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Y Lamour

Publications and source records attributed to Y Lamour.

At least 19 recordsLinked to original sources
PubMed1997

Brain-derived neurotrophic factor increases Ca2+/calmodulin-dependent protein kinase 2 activity in hippocampus.

Here we show that brain-derived neurotrophic factor (BDNF) stimulates both the phosphorylation of the Ca2+/calmodulin-dependent protein kinase 2 (CaMK2) and its kinase activity in rat hippocampal slices. In addition, we find that: (i) the time course of BDNF action is not accompanied by a change in the spectrum of either alpha- and beta-subunits of CaMK2 detected by immunoblotting; (ii) both treatment of solubilized CaMK2 with alkaline phosphatase and treatment of immunoprecipitated CaMK2 with protein phosphatase 1 reverse phosphorylation and activation of the kinase; (iii) phospholipase C inhibitor D609 and intracellular Ca2+ chelation by 1,2-bis-(o-aminophenoxy)ethane-N,N,N",N',-tetracetic acid tetra(acetoxymethyl)ester or 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate but not omission of Ca2+ or Ca2+ chelation by EGTA, abolish the stimulatory effect of BDNF on phosphorylation and activation of CaMK2. These results strongly suggest that the conversion of CaMK2 into its active, autophosphorylated form, but not its concentration, is increased by BDNF via stimulation of phospholipase C and subsequent intracellular Ca2+ mobilization.

Animals↗
PubMed1997

Potentiation of glutamatergic EPSPs in rat CA1 hippocampal neurons after selective cholinergic denervation by 192 IgG-saporin.

A complete and selective destruction of the basal forebrain cholinergic neurons projecting to the cerebral cortex and the hippocampus was induced in the rat by the toxin 192 IgG-saporin. Using electrophysiologic techniques, we have investigated the consequences of this cholinergic denervation on inhibitory and excitatory synaptic responses of CA1 pyramidal cells in rat hippocampal slices ex vivo. Histochemical experiments were performed in slices from control and 192 IgG-saporin-treated rats to check the efficacy of the intracerebroventricular injection of the immunotoxin. Stimulation of stratum radiatum elicits a glutamatergic excitatory postsynaptic potentials followed by a biphasic GABAergic inhibitory postsynaptic potential (IPSP). No significant change in IPSP was observed in 192 IgG-saporin-treated rats. By contrast, the N-methyl-D-aspartate (NMDA) and to a lesser extent the non-NMDA components of the glutamatergic response were potentiated in these animals. The possible pre- and postsynaptic mechanisms of this potentiation were discussed.

Animals↗
PubMed1997

Synaptic functions in the aged rat hippocampus: a target for corticosteroids?

The role of corticosteroids in brain aging remains a controversial issue. Conceivably, if corticosteroids levels are increased in the aged brain, neuronal function might be altered. For instance, GABA-mediated synaptic events, spike accommodation and afterhyperpolarizing potentials (AHPs) might be modified. Our electrophysiological results show that the most consistent alterations observed in the aged rat hippocampus concern cholinergic receptors, glutamatergic NMDA receptors and GABAB receptors mediated synaptic potentials. In contrast no consistent alterations were observed in afterhyperpolarizing potentials, calcium spikes, or GABAA mediated synaptic events. Therefore our electrophysiological results are difficult to reconcile with a 'glucocorticoid cascade hypothesis,' involving an elevated level of corticosterone in the aged rat.

Adrenal Cortex Hormones↗
PubMed1996

Deficits in memory and hippocampal long-term potentiation in mice with reduced calbindin D28K expression.

The influx of calcium into the postsynaptic neuron is likely to be an important event in memory formation. Among the mechanisms that nerve cells may use to alter the time course or size of a spike of intracellular calcium are cytosolic calcium binding or "buffering" proteins. To consider the role in memory formation of one of these proteins, calbindin D28K, which is abundant in many neurons, including the CA1 pyramidal cells of the hippocampus, transgenic mice deficient in calbindin D28K have been created. These mice show selective impairments in spatial learning paradigms and fail to maintain long-term potentiation. These results suggest a role for calbindin D28K protein in temporally extending a neuronal calcium signal, allowing the activation of calcium-dependent intracellular signaling pathways underlying memory function.

Animals↗
PubMed1996

Persistence of CA1 hippocampal LTP after selective cholinergic denervation.

