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Biomedical subjects

M Baudry

Publications and source records attributed to M Baudry.

At least 145 records · Page 8Linked to original sources
PubMed1991

Effect of treatment with difluoromethylornithine on polyamine and spectrin breakdown levels in neonatal rat brain.

Impairment of polyamine synthesis by treatment with difluoromehtylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been shown to alter normal brain development. In the present study we determined the effect of DFMO treatment during a discrete developmental period on polyamine levels and on the in situ activity of calpain, as reflected by the level of degradation of spectrin, in various brain regions of rat pups. DFMO treatment from postnatal days 5 to 10 produced a marked decrease in putrescine levels in every brain structure and a significant decrease in spectrin breakdown levels in hippocampus and cortex but not in cerebellum. The results indicate that the ODC/polyamine pathway partly regulates the in situ activity of calpain and that polyamines may play a role in both growth and degeneration phenomena.

Animals↗
PubMed1991

Classical conditioning selectively increases AMPA receptor binding in rabbit hippocampus.

The NMDA and AMPA receptors have been shown to play critical roles in various forms of synaptic plasticity (learning and memory, long-term potentiation). The present study investigated the involvement of these two receptors in a well-characterized classical conditioning paradigm. Following classical conditioning of the rabbit nictitating membrane the binding properties of these two subclasses of excitatory amino acid transmitter receptors were analyzed in dorsal hippocampi by quantitative autoradiography. [3H] TCP and [3H] AMPA were used to identify the NMDA and AMPA receptors, respectively. The binding of [3H]TCP to the NMDA receptor remained unchanged in all the experimental groups tested. Paired presentations of the conditioned and unconditioned stimuli resulted in increased [3H] AMPA binding to the AMPA receptor in several subfields of the hippocampus, while unpaired presentations had no significant effects. The increase in binding was due to an increased affinity of the low-affinity component of the AMPA receptor. The results support the hypothesis that changes in glutamate receptors participate in the synaptic plasticity involved in certain forms of learning.

Animals↗
PubMed1991

Selective increase of AMPA binding to the AMPA/quisqualate receptor in the hippocampus in response to acute stress.

The binding properties of ligands specific for two subclasses of glutamate receptors were studied by quantitative autoradiography after one hour of acute immobilization/shock stress. [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine (TCP) and [3H]alpha-amino-3-methylisoxazole-4-propionic acid (AMPA) were used to visualize the N-methyl-D-aspartate receptor and the AMPA/quisqualate receptor types, respectively. While no change was observed in the binding properties of the [3H]TCP, [3H]AMPA binding was significantly increased in several areas of the hippocampus of acutely stressed rats relative to naive controls.

Animals↗
PubMed1991

Opposite effects of phospholipase A2 on [3H]AMPA binding in adult and neonatal membranes.

In the present study, we compared the effect of phospholipase A2 (PLA2) treatment of synaptic membranes from adult and neonatal rats on the characteristics of [3H]AMPA binding sites. Whereas PLA2 treatment of membranes from adult rats produces an increased affinity for [3H]AMPA binding, the same treatment in neonatal rats results in a decrease in the maximal number of binding sites. Since activation of PLA2 has been proposed to play a critical role in the formation of long-term potentiation (LTP), possibly mediated through a modification of the AMPA receptors, the results strengthen the hypothesis that PLA2-induced modification of [3H]AMPA binding sites is an important component of synaptic plasticity.

Aging↗
PubMed1991

Entorhinal cortex lesion or intrahippocampal colchicine injection increases peripheral type benzodiazepine binding sites in rat hippocampus.

