Biomedical subjects

R Lalonde

Publications and source records attributed to R Lalonde.

At least 37 records · Page 2Linked to original sources

PubMed2004

Neurobehavioral evaluation of Reln-rl-orl mutant mice and correlations with cytochrome oxidase activity.

The Reln-rl-orl mutation is characterized by a marked deficit in cerebellar granule cell and Purkinje cell number as well as ectopias in cerebellum, hippocampus, and neocortex. By comparison to Balb/c controls, Reln-rl-orl mutants did not alternate spontaneously in a T-maze and were deficient for visuomotor guidance in a water maze. Despite cerebellar ataxia and motor coordination impairments on stationary beam, coat-hanger, and rotorod tests, the horizontal motor activity of Reln-rl-orl mutants was not reduced in an open-field. The elevated cytochrome oxidase (CO) activity in Purkinje cells and the reduced CO activity in the roof nuclei (interpositus and dentate) of the mutants were associated with poor performance on the small stationary beam. In addition, deficient CO activity of the granular layer of the motor cortex was associated with shorter latencies before falling from the larger stationary beam and a lower number of rears in the open-field. Conversely, elevated CO activity in the polymorphic layer of primary somatosensory cortex was congruent with higher latencies before falling from the same apparatus, indicating functional compensation.

Animals↗

PubMed2003

Transgenic mice expressing the betaAPP695SWE mutation: effects on exploratory activity, anxiety, and motor coordination.

The functional consequences of the betaAPP transgene with the Swedish mutation in mice were assessed in tests of exploratory activity and motor coordination. The betaAPP(695)SWE (Tg2576) transgenic mice are characterized by Abeta plaque formation in the neocortex and hippocampus. By comparison to non-transgenic mice controlled for age and gender, 17-month-old betaAPP(695)SWE transgenic mice displayed impaired spontaneous alternation, increased activity levels in the peripheral part of the open-field, and reduced anxiety in the elevated plus-maze. These results are similar to the loss of inhibitory control observed in some patients with Alzheimer's disease. These measures may be added to cognitive dysfunctions as testing ground for Abeta vaccination and other attempts at experimental therapies.

Alzheimer Disease↗

PubMed2003

Characterization of NFH-LacZ transgenic mice with the SHIRPA primary screening battery and tests of motor coordination, exploratory activity, and spatial learning.

NFH-LacZ transgenic mice express a fusion protein between a truncated form of the endogenous neurofilament of heavy molecular weight and the complete E. coli beta-galactosidase. NFH-LacZ transgenic mice could be distinguished from controls in the SHIRPA neurological battery by the appearance of action tremor and hindlimb clasping and a lower body weight. Despite normal exploratory activity and spatial learning, NFH-LacZ transgenic mice were deficient in stationary beam, coat-hanger, and rotorod tests of motor coordination. These results are concordant with neuropathological findings in spinal motoneurons and the cerebellum and indicate that despite the absence of paralysis, these transgenic mice may serve as an experimental model of the early stage of amyotrophic lateral sclerosis.

Journal Article↗

PubMed2003

Transgenic mice expressing the PS1-A246E mutation: effects on spatial learning, exploration, anxiety, and motor coordination.

The functional consequence of the PS1-A246E mutation was assessed in transgenic mice on a background lacking the endogenous PS1 gene. These mice have elevated concentrations of A-beta protein (Abeta(42)) in the absence of plaque formation. By comparison to a mixed background strain (50% B6, 25% SJl, 25% 129Sv) controlled for age and gender, PS1-A246E transgenic mice displayed disinhibitory tendencies, as indicated by increased entries and duration in the open arms of the elevated plus-maze. Despite normal spontaneous alternation rates in a T-maze, latencies before responding were higher in PS1-A246E transgenic mice than controls. Moreover, the PS1-A246E transgenic mice fell more often from two stationary beams, but not from the coat-hanger and the rotorod. By contrast, ambulation in an automated photocell chamber and in an open-field was not affected. Nor was acquisition of place learning in the Morris water maze task. These results indicate that elevated Abeta(42) levels were insufficient for causing spatial defects but caused disinhibition, psychomotor slowing, and loss of motor skills in this model of familial Alzheimer's disease.

