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M F Chesselet

Publications and source records attributed to M F Chesselet.

At least 73 records · Page 4Linked to original sources
PubMed1991

Preproenkephalin messenger RNA-containing neurons in striatum of patients with symptomatic and presymptomatic Huntington's disease: an in situ hybridization study.

Previous studies have revealed a loss of enkephalin immunoreactivity in the terminals of striatal neurons projecting to the external globus pallidus in patients with early grades of Huntington's disease (HD). To assess the status of the perikarya of striatal enkephalinergic neurons, we performed in situ hybridization histochemistry with a radiolabeled RNA probe complementary to preproenkephalin messenger RNA. We studied postmortem brain tissue of 6 patients with symptomatic HD, 7 control subjects, and 2 presymptomatic carriers of the HD allele. There was a significant reduction in the areal density of striatal neurons expressing preproenkephalin messenger RNA in the patients with symptomatic HD, but the level of labeling in the remaining cells was not altered compared with the control subjects. In the specimens from presymptomatic individuals, there was no reduction of areal density of preproenkephalin messenger RNA-containing neurons in the striatum, despite the fact that loss of enkephalin immunoreactivity in the external globus pallidus had been previously demonstrated in the same brains. The results correlate with the previous demonstration of depleted enkephalin immunoreactive terminals in the external globus pallidus in patients with symptomatic HD. They also suggest that the early loss of enkephalin immunoreactivity observed in the external globus pallidus of presymptomatic carriers of the HD allele is not related to a generalized death of striatal enkephalinergic neurons early in the course of the disease.

Adolescent↗
PubMed1991

Heterogeneous distribution of dopamine D2 receptor mRNA in the rat striatum: a quantitative analysis with in situ hybridization histochemistry.

Dopamine D2 receptor mRNAs have recently been cloned and their gross distribution in the central nervous system described. Quantitative in situ hybridization histochemistry with a cRNA probe complementary to the mRNAs encoding approximately 70% of the third intracellular loop of the rat D2 receptor was performed on sections of rat brain to determine whether differences previously observed in the density of ligand binding sites in subregions of the striatum were related to differences in mRNA levels. Film autoradiographic analysis demonstrated 30% more hybridization signal in the lateral compared to the medial caudate-putamen, a distribution parallel to that of binding of ligands specific for the D2 receptor. Inspection at the cellular level using emulsion autoradiography also indicated a differential distribution of the D2 receptor mRNA. Fewer positively labelled cells, as well as fewer silver grains per cell, were seen in the medial compared to the lateral half of the striatum. This suggests that the gradient seen in autoradiographic studies of the distribution of D2 receptors is related both to regional differences in D2 mRNA levels and to the density of cells expressing the receptor. In addition, the distribution of cells expressing D2 receptor mRNA in the extrastriosomal matrix was compared to that in striosomes identified by the presence of a high density of 3H-naloxone binding sites. Labelled cells were mainly found in the matrix (3H-naloxone binding-poor) but were also seen in striosomes (3H-naloxone binding-rich). The results suggest that differences in levels of D2 binding sites in subregions of the striatum are related to differences in the level of expression of this receptor in intrinsic striatal neurons, suggesting differential regulation of dopamine D2 receptor gene expression in topographically distinct striatal neurons.

Animals↗
PubMed1991

Distribution of glutamic acid decarboxylase (Mr 67,000) in the basal ganglia of the rat: an immunohistochemical study with a selective cDNA-generated polyclonal antibody.

Distinct isoforms of glutamic acid decarboxylase, the synthetic enzyme for GABA, exist in brain. Their distribution at the cellular level is not known, because previous studies have been confounded by the lack of monospecificity of available antibodies. We have examined the distribution of glutamic acid decarboxylase (Mr 67,000; GAD67) in the basal ganglia of the rat with a polyclonal antibody generated against the protein expressed in bacteria transformed with the corresponding cDNA. This antibody, which is directed against a portion of GAD67 non homologous to other known glutamic acid decarboxylase isoforms, selectively recognizes GAD67 on western blots. We show that GAD67 is present to various degree in all types of GABAergic neurons previously described in these regions. In contrast with results obtained with non-selective antibodies for glutamic acid decarboxylase, GAD67-positive neuronal cell bodies were readily detected in sections of the striatum, pallidum and substantia nigra in the absence of colchicine treatment. Modifications in the immunohistochemical procedure favoured staining of glutamic acid decarboxylase-positive fibres with the same antibody, indicating that GAD67 is also present in axon terminals of GABAergic neurons. The results suggest that GAD67 may be involved in GABA synthesis in both cell bodies and axon terminals of all GABAergic neurons of the basal ganglia, but is particularly abundant or accessible in their cell bodies.