The peripheral type benzodiazepine binding site (PTBBS) has been proposed to be a good marker for reactive glial cells following brain insults. In the present study, homogenate binding of 3H-Ro5-4864 and quantitative autoradiography of 3H-PK-11195 binding (two ligands for the PTBBS) were used to assess the distribution, time-course and extent of reactive gliosis in the hippocampus following deafferentation by unilateral entorhinal cortex lesion or neuronal death produced by intrahippocampal colchicine injection. Intrahippocampal colchicine injections produced a 3-fold increase in 3H-Ro5-4864 binding in the dentate gyrus within 2 days. This effect was doubled in animals pretreated with the lysosomal inhibitor chloroquine. Quantitative autoradiography of 3H-PK-11195 binding 1 or 2 weeks after colchicine injection indicated that the increase in binding was restricted to the dorsal hippocampus both rostrally and caudally and was present in the dentate gyrus and CA1. Following a unilateral electrolytic lesion of the entorhinal cortex, the binding of 3H-Ro5-4864 to homogenates of the dentate gyrus was doubled 18 h after the lesion, reached a maximum at 4 days post-lesion, and returned to control values by 2 months after the lesion. A transient increase in binding was also observed 2 and 4 days post-lesion in the dentate gyrus contralateral to the lesion side. Autoradiography of 3H-PK-11195 binding indicated that the increase in PTBBS following entorhinal cortex lesion was restricted to the molecular layer of the dentate gyrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Modulation of DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/quisqualate receptors by phospholipase A2: a necessary step in long-term potentiation?

The effects of kainate (KA)-induced epileptic seizures on the binding properties of hippocampal glutamate receptors, on the modulation of DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/quisqualate receptor by phospholipase A2 (PLA2), and on the formation of long-term potentiation (LTP) were studied in hippocampal membranes and hippocampal slices. Systemic administration of KA (10 mg/kg; 15 hr survival) produced specific changes in the binding properties of the AMPA/quisqualate receptors and its regulation. Whereas the binding of various ligands to the N-methyl-D-aspartate receptors was not modified by KA treatment, there was a significant decrease in the maximal number of binding sites for [3H]AMPA. In addition, the increase in [3H]AMPA binding elicited by PLA2 treatment of hippocampal, but not cerebellar, membranes was markedly decreased after KA injection. LTP was also substantially reduced in area CA1 of hippocampal slices from KA-treated animals. The loss of LTP was not due to changes in postsynaptic responses elicited by the bursts that trigger the potentiation effect, thus suggesting that KA treatment disrupts processes that follow N-methyl-D-aspartate receptor activation. Systemic administration of KA was associated with calpain activation as the amount of spectrin breakdown products was increased severalfold in hippocampus but not in cerebellum. Pretreatment of telencephalic membranes with calpain greatly reduced the PLA2-induced increase in [3H]AMPA binding. The results provide evidence in favor of an essential role of PLA2 in the development of LTP and suggest that the order of activation of different calcium-dependent processes is critical for producing the final changes underlying LTP.

Animals↗
PubMed1991

Phosphatidylserine increases the affinity of the AMPA/quisqualate receptor in rat brain membranes.

We investigated the effects of phospholipids and cholesterol on the binding of [3H]-AMPA to rat telencephalic membranes. Phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and cholesterol were without effect at concentrations up to 1.5 mg/mg protein. Only phosphatidylserine increased [3H]-AMPA binding in a dose-dependent manner. This effect was due to an increase in the affinity of the low affinity component of [3H]-AMPA binding. These results indicate that the distribution of phosphatidylserine in membranes modulates the properties of the AMPA/quisqualate receptor.

Animals↗
PubMed1991

Triggers and substrates of hippocampal synaptic plasticity.

It is widely assumed that behavioral learning reflects adaptive properties of the neuronal networks underlying behavior. Adaptive properties of networks in turn arise from the existence of biochemical mechanisms that regulate the efficacy of synaptic transmission. Considerable progress has been made in the elucidation of the mechanisms involved in synaptic plasticity at central synapses and especially those responsible for the phenomenon of long-term potentiation (LTP) of synaptic transmission in hippocampus. While the nature and the timing requirements of the triggering steps are reasonably well known, there is still a lot of uncertainty concerning the mechanisms responsible for the long-term changes. Several biochemical processes have been proposed to play critical roles in promoting long-lasting modifications of synaptic efficacy. This review examines first the triggers that are necessary to produce LTP in the hippocampus and then the different biochemical processes that have been considered to participate in the maintenance of LTP. Finally, we examine the relationships between LTP and behavioral learning.

Animals↗
PubMed1991

Differential effects of ketamine and MK-801 on the induction of long-term potentiation.

Ketamine and MK-801 are phencyclidine (PCP)-like noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor that produce a use-dependent blockade of the NMDA receptor-coupled channel. Recent studies have suggested that the binding properties of these drugs to the NMDA receptor in-vitro are different. In the present study, the effects of ketamine and MK-801 on the induction of long-term potentiation (LTP) were compared at perforant path--granule cell synapses in anaesthetized rats. LTP was observed in animals treated with either saline or MK-801, but not in those treated with ketamine. These results reveal that ketamine and MK-801 differentially modulate the induction of LTP, and we propose that this differential modulation may be related to the different binding properties of the drugs.

