After summarizing the current status of general knowledge in the field of psychoimmunology, this article reviews the results of studies conducted in regard to HIV. Two conclusions are reached. The first is that current research has not shown psychosocial factors to have any impact on either the immunity status of seropositive patients or the medical complications inherent to AIDS. The second conclusion is that several types of intervention, in particular psychoeducational approaches, stress management programs, and the strengthening of social and family support, give good results where the psychosocial well-being of patients is concerned and should motivate various health professionals to improve the focus of their interventions. Furthermore, significant methodological weaknesses in several indexed studies are noted, and these should be rectified to enable future studies to confirm or correct the present observations.

Acquired Immunodeficiency Syndrome↗

Simultaneous visual discrimination learning in lurcher mutant mice.

Lurcher mutants were evaluated in the acquisition of a visual discrimination learning task with water escape as a reward. In comparison to normal mice, lurchers were impaired in discrimination learning in a manner not explainable by motor deficits. Although in initial trials the mutants had difficulty in finding the correct invisible platform, in agreement with previous findings of deficits in visuo-spatial organization, they eventually were able to find the quadrants where one of two platforms was situated but even so took longer to reach criterion in choosing the correct one. These results agree with the hypothesis that the cerebellum is involved in the acquisition of visual discrimination tasks in mice.

Animals↗

Hole poking and motor coordination in lurcher mutant mice.

Lurcher mutant mice, a cerebellar mutant displaying ataxia and equilibrium deficits, had fewer hole pokes in a 16-hole matrix than normal mice. Lurcher mutants also took longer to reach a platform from a grid and to begin to climb a grid from the floor. However, the lurchers climbed as high as normal mice on the grid and their exploratory patterns of the holeboard were similar in many respects to normal mice, such as the ratio of center to peripheral hole exploration. In a wooden beam test, although lurchers did not differ from normal mice in terms of the amount of time spent on the beam or in the distance travelled, the mutants were found more often in unstable positions.

Animals↗

Swimming activity in dystonia musculorum mutant mice.

Dystonia musculorum (dt) mutant mice, characterized by degeneration of spinocerebellar fibers, were evaluated in a visible platform swim test. It was found that dt mutants were slower to reach the platform than normal mice. However, the number of quadrants traversed was not higher in dt mutants. It is concluded that spinocerebellar fibers to the vermis are important in limb control during swimming but not in visuo-motor guidance (navigational skills) of the animal towards a visible goal, at least in regard to the quadrant measure. It is not excluded that a measure tracing their path may find a mild deviation from the goal.

Animals↗

Effects of ketamine and L-glutamic acid diethyl ester on spatial and nonspatial learning tasks in rats.

An NMDA antagonist, ketamine, at the highest dose tested (15 mg/kg), impaired the acquisition of a hole-board spatial learning task but not the acquisition of a left-right alternation task. A non-NMDA (quisqualate) antagonist, L-glutamic acid diethyl ester (LGDE), did not impair the acquisition of either task. Both drugs had effects on different aspects of a go-no go discrimination task and a straight runway task, ketamine tending to activate and LGDE tending to slow rats. These results concur with previous research regarding the sensitivity of some spatial tasks to NMDA antagonism. Non-NMDA antagonists affect behavior without causing spatial deficits.

Animals↗

Effects of folic acid and folinic acid on cognitive and motor behaviors in 20-month-old rats.

Old rats had lower plasma concentrations of folates but not of vitamin B12 than young rats. Old rats injected with pharmacological doses of folic acid (5 mg/kg) or folinic acid (2.5 mg/kg) every 2 days for a 32-day period spontaneously alternated above chance levels at the 0-min retention interval whereas old rats injected with placebo did not. Rats injected with folinic acid that had plasma folate concentrations above the median for that group alternated at the 3-min retention interval whereas none of the other subgroups did. These results indicate that supplementation with folinic acid at pharmacological doses may decrease perseverative responding and improve spatial memory in old rats. However, neither vitamin group was improved in motor coordination, grip strength, or spatial learning in a water maze. There was no hyperactivity or loss of body weight following vitamin supplementation.

Aging↗

Thiamine and folate treatment of chronic epileptic patients: a controlled study with the Wechsler IQ scale.

Seventy-two epileptic patients receiving phenytoin (PHT) alone or in combination with phenobarbital for more than 4 years were divided into four groups, the first taking two placebo tablets per day; the second folate (5 mg/day) and placebo; the third placebo and thiamine (50 mg/day); and the fourth both vitamins. The clinical trial lasted 6 months. At baseline assessment, 31% of the patients had subnormal blood thiamine levels and 30% had low folate. The vitamin deficiencies were independent phenomena. It was found that thiamine improved neuropsychological functions in both verbal and non-verbal IQ testing. In particular, higher scores were recorded on the block design, digit symbol, similarities and digit span subtests. Folate treatment was ineffective. These results indicate that, in epileptics chronically treated with PHT, thiamine improves neuropsychological functions, such as visuo-spatial analysis, visuo-motor speed and verbal abstracting ability.

Adult↗

Behavioral effects of non-NMDA glutamate receptor antagonists.

Non-NMDA receptor antagonists decrease motor activity in some situations, alter the sleep-wake cycle, possess anticonvulsant and neuroprotectant actions, and appear to impair some learning tasks but not others. NMDA receptor antagonists affect these same functions but often in different and even opposite ways. NMDA receptor antagonists impair many different spatial learning tasks, including the Morris water maze, the Olton radial maze, and the hole-board task. Non-NMDA receptor antagonists are either ineffective in these spatial tasks or have not yet been evaluated. However, non-NMDA receptor antagonists may impair associative processes required in a bar-press response and in discrimination learning. Further research is needed in the context of comparing NMDA as opposed to non-NMDA receptor antagonists within the same paradigm.

Animals↗

Motor abnormalities in lurcher mutant mice.

Lurcher mutants had deficits in equilibrium in the coat-hanger and grid tests but not the wooden beam test. Although the mutants had less hole-pokes when confronted with small holes in most conditions, they had more hole-pokes with larger holes, demonstrating perseverative behavior. There was no decrease in rearing responses. These results indicate that in spite of cerebellar degeneration and ataxia, lurcher mutants are not impaired in all tests measuring motor function.

Animals↗