Alzheimer Disease↗

PubMed2003

Changes in immunological and virological parameters in HIV-1 infected subjects following leukapheresis.

In order to assess immune responses during HIV-1 therapeutic immunization, a large number of blood mononuclear cells (PBMC) are needed. Clinical tolerance and safety, as well as changes in immunological and virological parameters, were assessed, following leukapheresis in HIV-1 infected subjects with CD4(+) cell count >200 x 10(6)/l. PBMC were collected using a Fenwal CS3000 cell separator in 29 subjects with mean CD4(+) cell counts of 503 x 10(6)/l (range 172-1,119) and viral load of 2.5 log(10) copies/ml (range <1.7-5.4). Twenty-four (83%) subjects were on antiretroviral therapy while 5 (17%) were untreated. The blood volume processed was 7 L over a period of 3 hours. A mean value (+/- standard error) of 82 +/- 26 x 10(9)/l lymphocytes was collected by a single apheresis in a mean volume of 200 +/- 1.8 ml, containing 9.0 +/- 1.3 x 10(9)/l CD4(+) and 10.2 +/- 1.3 x 10(9)/l CD8(+) cells. The leukapheresis procedures were well tolerated and no immediate or delayed side effects were observed within 90 days of follow-up. No changes from blood pre-leukapheresis values were detected for white blood cells, lymphocytes, monocytes, CD8(+), CD34(+), naive and memory CD4(+) cell counts immediately after, 1 h, 7 days, or within 90 days after leukapheresis. However, absolute CD4(+) cell counts and percentage significantly increased from pre-leukapheresis values after 1 h (530 +/- 43 vs. 700 +/- 75 cell x 10(6)/l; 32.6 +/- 1.6 vs. 36.9 +/- 1.9%; P < 0.001 for both paired t-tests) before returning to pre-leukapheresis levels on day 7. No significant changes in viral load from pre-leukapheresis levels in treated or untreated subjects were detected at any time points. We conclude that leukapheresis in HIV-1 infected subjects with CD4(+) cell counts >200 x 10(6)/l is safe and induces a transient increase in the absolute and percentage of CD4(+) cell count without enhancing viral replication.

Adult↗

PubMed2003

Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor.

Grid2(ho/ho) is a loss of function gene mutation resulting in abnormal dendritic arborizations of Purkinje cells. These mutants were compared in a series of motor coordination tests requiring balance and equilibrium to nonataxic controls (Grid2(ho/+)) and to a double mutant (Grid2(ho/Lc)) with an inserted Lc mutation. The performance of Grid2(ho/ho) mutant mice was poorer than that of controls on stationary beam, coat hanger, unsteady platform, and rotorod tests. Grid2(ho/Lc) did not differ from Grid2(Lc/+) mice. However, the insertion of the Lc mutation in Grid2(ho/Lc) potentiated the deficits found in Grid2(ho/ho) in stationary beam, unsteady platform, and rotorod tests. These results indicate a deleterious effect of the Lc mutation on Grid2-deficient mice.

Alleles↗

PubMed2003

Effects of ventrolateral-ventromedial thalamic lesions on motor coordination and spatial orientation in rats.

The ventrolateral-ventromedial (VL-VM) nuclei are classified as a motor area of the thalamus on the basis of predominant input from the cerebellum and the basal ganglia and output to the motor cortex. The sensitivity to electrolytic lesions of the VL-VM thalamic nuclei in rats was evaluated for tests requiring balance and equilibrium. VL-VM lesions impaired acquisition of the rotorod test but had no effect on stationary beam and hole-board tests. A selective impairment was also observed in the Morris water maze, as VL-VM thalamic lesions slowed down acquisition of the hidden platform but not the visible platform condition. These results support the hypothesis that thalamic motor nuclei participate in the acquisition of sensorimotor and spatial learning.

