S N Schiffmann | Université libre de Bruxelles (original) (raw)
Papers by S N Schiffmann
New England Journal of Medicine, 1992
Neuroscience Letters, 1993
The distributions of adenosine A2 receptor mRNA and adenosine A2 binding sites were studied by in... more The distributions of adenosine A2 receptor mRNA and adenosine A2 binding sites were studied by in situ hybridization histochemistry and receptor autoradiography in young (3 months) and old (24 months) rat striatum and compared to that of enkephalin mRNA. In the old striatum, the levels of adenosine A2 receptor mRNA and adenosine A2 binding sites were reduced by 32% and 20%, respectively. This decrease is similar to the 24% decrease of enkephalin mRNA and to the previously reported 20% neuronal loss. This indicated that, in contrast to the dopamine D2 receptor, the reduction of adenosine A2 receptors in the rat striatum during aging is mainly due to the neuronal loss.
Neuroscience Letters, 1992
The distribution of cholecystokinin binding sites was studied by receptor autoradiography in the ... more The distribution of cholecystokinin binding sites was studied by receptor autoradiography in the human striatum at midgestation, birth and adulthood. In the adult, cholecystokinin receptors are inhomogeneously distributed with patches of reduced labeling. In the caudate nucleus but not in the putamen these patches match the striosomal organization as revealed by acetylcholinesterase staining. At midgestation, patches of high density of cholecystokinin receptors are in register with the dopamine D~ receptor-enriched stri0somes. At birth, this striosomal organization has already evolved into the adult pattern of higher matrix level in contrast to the striosomal pattern of acetylcholinesterase staining.
NeuroReport, 2000
Most effects of nociceptin are related to blockade of stress and anxiolytic-like effects. This ne... more Most effects of nociceptin are related to blockade of stress and anxiolytic-like effects. This neuropeptide is highly expressed in septal nuclei, which are involved in response to stressful situations. Dopamine and adenosine may have modulatory effects on stress behaviour by acting on septal neurons. We therefore analysed the regulation of septal nociceptin expression using quantitative in situ hybridization following manipulations of adenosine and dopamine neurotransmission. No difference was observed between wild-type and A 2A receptor-de®cient mice. In both genotypes, chronic treatments with caffeine, an equipotent A 1 and A 2A adenosine receptor antagonist, did not signi®cantly modify nociceptin expression. 6-Hydroxydopamine-induced dopamine depletion was also without effect. These results demonstrate that dopamine and adenosine are not involved in the regulation of septal nociceptin expression in spite of the involvement of these three neurotransmitters in stress and anxiety behaviours.
Neurochemistry International, 1989
By immunohistochemistry, a large number of neurotensin immunoreactive nerve terminals are found i... more By immunohistochemistry, a large number of neurotensin immunoreactive nerve terminals are found in the kitten inferior olive of the medulla oblongata. They are present in the dorsal lamella of the principal olive, in the ventrolateral outgrowth and in the medial part of the caudal dorsal accessory olive. They are absent in the medial accessory olive. They disappear in the adult cat. Neurotensin immunoreactivity is absent in the developing rat inferior olive. This localization in the cat suggests a neuronal origin in the mesencephalon, mainly in the red nucleus. These results confirm our recent report on a transient large neurotensinergic innervation of the human developing principal olive.
Journal of Neurochemistry, 1991
RDC8 has been recently cloned and characterized as an adenosine A2 receptor. This receptor is exp... more RDC8 has been recently cloned and characterized as an adenosine A2 receptor. This receptor is expressed exclusively by medium‐sized neurons of the striatum as demonstrated by in situ hybridization. We have now studied the relationship of this receptor with three major components of the rat caudate‐putamen: enkephalin, substance P, and choline acetyltransferase. Our results demonstrate that the adenosine A2 receptor is expressed exclusively by the enkephalinergic striatal subpopulation but not by the substance P‐containing or cholinergic neurons.