The possible role of endogenous cholinergic innervation in hippocampal plasticity is controversial. We studied the role of acetylcholine (ACh) in short- and long-term potentiation (STP and LTP), using the cholinergic neurotoxin 192 IgG-saporin. It was still possible to induce STP the LTP in the CA1 field following complete and selective cholinergic denervation of the hippocampus. This study therefore demonstrates that integrity of the endogenous cholinergic system is not necessary for the induction or maintenance of LTP in the CA1 field of the hippocampus. The consequences in terms of relationship between hippocampal cholinergic system, LTP and memory are discussed.

Acetylcholine↗
PubMed1996

Direct intracerebral nerve growth factor gene transfer using a recombinant adenovirus: effect on basal forebrain cholinergic neurons during aging.

Gene therapy in the nervous system offers an attractive strategy for the administration of therapeutic factors in a potentially region-specific, sustained, and well-tolerated manner. We tested the trophic effect of a recombinant adenovirus encoding nerve growth factor (AdNGF) in vivo on basal forebrain cholinergic neurons of aged rats, a neuronal population affected during normal and pathological aging. Three weeks after unilateral injection of the recombinant adenovirus into the nucleus basalis magnocellularis, a significant increase in the somal areas of cholinergic neurons ipsilateral to the injection was observed. No increase was detected in animals receiving a recombinant adenovirus carrying the Escherichia coli Lac Z reporter gene. Injected animals did not lose weight, an adverse effect usually described after intracerebroventricular infusion of NGF, and no tissue loss or massive local inflammatory response was observed around injection sites. Thus, a single intracerebral injection of AdNGF produces trophic effects similar to those resulting from chronic intracerebroventricular high levels of NGF. These findings indicate that recombinant adenoviruses encoding growth factors are potentially powerful tools for improving neuronal deficits associated with degenerative processes.

Acetylcholine↗
PubMed1996

Synaptic mechanisms and calcium binding proteins in the aged rat brain.

Synaptic mechanisms were studied ex vivo in the aged rat hippocampus, using a slice preparation and intracellular electrophysiological recordings of the CA1 pyramidal neurons. A dramatic depression of the slow cholinergic excitatory postsynaptic potential (EPSP) and of the slow, GABAB-mediated inhibitory postsynaptic potential (IPSP) were observed. These age-related changes were consistently found in three different strains of rats. The mechanisms involve 1) changes in the properties of the postsynaptic muscarinic receptors, and possibly in acetylcholine release (for the postsynaptic muscarinic receptors, and possbily in acetylcholine release (for the cholinergic EPSP), and 2) alterations in the presynaptic GABAergic interneurons, as shown by a loss in calbindin immunoreactivity (for the GABAergic IPSP). The immunoreactivity for three calcium binding proteins (calbindin, parvalbumin and calretinin) was studied in the aged rat brain. Immunoreactivity for calbindin was dramatically reduced in the pyramidal neurons of the CA1 field and in a subpopulation of interneurons in the hippocampus. Immunoreactivity for parvalbumin was reduced in the medial septal area, and in the cingulate cortex, whereas no change was observed for calretinin. These age-related alterations could 1) modify the functions of the hippocampal networks, and possibly contribute to the age-related cognitive deficits, and 2) compromise intraneuronal calcium buffering, and thus make neurons more vulnerable to toxic insults.

Animals↗
PubMed1996

Effects of metrifonate, a cholinesterase inhibitor, on local cerebral glucose utilization in young and aged rats.

The effects of the centrally acting anti-cholinesterase metrifonate (MFT) and its metabolite dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP) on local cerebral glucose utilization (LCGU) have been studied in 3- and 27-month-old rats, using the autoradiographic [14C]deoxyglucose technique. In 3-month-old rats, MFT (80 mg/kg i.p.) increased LCGU significantly in 17 of the 54 regions studied, including insular, cingulate, and temporal cortices, ventral hippocampus, thalamus, lateral habenula, substantia nigra, and superior colliculus. In these regions, the average MFT-induced increase in LCGU was 23% above control. The average hemispheric LCGU increased by 10% (p < 0.01). DDVP (5 mg/kg) increased LCGU in 19 regions (average increase 26%). The average hemispheric LCGU increased by 9% (p < 0.01). Regional distributions of MFT- and DDVP-induced increases in LCGU were similar and overlapped the distribution of the acetylcholinesterase activity. In 27-month-old rats, MFT was active in 18 regions (average increase 25%). The whole-brain mean LCGU increased by 10% (p < 0.01). MFT compensated for the age-related hypometabolism in some brain areas including insular, temporal, and retrosplenial cortices, substantia nigra, and superior colliculus. The effects of MFT on LCGU were preserved in old rats, at variance with other anticholinesterases (tacrine, physostigmine). Which are less active in the aged rat brain.

Aging↗
PubMed1996

Correlations between water maze performance and cortical somatostatin mRNA and high-affinity binding sites during ageing in rats.