Animals↗

PubMed2003

Regional brain cytochrome oxidase activity in beta-amyloid precursor protein transgenic mice with the Swedish mutation.

Cytochrome oxidase activity was examined in a transgenic mouse model of Alzheimer's disease with overexpression of the 751 amino acid isoform of beta-amyloid precursor protein with the Swedish mutation under control of the murine thy-1 promoter. The neuritic plaques, abundantly localized in the hippocampus and anterior neocortical areas, showed a core devoid of enzymatic activity surrounded by higher cytochrome oxidase activity at the sites of the dystrophic neurites and activated glial cells. Quantitative measures, taken only in the healthy-appearing regional areas without neuritic plaques, were higher in numerous limbic and non-limbic regions of transgenic mice in comparison with controls. Enzymatic activity was higher in the dentate gyrus and CA2-CA3 region of the hippocampus, the anterior cingulate and primary visual cortex, two olfactory structures, the ventral part of the neostriatum, the parafascicularis nucleus of the thalamus, and the subthalamic nucleus. Brainstem regions anatomically related with altered forebrain regions were more heavily labeled as well, including the substantia nigra, the periaqueductal gray, the superior colliculus, the medial raphe, the locus coeruleus and the adjacent parabrachial nucleus, as well as the pontine nuclei, red nucleus, and trigeminal motor nucleus. Functional brain organization is discussed in the context of Alzheimer's disease. Although hypometabolism is generally observed in this pathology, the increased cytochrome oxidase activity obtained in these transgenic mice can be the result of a functional compensation on the surviving neurons, or of an early mitochondrial alteration related to increased oxidative damage.

Alzheimer Disease↗

PubMed2003

Motor coordination, exploration, and spatial learning in a natural mouse mutation (nervous) with Purkinje cell degeneration.

The nervous mouse mutation causes a relatively selective degeneration of Purkinje cells in the cerebellar cortex. The mutants were compared to age-matched controls of the same background strain in tests of motor activity and coordination, spontaneous alternation, and spatial learning in the Morris water maze. As expected from their ataxia, the nervous mutants were impaired in stationary beam, coat-hanger, and rotorod tests of motor coordination. The nervous mutants were also impaired in the submerged but not in the visible platform condition of the Morris water maze, attributable to a spatial deficit, and displayed a higher level of motor activity in an automated chamber. The deficit in spontaneous alternation rates seen in nervous mutants is accountable by reduced motivation, disinhibition, or spatial disorientation.

Analysis of Variance↗

PubMed2003

The effects of cerebellar damage on maze learning in animals.

The role of the cerebellum in spatial learning has recently been investigated in genetically and non-genetically lesioned animal models, particularly in water mazes, in view of the minimal impact such lesions exert on swimming movements. A dissociation between place and cued learning in the Morris water maze has been observed in several models, including cerebellar mutant mice (Rora(sg), Nna1(pcd-1J), nervous), rats with lesions of either the lateral cerebellar cortex or the dentate nucleus, and rats with selective Purkinje cell loss caused by intracerebroventricular injections of OX-7-saporin, confirming the hypothesis that cerebellar damage may cause a cognitive deficit independently of fine motor control. In addition, the results of hemicerebellectomized rats indicate the probable involvement of the cerebellum in working memory and the procedural aspect of maze learning. The findings of impaired maze learning in cerebellar-lesioned mice and rats are concordant with those of deficient visuospatial functions in patients with cerebellar atrophy. The spatial deficits may be ascribed to altered metabolic activity in cerebellar-related pathways.

Animals↗

PubMed2003

Neurobehavioral characteristics of mice with modified intermediate filament genes.