Journal of Comparative Neurology, 1991
The distribution of cells containing mRNA encoding cholecystokinin was studied in the rat central... more The distribution of cells containing mRNA encoding cholecystokinin was studied in the rat central nervous system by in situ hybridization histochemistry.Cholecystokinin mRNA containing neurons were considerably more numerous than the cholecystokinin‐like immunoreactive neurons detected by immunocytochemistry even after cholchicine pretreatment and appeared to be heavily, moderately, or lightly labeled. Such neurons were present in the olfactory bulb, olfactory nuclei, layers II–III and V–VI of the cerebral cortex, amygdaloïdnuclei, subiculum, hippocampus, claustrum, endopiriform nucleus, several hypothalamic nuclei, most of the thalamic nuclei, ventral tegmental area, substantia nigra, interfascicularis nucleus, linearis rostralis, central gray, Edinger‐Westphal nucleus, superior and inferior colliculi, parabrachial nucleus, reticular formation, raphe nuclei, and spinal trigeminal nucleus.This distribution partly confirmed and partly extended the previous immunohistochemical descrip...
European Journal of Neuroscience, 1995
We used in situ hybridization to investigate the effect of complete visual deafferentation on imm... more We used in situ hybridization to investigate the effect of complete visual deafferentation on immediate early gene expression in adult cat visual cortex. Deafferentation was obtained by unilateral section of the optic tract and sections of both the corpus callosum and anterior commissure. In this model, one hemisphere served as control for the other within the same animal. A decrease in zinc finger protein (zif)‐268 and c‐fos mRNA was observed in the superficial and deep layers of areas 17 and 18, and all layers of area 19 in the deafferented hemisphere. This decrease, present 3 days after surgery, was maximal after 30 days. An increase of c‐jun mRNA was observed in the deep layers of areas 17, 18 and 19 in the deafferented hemisphere 3, 10 and 30 days after surgery. These results suggest that visual input activates zif‐268 and c‐fos expression and tonically depresses c‐jun expression in the primary visual complex yielding similar levels of c‐jun and c‐fos expression in normal condi...
Cellular Signalling, 2012
The function of the phosphoinositide 5-phosphatase Ship2 was investigated in a new mouse model ex... more The function of the phosphoinositide 5-phosphatase Ship2 was investigated in a new mouse model expressing a germline catalytically-inactive Ship2 Δ/Δ mutant protein. Ship2 Δ/Δ mice were viable with defects in somatic growth and in development of muscle, adipose tissue and female genital tract. Lipid metabolism and insulin secretion were also affected in these mice, but glucose tolerance, insulin sensitivity and insulin-induced PKB phosphorylation were not. We expected that the expression of the catalytically inactive Ship2 protein in PI 3′-kinase-defective p110α D933A/+ mice would counterbalance the phenotypes of parental mice by restoring normal PKB signaling but, for most of the parameters tested, this was not the case. Indeed, often, the Ship2 Δ/Δ phenotype had a dominant effect over the p110α D933A/+ phenotype and, sometimes, there was a surprising additive effect of both mutations. p110α D933A/+ Ship2 Δ/Δ mice still displayed a reduced PKB phosphorylation in response to insulin, compared to wild type mice yet had a normal glucose tolerance and insulin sensitivity, like the Ship2 Δ/Δ mice. Together, our results suggest that the Ship2 Δ/Δ phenotype is not dependent on an overstimulated class I PI 3-kinase-PKB signaling pathway and thus, indirectly, that it may be more dependent on the lack of Ship2-produced phosphatidylinositol 3,4-bisphosphate and derived phosphoinositides.
Anatomy and Embryology, 1992
Pleiotrophin (PTN), also known as HB-GAM, belongs to an emerging cytokine family unrelated to oth... more Pleiotrophin (PTN), also known as HB-GAM, belongs to an emerging cytokine family unrelated to other growth factors. We report here the first comprehensive study using in situ hybridization on the cellular distribution of this new heparin-binding growth factor mRNA in rat tissues. PTN mRNA was developmentally expressed in many-but not all-neuroectodermal and mesodermal lineages, whilst no PTN mRNA was detected in endoderm, ectoderm and trophoblast. PTN mRNA was found in the nervous system throughout development, with a post-natal peak of expression. In the adult nervous system, significant expression persisted in hippocampal CA1 pyramidal neurons and in cortical neurons, but also in different non-neuronal cells types in various locations (olfactory nerve, cerebellar astrocytes, pituicytes, Schwann cells surrounding the neurons in sensory ganglia). PTN mRNA was also found during development in the mesenchyme of lung, gut, kidney and reproductive tract, in bone and cartilage progenitors, in dental pulp, in myoblasts, and in several other sites. Expression was differently regulated in each location, but usually faded around birth. In the adult, PTN mRNA was still present in the meninges, the iris, the Leydig cells of the testis and in the uterus. PTN mRNA was also strongly expressed in the basal layers of the tongue epithelium, which is the only epithelium and ectodermal derivative to express PTN mRNA, and this only after birth. PTN is known to be a growth factor for perinatal brain neurons and a mitogen for fibroblasts in vitro. Recently, trophic effects on epithelial cells and a role as a turnout growth factor have been reported. The mechanisms of regulation and the functions of PTN are however still uncertain. Its expression pattern during development suggests important roles in growth and differentiation. Moreover, the presence of PTN mRNA in several adult tissues and the up-regulation of PTN mRNA expression in the gravid uterus indicate that PTN also has physiological functions during adulthood.