Somatostatin levels and high-affinity (somatostatin-1) binding sites are decreased in post-mortem cortical samples of Alzheimer's disease patients but the relationships between such modifications and the cognitive deficits remain to be established. We investigated these relationships in the ageing rat. Three age groups (3-4, 14-15 and 26-27 months) were tested in a modified version of the Morris water maze. Somatostatin mRNA levels were quantified by in situ hybridization and somatostatin binding sites by radioautography using the selective agonist octreotide (SMS 201995) as a competing drug to evaluate high-affinity (somatostatin-1) and low-affinity (somatostatin-2) binding sites. The number of somatostatin mRNA-containing cells was not modified with age or memory performance in cortical, hippocampal and hypothalamic regions, but somatostatin mRNA densities were significantly decreased with age and with memory performance in the frontal and parietal cortex. In the frontal cortex somatostatin mRNA densities were already decreased in 14- to 15-month-old rats, whereas the decrease was observed only in 26- to 27-month-old rats in the parietal cortex. A decrease in somatostatin-1 binding was observed with memory performance, independently of age, in the basolateral amygdala only, while somatostatin-2 binding sites were not affected. In the frontal and parietal cortex, a significant correlation occurred between the latency to find the invisible platform in the water maze and somatostatin mRNA (r = -0.54 and 0.59 respectively, P < 0.02). These results indicate that ageing rats with memory impairments display some of the features of the somatostatinergic deficits observed in Alzheimer's disease.

Aging↗
PubMed1995

Calretinin-containing pathways in the rat forebrain.

The anatomy of pathways containing the calcium binding protein calretinin was investigated in the forebrain of the rat, using a combination of immunohistochemical and retrograde tract tracing techniques. Numerous well identified pathways do contain calretinin, whereas others do not. Pathways arising from the substantia nigra/ventral tegmental area, the dorsal raphe, the lateral mammillary nucleus, the supramammillary nucleus, the triangular septal and septo-fimbrial nuclei, several thalamic nuclei, the parabrachial nucleus, the peripeduncular nucleus, the medial amygdala contain at least some calretinin. The proportion of projection neurons containing calretinin ranged from 2% (dorsal raphe to caudate) to about 75% (triangular septal nucleus to habenula, medial amygdala to the ventromedial hypothalamus). More than 50% of the nigro-striatal neurons contain calretinin immunoreactivity. In contrast, other pathways do not contain any calretinin immunoreactivity (for instance the pathways arising from cerebral cortex, locus coeruleus, cholinergic forebrain nuclei), although calretinin may be present in local neurons in these structures. The present study demonstrates that calretinin is not associated specifically with projection neurons or local neurons, identified transmitter systems or functionally related pathways in the forebrain of the rat.

Amygdala↗
PubMed1995

Metabolic response to tacrine (THA) and physostigmine in the aged rat brain.

The effects of the centrally acting anti-cholinesterases tacrine (tetrahydroaminoacridine, THA) and physostigmine (PHY), on local cerebral glucose utilization (LCGU) have been studied in 27-month-old rats, using the autoradiographic [14C]deoxyglucose technique. THA (10 mg/kg i.p.) increased LCGU significantly in 13 of the 54 regions studied (24%) including insular, parietal, temporal, and retrosplenial cortices, septohippocampal system, thalamus, lateral habenula, and superior colliculus. In these regions, the average THA-induced increase in LCGU was 24% above control. The whole brain mean LCGU was not significantly increased. PHY (0.5 mg/kg) increased LCGU in 18% of the regions (average elevation, 23%). The whole brain mean LCGU increased by 7% (p < 0.05). The regional distributions of THA- and PHY-induced increases in LCGU were extremely similar and overlapped the distribution of the M2 muscarinic receptors and that of acetylcholinesterase activity, suggesting that the major effects of THA and PHY on LCGU result from their anticholinesterase action. As compared to those of 3-month-old rats, both the number of regions affected and the amplitude of the metabolic activation were significantly less in aged rats. However, the drugs were still active in old rats and compensated for the age-related hypometabolism in some brain areas.

Aging↗
PubMed1995

Decreased monosynaptic GABAB-mediated inhibitory postsynaptic potentials in hippocampal CA1 pyramidal cells in the aged rat: pharmacological characterization and possible mechanisms.