Intermediate proteins comprise cytoskeletal elements that preserve the shape and structure of neurons. These proteins have been proposed to be involved in the onset and progression of amyotrophic lateral sclerosis (ALS), mainly characterized by motoneuron atrophy and paresis. In support of this hypothesis are the findings that genetically modified mice for intermediate filaments successfully mimic certain neuropathological aspects of ALS, such as reduced axonal caliber and retarded conduction speed in peripheral nerves, although often without leading to paresis. Nevertheless, even in those models with no overt phenotype, the involvement of intermediate proteins in motor function is underlined by the deficits in tests of balance and equilibrium revealed in mice containing transgenes for neurofilament of heavy molecular weight (NFH), alpha-internexin, peripherin, and vimentin. In addition, spatial learning was impaired in transgenic mice expressing transgenes for NFH and NFM, similar to the memory deficits reported in patients with ALS.

Amyotrophic Lateral Sclerosis↗

PubMed2002

Spatial learning, exploration, anxiety, and motor coordination in female APP23 transgenic mice with the Swedish mutation.

Transgenic mice overexpressing the betaAPP gene with the Swedish mutation under the control of the murine thy-1 promoter show Alzheimer-like characteristics including the accumulation of Abeta protein in the cerebral cortex. Female 16-month-old APP23 transgenic mice were compared to age-matched non-transgenic mice in behavioral tests measuring spatial learning, exploration of environmental stimuli, anxiety, and motor coordination. APP23 transgenic mice had fewer fast ambulatory movements, either fast or slow stereotypy movements, and slow rears in a photocell activity chamber. The acquisition of spatial learning in the Morris water maze was impaired in APP23 transgenic mice, but not during the probe test or while swimming towards a visible platform. Neither were there intergroup differences in tests of anxiety or motor coordination. These results indicate that a learning deficit and hypoactivity, concordant with the early stages of Alzheimer's disease, characterize this mouse model with Abeta accumulation.

Alzheimer Disease↗

PubMed2002

The effects of unilateral removal of the cerebellar hemispheres on motor functions and weight gain in rats.

Left or right unilateral removal of a cerebellar hemisphere resulted in a high mortality rate caused by anorexia, not previously seen in cerebellectomized animals. The reduced post-surgical gain in body weight may be explained by oropharyngeal dyspraxia or a loss in appetite. However, the growth rate of the surviving animals was similar to that of controls. After unilateral damage of the cerebellum, deficits were observed in motor coordination tasks, such as the rotorod, the hole-board, and the stationary beam, and the left hemisphere group fell from a suspended wire sooner than controls. The motor deficits were more pronounced after left as opposed to right cerebellar damage on the rotorod, implying a certain degree of functional lateralization for this test.

Animals↗

PubMed2002

NFH-LacZ transgenic mice: regional brain activity of cytochrome oxidase.

Expression of the NFH-LacZ fusion protein in transgenic mice causes an early accumulation of neurofilament proteins in the cell bodies of neurons, as well as a reduction of motor neuron axonal caliber and Purkinje cell number in the cerebellum. Young (3 month old) and older (12-20 months) NFH-LacZ transgenic mice were compared to normal controls for regional brain metabolism, as assessed by cytochrome oxidase (CO) activity. Irrespective of age, CO activity was reduced in three cerebellar-related regions of NFH-LacZ transgenic mice: (1) the lateral reticular nucleus, (2) the parvicellular red nucleus, and (3) the superior colliculus, possibly as a secondary consequence of cerebellar Purkinje cell histopathology. Aged NFH-LacZ mice had lower CO activity relative to either age-matched controls or young transgenic mice in the following regions: the motor nucleus of the vagus nerve, the trapezoid nucleus, the subiculum, the motor cortex, the superior olive, and the lateral dorsal thalamus. These results indicate regional and age-selective deficits of brain metabolism in a transgenic model with neurofilament maldistribution.

Age Factors↗

PubMed2002

Exploration and motor activity in juvenile and adult rats exposed to hypergravity at 1.8 G during development: a preliminary report.