Acta Neuropathologica, 1988
Using immunohistochemistry, well-preserved neuronal cell bodies and fibres containing neuropeptid... more Using immunohistochemistry, well-preserved neuronal cell bodies and fibres containing neuropeptide Y, somatostatin, and cholecystokinin immunoreactivity have been identified in all seven supratentorial anaplastic astrocytomas studied. These neurones have been shown not only on the edge but also in the depth of the neoplastic tissue. These neuropeptides were not present in 18 other intracranial tumours (3 astrocytomas, 1 subependymoma, 8 glioblastoma multiformes, 1 meningioma, and 5 metastases). In all 25 intracranial tumours studied, no immunoreactivity was found for vasoactive intestinal polypeptide, substance P, methionine-enkephalin, leucine-enkephalin, synenkephalin, neurophysin I-II, and corticotropin releasing factor.
European Journal of Neuroscience, 1998
DARPP-32 is a cyclic adenosine monophosphate-regulated inhibitor of protein phosphatase 1, highly... more DARPP-32 is a cyclic adenosine monophosphate-regulated inhibitor of protein phosphatase 1, highly enriched in striatonigral neurons. Stimulation of dopamine D 1 receptors increases phosphorylation of DARPP-32, whereas glutamate acting on N-methyl-D-aspartate receptors induces its dephosphorylation. Yet, to date, there is little direct evidence for the function of DARPP-32 in striatal neurons. Using a whole cell patch-clamp technique, we have studied the role of DARPP-32 in the regulation of voltage-gated sodium channels in rat striatal neurons maintained in primary culture. Injection of phospho-DARPP-32, but not of the unphosphorylated form, reduced the sodium current amplitude. This effect was similar to those induced by okadaic acid, with which there was no additivity and by tautomycin. Our results indicate that, in striatal neurons, sodium channels are under dynamic control by phosphorylation/dephosphorylation, and that phospho-DARPP-32 reduces sodium current by stabilizing a phosphorylated state of the channel or an associated regulatory protein. We propose that the DARPP-32-mediated modulation of sodium channels, via inhibition of phosphatase 1, contributes to the regulation of these channels by D 1 receptors and other neurotransmitters which influence the state of phosphorylation of DARPP-32. Additional actions of dopamine receptors have also been reported (see for review Lledo et al., 1994), including direct inhibition of Ca 2ϩ channels (Lledo et al., 1992), stimulation of voltage-dependent
Journal of neural transmission. Supplementum, 1991
Neuropeptide and neurotransmitter plasticity has been demonstrated in the central nervous system.... more Neuropeptide and neurotransmitter plasticity has been demonstrated in the central nervous system. Modifications of their synthesis occur following receptor blockade or deafferentiation by surgical lesions. This concept should provid answers to some remaining open questions in human pathology especially in degenerative diseases of the basal ganglia. In a severely atrophied striatum we observed a selective increase in the number of detectable striatal substance P and met-enkephalin neurones which exhibited a striking increase in the intensity of labelling. This increase, instead of the well established reduction of substance P and enkephalins in the atrophied striatum of Huntington's disease, could explain the absence of choreoathetosis which was replaced by rigidity and bradykinesia in the patient. The absence of choreoathetosis, despite severe striatal atrophy, is described in several basal ganglia diseases and could also be related to neurotransmitter or neuropeptide plasticity...
The Journal of Neuroscience, 2003
Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in t... more Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recordedin vivothrough unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mmof the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restore t...