Animals↗
PubMed1991

Complex interactions between polyamines and calpain-mediated proteolysis in rat brain.

Polyamine synthesis is induced by various extracellular signals, and it is widely held that this biochemical response participates in cell growth and differentiation. Certain of the triggers for synthesis in brain tissues also increase the breakdown of high-molecular-weight structural proteins, apparently by activating calcium-dependent proteases (calpains). The present experiments tested the possibility that calpain activity is modulated by polyamines. Spermine, spermidine, and putrescine all increased calcium-dependent proteolysis of [14C]casein by soluble fractions of rat brain. The order of potency was spermine greater than spermidine greater than putrescine, with apparent affinities of 30, 300, and 6,000 microM, respectively. Each of the three polyamines at physiological concentrations also potentiated the calcium-dependent breakdown of two endogenous high-molecular-weight structural proteins known to be substrates of calpain, in both supernatant and membrane fractions. The thiol protease inhibitor leupeptin, a known calpain inhibitor, also inhibited calcium-dependent proteolysis in the presence and absence of polyamines. The polyamines did not increase the activity of purified calpain I or calpain II determined with either [14C]casein or purified spectrin as the substrate, nor did they interfere with the inhibitory effects of calpastatin, an endogenous inhibitor of calpain. However, polyamines potentiated the stimulation of endogenous but not purified calpain activity produced by an endogenous calpain activator. These results suggest a role for polyamines in protein degradation as well as protein synthesis.

Animals↗
PubMed1990

Effect of bromophenacyl bromide, a phospholipase A2 inhibitor, on the induction and maintenance of LTP in hippocampal slices.

The effect of bromophenacyl bromide (BPB), a phospholipase A2 (PLA2) inhibitor, on both the induction and the maintenance of long-term potentiation (LTP) was investigated in field CA1 of the hippocampal slice preparation. One hour of BPB application (50 microM) caused a large reduction in the magnitude of LTP induced by a theta burst stimulation (TBS) paradigm. BPB had no significant effect on either the degree of paired-pulse facilitation or the amount of pre-established LTP. Furthermore, the facilitation of postsynaptic responses occurring during TBS and in the first minute following TBS was not reduced by the PLA2 inhibitor. These results indicate that the inhibition of LTP produced by BPB is not due to an effect of the drug on a physiological event that triggers LTP. The data also suggest that PLA2 activation plays a critical role in the expression of LTP, but is not required for the maintenance of the potentiation.

Acetophenones↗
PubMed1990

Modulation of DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/quisqualate receptors by phospholipase A2 treatment.

The expression of long-term potentiation (LTP) in area CA1 of hippocampus has been proposed to result from an increased sensitivity of the AMPA/quisqualate receptors. We have investigated the binding properties of excitatory amino acid receptors in phospholipase A2 (PLA2)-treated rat brain membranes. PLA2 from bee venom produced a significant increase in the binding of [3H]-AMPA ([3H]-amino-3-hydroxy-5-methylisoxazole-4- propionate), a ligand for the AMPA/quisqualate receptor. Analysis of the saturation kinetics revealed that PLA2 treatment increased the affinity of the AMPA/quisqualate receptor without changing the maximum number of sites. In contrast, PLA2 treatment did not detectably modify the binding of [3H]-kainate to the kainate receptor and of [3H]-glutamate and [3H]-glycine to the NMDA (N-methyl-D-aspartate) receptor complex. These finding suggest that phospholipase A2 may regulate the AMPA/quisqualate receptor and could play an important role in the development of LTP.

Animals↗
PubMed1990

Regional differences in the activation of synaptosomal mitochondrial Ca2+ uptake by spermine in rat brain.