Animals↗
PubMed1991

Heterogeneous distribution of the limbic system-associated membrane protein in the caudate nucleus and substantia nigra of the cat.

The limbic system-associated membrane protein is a glycoprotein selectively associated, in the adult, with dendrites and cell bodies of neurons of the limbic system and related brain regions. In the present study, the distribution of the limbic system-associated membrane protein was studied by immunohistochemistry in the caudate nucleus and substantia nigra of the cat to determine how its expression relates to the compartmentalization of these areas. In all areas of the caudate nucleus, the pattern of limbic system-associated membrane protein immunoreactivity was highly heterogeneous, labeling zones that were in register with areas expressing neurochemical markers that classically identify striosomes. The extrastriosomal matrix exhibited low levels of staining. The results show that the limbic system-associated membrane protein is expressed by neurons within the target areas (striosomes) of subsets of limbic afferents (originating mainly from the basolateral nucleus of the amygdala and the prefrontal cortex), whereas regions of the caudate nucleus (extrastriosomal matrix) receiving inputs from other subdivisions of the limbic system, such as the cingulate cortex and the ventral tegmental area, contain relatively low levels of limbic system-associated membrane protein immunoreactivity. Thus the expression of this antigen may reflect the targeting of specific groups of limbic afferents to regions that are intimately associated with distinct components of the limbic system. The presence of limbic system-associated membrane protein in neurons of the substantia nigra pars compacta does not appear to be related to the presence or absence of the protein in their striatal target areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1991

Lesions of the dopaminergic nigrostriatal pathway alter preprosomatostatin messenger RNA levels in the striatum, the entopeduncular nucleus and the lateral hypothalamus of the rat.

The distribution and level of labeling for the messenger RNA encoding preprosomatostatin was studied in the striatum and entopeduncular nucleus of rats with and without a selective destruction of the dopaminergic nigrostriatal pathway. 6-Hydroxydopamine was injected unilaterally in the substantia nigra and the animals were killed 2 or 3 weeks after the lesion. Preprosomatostatin messenger RNA was visualized with a 35S-labeled RNA or DNA probe in frontal cryostat-cut sections by in situ hybridization histochemistry. The number of labeled cells as well as the intensity of labeling overlying each cell were measured on radioautograms developed before saturation of the emulsion. In rats with a 6-hydroxydopamine lesion, the number of labeled cells and the intensity of labeling over each cell were decreased in the striatum ipsilateral to the lesion compared to the contralateral side and to both striata of control rats. In the same sections, the number of cells in the cerebral cortex was lower in the ipsilateral side of the lesion but the difference was only significant in the frontoparietal cortex. In contrast, a massive increase (+300%) in the number of labeled cells and in the intensity of labeling per cell was observed in the entopeduncular nucleus and the adjacent lateral hypothalamus on the side ipsilateral to the lesion when compared to the contralateral side and to control rats. The results suggest that dopamine exerts opposite effects on somatostatin gene expression in neurons of the striatum and the entopeduncular nucleus/lateral hypothalamus, effects which are likely to be of importance for the control of basal ganglia output activity. In addition, the dramatic changes observed in the somatostatinergic neurons of the lateral hypothalamus, an area involved in the control of food and water intake, may be related to some aspects of the symptomatology of Parkinson's disease.

Animals↗
PubMed1991

Differential distribution of somatostatin receptor subtypes in rat brain revealed by newly developed somatostatin analogs.

Somatostatin receptor subtypes were labeled with the somatostatin analogs [125I]CGP 23996 and [125I]MK 678 and the distribution of these receptors in rat brain was investigated using quantitative autoradiographic techniques. [125I]CGP 23996 and [125I]MK 678 specifically label different populations of somatostatin receptors in rat brain. In a number of brain regions striking differences in the distribution of the somatostatin receptor subtypes labeled by each peptide were observed. High levels of binding sites for both [125I]CGP 23996 and [125I]MK 678 were present in the cerebral cortex, CA1 region and subiculum of the hippocampus. In contrast, high levels of [125I]MK 678 binding were found in the dentate gyrus of the hippocampus while few [125I]CGP 23996 binding sites were observed in this brain region. [125I]CGP 23996 binding was detected in the central region of the interpeduncular nucleus whereas the dorsal and lateral subnuclei of this brain area expressed mainly somatostatin receptors with high affinity for MK 678. The locus coeruleus and regions of the superior colliculus and hypothalamus selectively express [125I]MK 678-sensitive somatostatin receptors. Furthermore, limbic structures such as the lateral septum, the nucleus accumbens and ventromedial striatum had much higher levels of [125I]MK 678 binding sites than [125I]CGP 23996 binding sites. Differences in the expression of the somatostatin receptor subtypes were also detected in the substantia nigra. [125I]CGP 23996 binding was present in the pars reticulata but not the pars compacta whereas the reverse distribution for [125I]MK 678 binding sites was observed. The differential distribution of [125I]CGP 23996 and [125I]MK 678 binding sites in rat brain supports the hypothesis that these peptides selectively label different somatostatin receptor subtypes in the central nervous system.