Advances in Experimental Medicine and Biology
ABSTRACT
Bulletin et mémoires de l'Académie royale de médecine de Belgique, 2009
The striatum, the first relay of the basal ganglia system, is critically involved in motor functi... more The striatum, the first relay of the basal ganglia system, is critically involved in motor functions and motivational processes. The dorsal striatum is central to the motor control and motor learning and the ventral striatum or nucleus accumbens is essential for motivation, the reward system and reinforcement by drugs. This system is dysfunctional in movement disorders such as Parkinson's disease and Huntington's disease and in psychiatric disorders including drug addiction. The striatum consists of two populations of neurons projecting at the origin of two distinct paths in the circuit of basal ganglia, and of different populations of interneurons. These two populations of efferent neurons, striatopallidal and striatonigral neurons, are characterized by their projection sites and their differential expression in dopamine receptors and neuropeptides. Their roles in motor control and motivational processes and in the mechanisms of neuroadaptation in the system's pathologi...
Progress in brain research, 2005
Calcium binding proteins, such as calretinin, are abundantly expressed in distinctive patterns in... more Calcium binding proteins, such as calretinin, are abundantly expressed in distinctive patterns in the central nervous system but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin deficient mice exhibit dramatic alterations in motor coordination and in Purkinje cell firing recorded in vivo through unknown mechanisms. In the present paper, we review the results obtained with the patch clamp recording techniques in acute slice preparation. This data allow us to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mM of t...
Frontiers in Molecular Neuroscience, 2012
Calcium binding proteins, such as parvalbumin (PV), are abundantly expressed in distinctive patte... more Calcium binding proteins, such as parvalbumin (PV), are abundantly expressed in distinctive patterns in the central nervous system but their physiological function remains poorly understood. Notably, at the level of the striatum, where PV is only expressed in the fast-spiking (FS) interneurons. FS interneurons form an inhibitory network modulating the output of the striatum by synchronizing medium-sized spiny neurons (MSN). So far the existing conductance-based computational models for FS neurons did not allow the study of the coupling between PV concentration and electrical activity. In the present paper, we propose a new mathematical model for the striatal FS interneurons that includes apamin-sensitive small conductance Ca 2+-dependent K + channels (SK) and the presence of a calcium buffer. Our results show that a variation in the concentration of PV can modulate substantially the intrinsic excitability of the FS interneurons and therefore may be involved in the information processing at the striatal level.
New England Journal of Medicine, 1992
Neuroscience Letters, 1993
The distributions of adenosine A2 receptor mRNA and adenosine A2 binding sites were studied by in... more The distributions of adenosine A2 receptor mRNA and adenosine A2 binding sites were studied by in situ hybridization histochemistry and receptor autoradiography in young (3 months) and old (24 months) rat striatum and compared to that of enkephalin mRNA. In the old striatum, the levels of adenosine A2 receptor mRNA and adenosine A2 binding sites were reduced by 32% and 20%, respectively. This decrease is similar to the 24% decrease of enkephalin mRNA and to the previously reported 20% neuronal loss. This indicated that, in contrast to the dopamine D2 receptor, the reduction of adenosine A2 receptors in the rat striatum during aging is mainly due to the neuronal loss.
Neuroscience Letters, 1992
The distribution of cholecystokinin binding sites was studied by receptor autoradiography in the ... more The distribution of cholecystokinin binding sites was studied by receptor autoradiography in the human striatum at midgestation, birth and adulthood. In the adult, cholecystokinin receptors are inhomogeneously distributed with patches of reduced labeling. In the caudate nucleus but not in the putamen these patches match the striosomal organization as revealed by acetylcholinesterase staining. At midgestation, patches of high density of cholecystokinin receptors are in register with the dopamine D~ receptor-enriched stri0somes. At birth, this striosomal organization has already evolved into the adult pattern of higher matrix level in contrast to the striosomal pattern of acetylcholinesterase staining.
NeuroReport, 2000
Most effects of nociceptin are related to blockade of stress and anxiolytic-like effects. This ne... more Most effects of nociceptin are related to blockade of stress and anxiolytic-like effects. This neuropeptide is highly expressed in septal nuclei, which are involved in response to stressful situations. Dopamine and adenosine may have modulatory effects on stress behaviour by acting on septal neurons. We therefore analysed the regulation of septal nociceptin expression using quantitative in situ hybridization following manipulations of adenosine and dopamine neurotransmission. No difference was observed between wild-type and A 2A receptor-de®cient mice. In both genotypes, chronic treatments with caffeine, an equipotent A 1 and A 2A adenosine receptor antagonist, did not signi®cantly modify nociceptin expression. 6-Hydroxydopamine-induced dopamine depletion was also without effect. These results demonstrate that dopamine and adenosine are not involved in the regulation of septal nociceptin expression in spite of the involvement of these three neurotransmitters in stress and anxiety behaviours.