Several properties of Ca2+ uptake by isolated synaptosomal mitochondria were characterized by using a repetitive Ca2+ loading technique. Synaptosomal mitochondria maintained extramitochondrial Ca2+ concentration at submicromolar levels when challenged with successive additions of small amounts of Ca2+. Ca2+ uptake under these conditions was markedly stimulated by the presence of spermine, a polyamine found in high concentrations in brain. Moreover, mitochondria isolated from telencephalic areas of rat brain were activated to a greater extent by spermine than were mitochondria from non-telencephalic brain regions. The present results support the idea that brain mitochondria could play a significant role in limiting the intraneuronal rise in Ca2+ that follows stimulation or injury. In addition, telencephalic mitochondria exhibit more flexibility in the regulation of Ca2+ uptake than do mitochondria from phylogenetically older non-telencephalic brain regions and this could be related to differences in Ca2+ influx mechanisms in these brain regions.

Animals↗
PubMed1990

Distribution of calcium-activated protease calpain in the rat brain.

Calpain is a calcium-activated neutral protease that degrades a number of cytoskeletal proteins. It may participate in the maintenance of the cytoskeleton and in the rapid turnover of structural proteins associated with synaptic plasticity. Calpain may also be involved in the neurodegeneration that accompanies aging and age-related diseases. To aid in the interpretation of disease-related alterations in staining patterns, the present study examined calpain's normal distribution in the mammalian brain and spinal cord. A monoclonal antibody was employed with the avidin-biotin-peroxidase immunocytochemical technique on samples of rat tissue. Glia (astrocytes, microglia) and virtually all neurons were immunopositive, although neuronal processes exhibited varying staining patterns. The axonal staining pattern depended upon either the origin or destination of the process: those axons remaining within the brain (e.g., corpus callosum) were only lightly immunoreactive, whereas spinal cord and peripheral axons (trigeminal nerve) were more darkly labeled. The architecture of the dendritic tree determined the dendritic staining pattern: neurons with prominent apical and basal dendritic trees (e.g., pyramidal cells) were immunolabeled along their entire extent; labeling of multipolar cells (e.g., hilar cells of dentate gyrus) was limited to the proximal dendrites. The ubiquitous distribution of calpain argues against a primary role for the enzyme in the regional pattern of neuronal death seen in Alzheimer's disease. An alteration in the concentration, localization, or inhibition of the enzyme could, however, lead to the abnormal accumulations of cytoskeletal elements seen with the disease.

Animals↗
PubMed1990

Role of excitatory amino acid neurotransmission in synaptic plasticity and pathology. An integrative hypothesis concerning the pathogenesis and evolutionary advantages of schizophrenia-related genes.

N-methyl-D-aspartate (NMDA) receptors are involved in long-term potentiation, burst firing and the generation of patterned activity in neuronal networks; in use-dependent stabilization of synaptic connectivity in developing animals; in some forms of learning in mature animals; and in pathologies as found in brain aging. A number of these characteristics are reminiscent of several manifestations of schizophrenia and therefore we present the hypothesis that one of the genes modified in schizophrenia is directly or indirectly linked to the control of excitatory neurotransmission; possibly the normal switching on of the expression of the adult form of the NMDA receptor is delayed. Alternatively the adult form of the NMDA receptor is altered, resulting in inappropriate functioning of this receptor. The delayed or faulty expression of the adult form of the NMDA receptor, in turn, should confer a series of evolutionary advantages including protection against aging-associated brain pathologies.

Amino Acids↗
PubMed1990

Induction of ornithine decarboxylase by subseizure stimulation in the hippocampus in vivo.

Electrical stimulation of the Schaffer-collateral axonal system under conditions which do not elicit detectable seizure activity causes an increase in the activity of ornithine decarboxylase (ODC), the rate limiting enzyme of polyamine synthesis, in the hippocampus, olfactory cortex, neocortex and olfactory bulb. The degree of ODC activation is dependent upon the stimulus parameters. The results support the hypothesis that neuronal activity regulates hippocampal polyamine concentrations.

Animals↗
PubMed1990

Systemic injection of kainic acid: gliosis in olfactory and limbic brain regions quantified with [3H]PK 11195 binding autoradiography.

Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of [3H]PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in [3H]PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in [3H]PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of [3H]PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in [3H]PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of [3H]PK 11195 is a valuable tool to quantify the extent of neuronal degeneration. Furthermore, the quantitative changes in [3H]PK 11195 binding in different limbic structures parallel their relative variation in neuropathology observed in Alzheimer's disease but not Huntington's chorea. These findings are in agreement with the idea that excessive stimulation of excitatory amino receptors may contribute to the etiology of Alzheimer's disease.

Animals↗