Animals↗
PubMed1990

Heterogeneous distribution of cytochrome oxidase activity in the rat substantia nigra: correlation with tyrosine hydroxylase and dynorphin immunoreactivities.

Cytochrome oxidase (COase) activity, an endogenous marker of neuronal activity, was examined in the substantia nigra of the adult rat at the light-microscopic level. In addition, the pattern of histochemical staining observed for COase activity was correlated with immunohistochemistry for tyrosine hydroxylase (a marker of dopaminergic neurons) and for dynorphin (a peptide present in afferents from the striatum). Differential oxidative metabolic activity was revealed in subregions of the substantia nigra by COase histochemistry. Neurons of the substantia nigra pars compacta (SNc), ventral tegmental area, and ventrally displaced dopaminergic neurons were characterized by little or no staining for COase. In contrast, the substantia nigra pars reticulata (SNr) possessed a heterogeneous distribution of COase activity that was characterized by denser staining in the ventrolateral than the dorsomedial part of the nucleus throughout its rostrocaudal extent, with the exception of the most rostral levels. This pattern of COase activity was inversely correlated with the density of ventrally descending tyrosine hydroxylase-positive dendrites arising from the medial portion of the SNc, as well as with the density of dynorphin immunoreactivity. The results suggest that the SNc and SNr possess distinct levels of oxidative metabolic activity. Furthermore, within the SNr itself, different levels of COase activity characterize subpopulations of neurons which may be differentially regulated by both striatal and dopaminergic influences.

Animals↗
PubMed1990

Increased glutamic acid decarboxylase (GAD) mRNA and GAD activity in cerebellar Purkinje cells following lesion-induced increases in cell firing.

Lesions of the inferior olive-climbing fiber projection to the cerebellar Purkinje cell were produced in adult rats using the neurotoxin 3-acetylpyridine. At 7 days post-lesion, glutamic acid decarboxylase (GAD) activity in Purkinje cell axons terminating in the lateral division of the deep cerebellar nucleus was significantly increased (+58%) above control levels. GAD mRNA levels in Purkinje cell bodies from the same animals were measured by in situ hybridization histochemistry using a radiolabeled cRNA probe for GAD mRNA. GAD mRNA was significantly elevated (+42%) above control at 7 days post-lesion. Because lesions of the climbing fiber system increase Purkinje cell firing rates, the results suggest that increased Purkinje cell activity induces transcription of GAD mRNA, which in turn results in increased GAD availability in Purkinje cell terminals.

Animals↗
PubMed1990

Amygdalonigral pathway: an anterograde study in the rat with Phaseolus vulgaris leucoagglutinin (PHA-L).

The projection from the central nucleus of the amygdala to the substantia nigra was labeled by injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into different subregions of the nucleus. A sparse projection of labeled bouton-like swellings was observed in the rostral, medial substantia nigra pars compacta and ventral tegmental area from all subregions of the central nucleus of the amygdala that were injected. A dense projection of labeled axons and bouton-like swellings was observed in the lateral part of the substantia nigra pars compacta and pars lateralis when the injection site included the dorsal and rostral central nucleus. Heavy labeling was also seen in the lateral retrorubral field in these cases. In no instances were labeled terminals observed in the substantia nigra pars reticulata. The same pattern of labeling in the lateral substantia nigra and retrorubral field was seen after injections rostral to the central nucleus or dorsal and medial to it in the sublenticular region. The results suggest that the amygdalonigral pathway contributes to the innervation of extensive areas of the substantia nigra pars compacta. The major component of the pathway, however, projects only to a subregion of the substantia nigra. The origin of this pathway is confined to a discrete region of the dorsal central nucleus of the amygdala but extends rostrally into an area that is part of the "extended amygdala."