Neurochemistry International, 1989
By immunohistochemistry, a large number of neurotensin immunoreactive nerve terminals are found i... more By immunohistochemistry, a large number of neurotensin immunoreactive nerve terminals are found in the kitten inferior olive of the medulla oblongata. They are present in the dorsal lamella of the principal olive, in the ventrolateral outgrowth and in the medial part of the caudal dorsal accessory olive. They are absent in the medial accessory olive. They disappear in the adult cat. Neurotensin immunoreactivity is absent in the developing rat inferior olive. This localization in the cat suggests a neuronal origin in the mesencephalon, mainly in the red nucleus. These results confirm our recent report on a transient large neurotensinergic innervation of the human developing principal olive.
Journal of Neurochemistry, 1991
RDC8 has been recently cloned and characterized as an adenosine A2 receptor. This receptor is exp... more RDC8 has been recently cloned and characterized as an adenosine A2 receptor. This receptor is expressed exclusively by medium‐sized neurons of the striatum as demonstrated by in situ hybridization. We have now studied the relationship of this receptor with three major components of the rat caudate‐putamen: enkephalin, substance P, and choline acetyltransferase. Our results demonstrate that the adenosine A2 receptor is expressed exclusively by the enkephalinergic striatal subpopulation but not by the substance P‐containing or cholinergic neurons.
Journal of Comparative Neurology, 1991
The distribution of cells containing mRNA encoding cholecystokinin was studied in the rat central... more The distribution of cells containing mRNA encoding cholecystokinin was studied in the rat central nervous system by in situ hybridization histochemistry.Cholecystokinin mRNA containing neurons were considerably more numerous than the cholecystokinin‐like immunoreactive neurons detected by immunocytochemistry even after cholchicine pretreatment and appeared to be heavily, moderately, or lightly labeled. Such neurons were present in the olfactory bulb, olfactory nuclei, layers II–III and V–VI of the cerebral cortex, amygdaloïdnuclei, subiculum, hippocampus, claustrum, endopiriform nucleus, several hypothalamic nuclei, most of the thalamic nuclei, ventral tegmental area, substantia nigra, interfascicularis nucleus, linearis rostralis, central gray, Edinger‐Westphal nucleus, superior and inferior colliculi, parabrachial nucleus, reticular formation, raphe nuclei, and spinal trigeminal nucleus.This distribution partly confirmed and partly extended the previous immunohistochemical descrip...
European Journal of Neuroscience, 1995
We used in situ hybridization to investigate the effect of complete visual deafferentation on imm... more We used in situ hybridization to investigate the effect of complete visual deafferentation on immediate early gene expression in adult cat visual cortex. Deafferentation was obtained by unilateral section of the optic tract and sections of both the corpus callosum and anterior commissure. In this model, one hemisphere served as control for the other within the same animal. A decrease in zinc finger protein (zif)‐268 and c‐fos mRNA was observed in the superficial and deep layers of areas 17 and 18, and all layers of area 19 in the deafferented hemisphere. This decrease, present 3 days after surgery, was maximal after 30 days. An increase of c‐jun mRNA was observed in the deep layers of areas 17, 18 and 19 in the deafferented hemisphere 3, 10 and 30 days after surgery. These results suggest that visual input activates zif‐268 and c‐fos expression and tonically depresses c‐jun expression in the primary visual complex yielding similar levels of c‐jun and c‐fos expression in normal condi...
