Biomedical subjects

Jacques Durand

Publications and source records attributed to Jacques Durand.

4 recordsLinked to original sources

PubMed2006

Early abnormalities in transgenic mouse models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative and fatal human disorder characterized by progressive loss of motor neurons. Transgenic mouse models of ALS are very useful to study the initial mechanisms underlying this neurodegenerative disease. We will focus here on the earlier abnormalities observed in superoxide dismutase 1 (SOD1) mutant mice. Several hypotheses have been advanced to explain the selective loss of motor neurons such as apoptosis, neurofilament disorganisation, oxidative stress, mitochondrial dysfunction, astrogliosis and excitotoxicity. Although disease onset appears at adulthood, recent studies have detected abnormalities during embryonic and postnatal maturation in animal models of ALS. We reported that SOD1(G85R) mutant mice exhibit specific delays in acquiring sensory-motor skills during the first week after birth. In addition, physiological measurements on in vitro spinal cord preparations reveal defects in evoking rhythmic activity with N-methyl-DL-aspartate and serotonin at lumbar, but not sacral roots. This is potentially significant, as functions involving sacral roots are spared at late stages of the disease. Moreover, electrical properties of SOD1 lumbar motoneurons are altered as early as the second postnatal week when mice begin to walk. Alterations concern the input resistance and the gain of SOD1 motoneurons which are lower than in control motoneurons. Whether or not the early changes in discharge firing are responsible for the uncoupling between motor axon terminals and muscles is still an open question. A link between these early electrical abnormalities and the late degeneration of motoneurons is proposed in this short review. Our data suggest that ALS, as other neurodegenerative diseases, could be a consequence of an abnormal development of neurons and network properties. We hypothesize that the SOD1 mutation could induce early changes during the period of maturation of motor systems and that compensatory mechanisms-linked to developmental spinal plasticity-might explain the late onset of the disease.

Amyotrophic Lateral Sclerosis↗

PubMed2004

Altered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosis.

Most neurodegenerative diseases become manifest at an adult age but abnormalities or pathological symptoms appear earlier. It is important to identify the initial mechanisms underlying such progressive neurodegenerative disease in both humans and animals. Transgenic mice expressing the familial amyotrophic lateral sclerosis (ALS)-linked mutation (G85R) in the enzyme superoxide dismutase 1 (SOD1) develop motor neuron disease at 8-10 months of age. We address the question of whether the mutation has an early impact on spinal motor networks in postnatal mutant mice. Behavioural tests showed a significant delay in righting and hind-paw grasping responses in mutant SOD1G85R mice during the first postnatal week, suggesting a transient motor deficit compared to wild-type mice. In addition, extracellular recordings from spinal ventral roots in an in vitro brainstem-spinal cord preparation demonstrated different pharmacologically induced motor activities between the two strains. Rhythmic motor activity was difficult to evoke with N-methyl-DL-aspartate and serotonin at the lumbar levels in SOD1G85R mice. In contrast to lumbar segments, rhythmic activity was similar in the sacral roots from the two strains. These results strongly support the fact that the G85R mutation may have altered lumbar spinal motor systems much earlier than previously recognized.

Action Potentials↗

PubMed2002

Rapid effects of glucose on the insulin signaling of endothelial NO generation and epithelial Na transport.

Insulin resistance is associated with deficits in glucose metabolism. We tested whether the vascular and renal responses to insulin might contribute to insulin resistance. Generation of endothelial-derived vasodilator nitric oxide (NO), estimated after a 2-h period of insulin stimulation, was inhibited in the presence of high glucose. Immunoprecipitations indicated that insulin-induced endothelial signal transduction was mediated through an immediate complex formation of insulin receptor substrate (IRS) with phosphatidylinositol 3-kinase, which caused serine phosphorylation of a protein complex that was comprised of Akt kinase and endothelial NO synthase. The enzymatic complexes did not form when the endothelial insulin stimulation occurred in the presence of high glucose concentrations. By contrast, neither epithelial signal transduction nor sodium transport in renal epithelial cells was affected by high glucose. Hence, glucose does not appear to modulate either the epithelial IRS cascade or renal sodium retention. Dysfunction of the endothelial IRS cascade and NO generation, which suppresses efficient delivery of nutrients, may further exacerbate the metabolic syndrome of insulin resistance.

Biological Transport↗

PubMed1991

NMDA Actions on Rat Abducens Motoneurons.

Intracellular recordings were made from rat abducens motoneurons in vivo during local extracellular micro-ionophoretic application of N-methyl-d-aspartate (NMDA) and NMDA receptor antagonists. Typical NMDA responses, at a resting potential of -60 mV, consisted of a slow depolarization with an apparent increase in membrane resistance, bursts of action potentials followed by stable repetitive firing. Ionophoretic applications of aminophosphonovalerate (APV), kynurenate or MK801 reduced or blocked the NMDA-induced responses. The NMDA responses were voltage-dependent. NMDA responses induced by short (< 30 s) NMDA application pulses were blocked by hyperpolarizing the neuron. Long duration (> 30 s) NMDA applications induced rhythmic plateau potentials in hyperpolarized abducens motoneurons. The rhythmic depolarizations (15 - 30 mV) were modulated in both frequency and duration by current injection. They were abolished by further hyperpolarization or replaced by stable repetitive firing when hyperpolarization was removed. Our data show that NMDA receptors are present in rat abducens motoneurons and may be involved in the induction of rhythmic activities. The voltage-dependent blockade of somatic NMDA receptor-associated ion channels by cell hyperpolarization may be important for these oscillations. It is suggested that the rhythmic behaviour is due to the activation of dendritic NMDA receptors.

Journal Article↗