Amygdala↗
PubMed1990

Differential effects of chronic treatment with haloperidol and clozapine on the level of preprosomatostatin mRNA in the striatum, nucleus accumbens, and frontal cortex of the rat.

1. The goal of this work was to determine the effects of typical and atypical neuroleptics on the level of preprosomatostatin messenger RNA (mRNA) in regions of the rat brain innervated by dopaminergic neurons. 2. Quantitative in situ hybridization histochemistry was used to measure the levels of mRNA encoding preprosomatostatin in neurons of the striatum, the nucleus accumbens, and the medial and lateral agranular areas of the frontal cortex in adult rats treated with either haloperidol or clozapine. 3. In untreated animals, the density of neurons containing preprosomatostatin mRNA was higher in the nucleus accumbens than in the striatum and frontal cortex. The intensity of labeling per neuron, however, was higher in the striatum than in the two other areas examined, suggesting that the expression of preprosomatostatin mRNA is differentially regulated in these brain regions. Chronic administration of haloperidol (1 mg/kg for 28 days) induced a significant decrease in the labeling for preprosomatostatin mRNA in neurons of the nucleus accumbens, frontal cortex, and medial but not lateral striatum. Treatment with clozapine (20 mg/kg for 28 days) increased the levels of preprosomatostatin mRNA in the nucleus accumbens but not in the striatum or the frontal cortex. 4. These results support a role for dopamine in the regulation of central somatostatinergic neurons. The differences in the effects of haloperidol, a neuroleptic which induces extrapyramidal side effects, and clozapine, which does not, suggest that somatostatinergic neurons may play an important role in the regulation of motor behavior.

Animals↗
PubMed1990

Ischemic damage in the striatum of adult gerbils: relative sparing of somatostatinergic and cholinergic interneurons contrasts with loss of efferent neurons.

The pattern of ischemia-induced cell death was examined with histochemical methods in the striatum of adult gerbils 4 and 7 days after transient forebrain ischemia. The results showed a massive loss of immunoreactivity to enkephalin and tachykinins, peptides present in striatal efferent neurons. In contrast, neurons expressing acetylcholinesterase activity, or choline acetyltransferase immunoreactivity, as well as neurons immunoreactive for somatostatin, were relatively preserved in areas of severe neuronal loss. The selective vulnerability of subpopulations of striatal neurons to transient ischemia in the adult is similar to that observed in the neonate and after local injections of agonists of N-methyl-D-aspartate receptors, but not of agonists of other glutamate receptor subtypes. It also presents striking similarities to the pattern of neuronal death observed in Huntington's disease. The results further support a role for overstimulation of a subtype of excitatory amino acid receptor in ischemia-induced cell death and show that the selective sparing of subpopulations of striatal interneurons after ischemic injury is not related to immaturity of these neurons but also occurs in the adult.

Acetylcholinesterase↗
PubMed1990

Expression of beta-preprotachykinin mRNA and tachykinins in rat dorsal root ganglion cells following peripheral or central axotomy.

The changes in gene expression and protein synthesis induced in neurons by axotomy usually lead to increased production of axon constituents and decreased production of molecules related to neurotransmission. Exceptions to this generalization occur, however, and it is unclear whether the injury itself changes the pattern of synthesis or whether individual mechanisms regulate the synthesis of the various axonal components. We used in situ hybridization histochemistry and immunocytochemistry to compare the changes in L4 and L5 rat dorsal root ganglion neuron levels of preprotachykinin mRNA and tachykinin peptides caused by sciatic nerve injury with those caused by dorsal root injury. Both lesions elicit regeneration, although only the axotomized peripheral processes re-establish functional contact with their targets. In the contralateral, intact dorsal root ganglia approximately 17% of neurons contained detectable levels of both mRNAs and peptides. Sciatic nerve section decreased by 70% the number of neurons labeled for preprotachykinin mRNA at three days post-operatively. Not all cells in the ganglion are axotomized by the sciatic nerve lesion; grain counts over the cells spared by the lesion showed an increased level of labeling, possibly a result of collateral sprouting by these spared cells. By two weeks, the number of cells labeled for preprotachykinin mRNA had decreased to 80% of control levels. The numbers of neurons labeled for tachykinin peptides decreased more slowly and reached approximately 50% of control numbers at two weeks. By six months post-operatively, when regeneration is largely complete, the number of neurons containing both mRNAs and peptides returned to normal. In contrast, dorsal root section did not elicit a decrease in the number of neurons labeled either for the mRNAs or the peptides at any of the post-operative intervals examined. These results indicate that axotomy is not the stimulus that elicits changes in the expression of genes coding for tachykinins. Evidence is considered indicating that interruption of the supply of peripherally derived nerve growth factor may be responsible for the changes in gene expression for tachykinins after axotomy.