Cellular Signalling, 2012
The function of the phosphoinositide 5-phosphatase Ship2 was investigated in a new mouse model ex... more The function of the phosphoinositide 5-phosphatase Ship2 was investigated in a new mouse model expressing a germline catalytically-inactive Ship2 Δ/Δ mutant protein. Ship2 Δ/Δ mice were viable with defects in somatic growth and in development of muscle, adipose tissue and female genital tract. Lipid metabolism and insulin secretion were also affected in these mice, but glucose tolerance, insulin sensitivity and insulin-induced PKB phosphorylation were not. We expected that the expression of the catalytically inactive Ship2 protein in PI 3′-kinase-defective p110α D933A/+ mice would counterbalance the phenotypes of parental mice by restoring normal PKB signaling but, for most of the parameters tested, this was not the case. Indeed, often, the Ship2 Δ/Δ phenotype had a dominant effect over the p110α D933A/+ phenotype and, sometimes, there was a surprising additive effect of both mutations. p110α D933A/+ Ship2 Δ/Δ mice still displayed a reduced PKB phosphorylation in response to insulin, compared to wild type mice yet had a normal glucose tolerance and insulin sensitivity, like the Ship2 Δ/Δ mice. Together, our results suggest that the Ship2 Δ/Δ phenotype is not dependent on an overstimulated class I PI 3-kinase-PKB signaling pathway and thus, indirectly, that it may be more dependent on the lack of Ship2-produced phosphatidylinositol 3,4-bisphosphate and derived phosphoinositides.
Anatomy and Embryology, 1992
Pleiotrophin (PTN), also known as HB-GAM, belongs to an emerging cytokine family unrelated to oth... more Pleiotrophin (PTN), also known as HB-GAM, belongs to an emerging cytokine family unrelated to other growth factors. We report here the first comprehensive study using in situ hybridization on the cellular distribution of this new heparin-binding growth factor mRNA in rat tissues. PTN mRNA was developmentally expressed in many-but not all-neuroectodermal and mesodermal lineages, whilst no PTN mRNA was detected in endoderm, ectoderm and trophoblast. PTN mRNA was found in the nervous system throughout development, with a post-natal peak of expression. In the adult nervous system, significant expression persisted in hippocampal CA1 pyramidal neurons and in cortical neurons, but also in different non-neuronal cells types in various locations (olfactory nerve, cerebellar astrocytes, pituicytes, Schwann cells surrounding the neurons in sensory ganglia). PTN mRNA was also found during development in the mesenchyme of lung, gut, kidney and reproductive tract, in bone and cartilage progenitors, in dental pulp, in myoblasts, and in several other sites. Expression was differently regulated in each location, but usually faded around birth. In the adult, PTN mRNA was still present in the meninges, the iris, the Leydig cells of the testis and in the uterus. PTN mRNA was also strongly expressed in the basal layers of the tongue epithelium, which is the only epithelium and ectodermal derivative to express PTN mRNA, and this only after birth. PTN is known to be a growth factor for perinatal brain neurons and a mitogen for fibroblasts in vitro. Recently, trophic effects on epithelial cells and a role as a turnout growth factor have been reported. The mechanisms of regulation and the functions of PTN are however still uncertain. Its expression pattern during development suggests important roles in growth and differentiation. Moreover, the presence of PTN mRNA in several adult tissues and the up-regulation of PTN mRNA expression in the gravid uterus indicate that PTN also has physiological functions during adulthood.
Acta Neuropathologica, 1988
Using immunohistochemistry, well-preserved neuronal cell bodies and fibres containing neuropeptid... more Using immunohistochemistry, well-preserved neuronal cell bodies and fibres containing neuropeptide Y, somatostatin, and cholecystokinin immunoreactivity have been identified in all seven supratentorial anaplastic astrocytomas studied. These neurones have been shown not only on the edge but also in the depth of the neoplastic tissue. These neuropeptides were not present in 18 other intracranial tumours (3 astrocytomas, 1 subependymoma, 8 glioblastoma multiformes, 1 meningioma, and 5 metastases). In all 25 intracranial tumours studied, no immunoreactivity was found for vasoactive intestinal polypeptide, substance P, methionine-enkephalin, leucine-enkephalin, synenkephalin, neurophysin I-II, and corticotropin releasing factor.