1. gamma-Aminobutyric acid (GABA)-mediated inhibitory postsynaptic potentials (IPSPs) were compared in young and aged rats in CA1 area of the rat hippocampus, with the use of the in vitro intracellular recording technique. D-2-Amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were used to suppress synaptic potentials mediated by the excitatory amino acids. 2. Under these conditions, stimulation of the stratum radiatum elicited a monosynaptic fast GABAA (fIPSP) and a slow GABAB (sIPSP)-mediated IPSP. The fIPSP and the sIPSP were further isolated in the presence of the GABAB antagonist CGP 35348 or the GABAA antagonists bicuculline or picrotoxin. No age-related changes were observed in the amplitude and the duration of the fIPSP. In contrast, the amplitude (but not the duration) of the sIPSP was significantly reduced in the aged rat. 3. The postsynaptic hyperpolarization and increase in membrane conductance induced in pyramidal cells by bath application of the GABAB agonist baclofen were comparable in both groups of animals, indicating that the postsynaptic GABAB receptors are not altered in the aged rats. 4. Paired-pulse depression of IPSPs was used in young and aged rats to study possible alterations in GABA release or in presynaptic GABAB receptors that control GABA release. When fIPSPs were isolated by bath application of tetrahydro-9-aminoacridine (THA), no significant difference in the magnitude of the paired-pulse depression was observed between young and aged rats. A similar result was found with the paired-pulse depression of isolated sIPSPs in the presence of bicuculline or picrotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Loss of calbindin-immunoreactivity in CA1 hippocampal stratum radiatum and stratum lacunosum-moleculare interneurons in the aged rat.

Alterations in hippocampal circuitry may underly age-related learning and memory impairment. We showed in a previous study that the GABAB-mediated slow inhibitory postsynaptic potential (IPSP) induced in CA1 pyramidal neurons by electrical stimulation of stratum radiatum, is depressed in the hippocampus of the aged rat. This could be due to alterations in GABAergic interneuron functions. We report in this study that the number of hippocampal calbindin-immunoreactive (CaBP-IR) GABAergic interneurons is decreased in the aged rat. The mean number of CaBP-IR interneurons per slice decreases by 50% in the aged rat. The most severe loss was observed in the stratum radiatum of CA1 (78%), with a less consistent loss of immunoreactivity in CA3 (35%). In contrast, the mean number of interneurons containing parvalbumin (PV), was not significantly decreased in the aged rat. Our results show a loss of CaBP immunoreactivity in a population of GABAergic interneurons, which might be related to an altered function of these interneurons and consequently of GABAergic synaptic transmission in the aged rat. In contrast, PV immunoreactivity in interneurons located close to the pyramidal layer does not decrease in the hippocampus of the aged rat.

Aging↗
PubMed1994

Cholinergic denervation of the rat hippocampus by 192-IgG-saporin: electrophysiological evidence.

The consequences of intracerebroventricular injection of the toxin 192-IgG-saporin on the electrophysiological properties of CA1 pyramidal cells were investigated using intracellular recordings in the in vitro hippocampal slice preparation. We present the first electrophysiological evidence of a dysfunction of hippocampal cholinergic afferents following injection of 192-IgG-saporin. The synaptic events mediated by acetylcholine were altered in such animals: the slow cholinergic excitatory postsynaptic potentials as well as the cholinergic activation of GABAergic interneurones were dramatically depressed or even absent; the amplitude and duration of the afterhyperpolarization following a burst of spikes were increased, while other neuronal properties were not modified. These specific alterations suggest that the toxin 192-IgG-saporin is a specific tool for the experimental study of cholinergic denervation in the hippocampus.

Animals↗
PubMed1994

The age-related increase in galanin binding sites in the rat brain correlates with behavioral impairment.

The regional distribution of [125I]galanin specific binding sites was determined in young (three- to four-month-old), 14-15-month-old and aged (26-27-month-old) male Sprague-Dawley rats, previously tested for their performances in the Morris water-maze task, using the radioautographic method on brain sections. A significant increase in specific binding was observed in piriform and entorhinal cortex, ventral subiculum, and dorsal dentate gyrus in the aged rats, whereas no significant changes were observed in dorsal subiculum, amygdala, septal area and various subcortical structures. The area-specific regional increase in specific binding density in aged rats was significantly correlated with the impairment of the behavioral performance in the Morris water-maze task. The change in [125I]galanin specific binding was a result of an increase in the number of galanin binding sites, but not of an increase in affinity.

Aging↗
PubMed1994

Alzheimer's disease: a review of recent findings.

The recent development of biological research on dementias of the Alzheimer's type has lead to a better understanding of their pathophysiology. We know the nature of the proteins present in senile plaques and in the neurofibrillary degeneration. Pathophysiological hypotheses are more precise, and clearly involve genetic factors. The rapid progress in this field raises the hope that more efficient treatments will appear in the near future.

Acetylcholine↗