Animals↗
PubMed1990

Post-translation modifications of neural cell surface molecules.

Neural cells seem to express a relatively low number of adhesion molecules at their surface. The hypothesis of cell surface modulation postulates that a repertoire of specificities and binding affinities might result from alteration over time of the amount, distribution or chemical properties of a particular kind of molecules. We are describing two post-translational modifications; glycosylation and glypiation; which affect the neural cell adhesive molecule (N-CAM). We produced a monoclonal antibody recognizing only the highly sialyled of N-CAM and reported some of its applications. We also showed that N-CAM-120 is anchored to the membranes via a complex glycane-phosphatidylinositol.

Animals↗
PubMed1989

Characterization of striatal neurons expressing high levels of glutamic acid decarboxylase messenger RNA.

Two types of labelled cells are detected in sections of rat and mouse striata processed for in situ hybridization histochemistry with 35S-radiolabelled RNA probes complementary to the messenger RNA (mRNA) encoding glutamic acid decarboxylase (GAD), the synthesis enzyme for gamma-aminobutyric acid (GABA): numerous lightly, and fewer very densely labelled neurons. In order to determine whether the densely labelled cells correspond to the striatal somatostatinergic neurons with which they share morphological characteristics, the presence of GAD mRNA was examined in brain sections processed successively for dihydronicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry, a marker of striatal somatostatinergic neurons, and in situ hybridization histochemistry. In addition, the distribution of GABAergic interneurons was analyzed with regard to striatal compartments (striosomes) indicated by patches of dense opiate binding sites. The results show that NADPH diaphorase activity and GAD mRNA do not co-exist in striatal neurons. Furthermore, in contrast to the somatostatinergic neurons which are almost exclusively located in the extrastriosomal matrix, densely labelled GAD cells were present both in the striosomes and the matrix, further suggesting that GABAergic and somatostatinergic neurons form two distinct interneuronal systems in the striatum of rats and mice.

Animals↗
PubMed1989

Regional differences in substance P-like immunoreactivity in the striatum correlate with levels of pre-protachykinin mRNA.

The distribution of neurons containing the messenger RNA encoding preprotachykinin, the precursor of the neuropeptides substance P and K, was examined in the striatum of the rat. The large majority of cells densely labelled by in situ hybridization histochemistry (using a 35S-radiolabelled RNA probe complementary of the beta-preprotachykinin mRNA) were located within the boundaries of areas of dense [3H]naloxone binding which delineate the striosomes, a striatal compartment distinct from the surrounding matrix with respect to its inputs, outputs and neurochemical content. In view of previous immunohistochemical data, the results suggest that tachykinin-containing neurons of the striosomes have a higher rate of tachykinin synthesis than those neurons located in the surrounding striatal matrix.

Animals↗
PubMed1989

Regional distribution and regulation of preprosomatostatin messenger RNA in the striatum, as revealed by in situ hybridization histochemistry.

Quantitative in situ hybridization was used to examine the regional distribution of preprosomatostatin messenger RNA (PPSOM mRNA) in the dorsal striatum (caudo-putamen) of the mouse. In addition, because mesencephalic dopaminergic neurons project to the striatum where they play a role in the regulation of peptide-containing neurons, the effect of dopamine receptor blockade on the levels of striatal PPSOM mRNA was determined. Sagittal brain sections from male Swiss Webster mice were processed for in situ hybridization histochemistry using an 35S-radiolabelled RNA probe in order to quantify levels of PPSOM mRNA in individual neurons of the dorsal caudo-putamen using light microscopy and computer-assisted grain analysis. In control animals, individual neurons of the dorsolateral caudo-putamen had higher levels of PPSOM mRNA than did those of the medial part of the structure. Treated mice were injected with fluphenazine-N-mustard (FNM), an antagonist which, at the dose used (4 mumol/kg), irreversibly blocks dopamine D2 but not D1 receptors in the mouse striatum. FNM treatment (for 2 days, twice a day) produced an increase in striatal dopamine turnover and a decrease in PPSOM mRNA levels in the lateral, but not the medial striatum. The results indicate that there is a lateral to medial gradient in the levels of PPSOM mRNA per individual neuron in the dorsal caudo-putamen of control animals, which is abolished by FNM treatment. This suggests that intrinsic striatal somatostatinergic neurons are differentially regulated by dopamine, depending on their lateromedial location within the striatum.

Animals↗