European Journal of Neuroscience, 1998
DARPP-32 is a cyclic adenosine monophosphate-regulated inhibitor of protein phosphatase 1, highly... more DARPP-32 is a cyclic adenosine monophosphate-regulated inhibitor of protein phosphatase 1, highly enriched in striatonigral neurons. Stimulation of dopamine D 1 receptors increases phosphorylation of DARPP-32, whereas glutamate acting on N-methyl-D-aspartate receptors induces its dephosphorylation. Yet, to date, there is little direct evidence for the function of DARPP-32 in striatal neurons. Using a whole cell patch-clamp technique, we have studied the role of DARPP-32 in the regulation of voltage-gated sodium channels in rat striatal neurons maintained in primary culture. Injection of phospho-DARPP-32, but not of the unphosphorylated form, reduced the sodium current amplitude. This effect was similar to those induced by okadaic acid, with which there was no additivity and by tautomycin. Our results indicate that, in striatal neurons, sodium channels are under dynamic control by phosphorylation/dephosphorylation, and that phospho-DARPP-32 reduces sodium current by stabilizing a phosphorylated state of the channel or an associated regulatory protein. We propose that the DARPP-32-mediated modulation of sodium channels, via inhibition of phosphatase 1, contributes to the regulation of these channels by D 1 receptors and other neurotransmitters which influence the state of phosphorylation of DARPP-32. Additional actions of dopamine receptors have also been reported (see for review Lledo et al., 1994), including direct inhibition of Ca 2ϩ channels (Lledo et al., 1992), stimulation of voltage-dependent
Journal of neural transmission. Supplementum, 1991
Neuropeptide and neurotransmitter plasticity has been demonstrated in the central nervous system.... more Neuropeptide and neurotransmitter plasticity has been demonstrated in the central nervous system. Modifications of their synthesis occur following receptor blockade or deafferentiation by surgical lesions. This concept should provid answers to some remaining open questions in human pathology especially in degenerative diseases of the basal ganglia. In a severely atrophied striatum we observed a selective increase in the number of detectable striatal substance P and met-enkephalin neurones which exhibited a striking increase in the intensity of labelling. This increase, instead of the well established reduction of substance P and enkephalins in the atrophied striatum of Huntington's disease, could explain the absence of choreoathetosis which was replaced by rigidity and bradykinesia in the patient. The absence of choreoathetosis, despite severe striatal atrophy, is described in several basal ganglia diseases and could also be related to neurotransmitter or neuropeptide plasticity...
The Journal of Neuroscience, 2003
Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in t... more Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recordedin vivothrough unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mmof the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restore t...
Advances in Experimental Medicine and Biology
ABSTRACT
Bulletin et mémoires de l'Académie royale de médecine de Belgique, 2009
The striatum, the first relay of the basal ganglia system, is critically involved in motor functi... more The striatum, the first relay of the basal ganglia system, is critically involved in motor functions and motivational processes. The dorsal striatum is central to the motor control and motor learning and the ventral striatum or nucleus accumbens is essential for motivation, the reward system and reinforcement by drugs. This system is dysfunctional in movement disorders such as Parkinson's disease and Huntington's disease and in psychiatric disorders including drug addiction. The striatum consists of two populations of neurons projecting at the origin of two distinct paths in the circuit of basal ganglia, and of different populations of interneurons. These two populations of efferent neurons, striatopallidal and striatonigral neurons, are characterized by their projection sites and their differential expression in dopamine receptors and neuropeptides. Their roles in motor control and motivational processes and in the mechanisms of neuroadaptation in the system's pathologi...
Progress in brain research, 2005
Calcium binding proteins, such as calretinin, are abundantly expressed in distinctive patterns in... more Calcium binding proteins, such as calretinin, are abundantly expressed in distinctive patterns in the central nervous system but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin deficient mice exhibit dramatic alterations in motor coordination and in Purkinje cell firing recorded in vivo through unknown mechanisms. In the present paper, we review the results obtained with the patch clamp recording techniques in acute slice preparation. This data allow us to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mM of t...
Frontiers in Molecular Neuroscience, 2012
Calcium binding proteins, such as parvalbumin (PV), are abundantly expressed in distinctive patte... more Calcium binding proteins, such as parvalbumin (PV), are abundantly expressed in distinctive patterns in the central nervous system but their physiological function remains poorly understood. Notably, at the level of the striatum, where PV is only expressed in the fast-spiking (FS) interneurons. FS interneurons form an inhibitory network modulating the output of the striatum by synchronizing medium-sized spiny neurons (MSN). So far the existing conductance-based computational models for FS neurons did not allow the study of the coupling between PV concentration and electrical activity. In the present paper, we propose a new mathematical model for the striatal FS interneurons that includes apamin-sensitive small conductance Ca 2+-dependent K + channels (SK) and the presence of a calcium buffer. Our results show that a variation in the concentration of PV can modulate substantially the intrinsic excitability of the FS interneurons and therefore may be involved in the information processing at the striatal level.