Pups from gestating rats exposed to hypergravity (1.8 G) or to normal gravity at the perinatal period were evaluated for motor activity, exploration and social interactions during juvenile and adult stages. By comparison to controls, the hypergravity group had shorter latencies before choosing a maze arm in a T-maze and a lower number of exploratory pokes in a hole board. During dyadic encounters, the hypergravity group had a lower number of self-grooming episodes and shorter latencies before crossing under the opposing rat. In contrast, no intergroup differences were observed during exploration of an elevated plus-maze and a light-dark box. These results indicate that exposure to 1.8 G during development appears to decrease exploratory tendencies in the hole board and fear-related responses in T-maze and social interaction tests.

Aging↗

PubMed2002

Sensorimotor functions in transgenic mice expressing the neurofilament/heavy-LacZ fusion protein on two genetic backgrounds.

NFH-LacZ transgenic mice are characterized by expression of a non-endogenous fusion protein between a truncated form of mouse NFH (neurofilament of heavy molecular weight) and the complete Escherichia coli beta-galactosidase protein. These transgenic mice were compared to their respective controls on two background strains (C3H and FVB) in several sensorimotor tests. NFH-LacZ mice were deficient in tests requiring balance and equilibrium in a manner generally independent of genetic background. In particular, NFH-LacZ mice fell more quickly than controls from two stationary beams and had fewer rears in an open-field. The transgenic mice were also impaired during the initial trials of sensorimotor learning on the rotorod. We conclude that despite the absence of overt signs of sensorimotor weakness in their home cage, the disruption of the NFH gene, causing neurofilament accumulations in the cell body and diminished axonal calibers of motoneurons, is sufficient to cause motor deficits that resemble the early stages of amyotrophic lateral sclerosis.

Animals↗

PubMed2002

Comparisons between C57BL/6J and A/J mice in motor activity and coordination, hole-poking, and spatial learning.

The C57BL/6J (B6) inbred mouse strain was compared to the A/J inbred strain for motor activity in an open-field, exploration of a hole-board, motor coordination in the coat-hanger test, and spatial learning in the Morris water maze. B6 mice displayed a higher number of segment crossings in the open-field and of hole-poking responses than A/J mice. The performance of B6 mice was superior to that of A/J mice not only in the submerged but also in the visible platform version of the Morris water maze. By contrast to their hypoactivity, the A/J strain had shorter movement times in the coat-hanger test, indicating faster motor speed, although the groups did not differ in latencies before falling. These results indicate that recombinant inbred or congenic strains derived from B6 and A/J mice offer considerable potential for discerning the genetic basis of several behavioral phenotypes.

Animals↗

PubMed2002

Transgenic mice expressing the human C99 terminal fragment of betaAPP: effects on spatial learning, exploration, anxiety, and motor coordination.

The functional consequence of beta-amyloid precursor protein (betaAPP) manipulation on behavior was assessed in Tg13592 mice, characterized by transgene expression of the 99 amino acid C-terminal sequence of human betaAPP in brain and skeletal muscle but with plaque formation only in muscle. By comparison to the C57BL/6 background strain controlled for age and gender, Tg13592 transgenic mice had fewer movements in an automated chamber and fewer enclosed arm entries in the elevated plus-maze. This hypoactivity was probably due to a loss in the motivation to explore novel environmental stimuli rather than motor weakness or anxiety. In addition, the acquisition of place learning in the Morris water maze task was impaired in Tg13592 mice. The transgenic mice were not impaired in a probe trial or while swimming toward a visible platform. These results are concordant with the hypothesis that transgene expression of the C-terminal sequence of human betaAPP in brain is sufficient for causing behavioral abnormalities. The hypoactivity and the spatial learning deficit were associated with higher cytochrome oxidase activity seen in thalamic nuclei, indicating that altered regional brain metabolism caused by betaAPP transgene expression may be responsible for the behavioral changes.

Amyloid beta-Protein Precursor↗