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Biomedical subjects

A McRae-Degueurce

Publications and source records attributed to A McRae-Degueurce.

At least 19 recordsLinked to original sources

An antibody in the CSF of Parkinson's disease patients disappears following adrenal medulla transplantation.

CSF from Parkinson's disease (PD) patients undergoing autologous transplantation of adrenal medulla tissue into their lateral ventricle was examined for the presence of IgG. CSF from 6 of 7 patients incubated with rat brain tissue reacted immunocytochemically to neuronal cell bodies in the substantia nigra and ventral tegmental region. This reactivity gradually disappeared in the months following transplantation. Five of 6 CSF samples from non-transplanted PD patients also produced this immunocytochemical reactivity whereas 26 non-PD samples were immunonegative. Possible implications to the transplant procedure are discussed.

Adrenal Medulla↗

Implantable microencapsulated dopamine (DA): a new approach for slow-release DA delivery into brain tissue.

Biodegradable controlled-release systems constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional and histochemical observations, indicating that implantation of DA microcapsules into striatal tissue assures a prolonged release of the transmitter in situ. This technology has considerable potential for basic and possibly also clinical research.

Animals↗

Fetal serotoninergic transplants in the fourth ventricle of adult rodents reverse sleep disturbances induced by neonatal administration of 5,7-dihydroxytryptamine.

Rats received a neonatal (at 4 days of age) intracisternal injection of 5,7-dihydroxytryptamine which eliminates serotonin (5-HT) throughout adulthood. Sleep recordings, performed on these rats at adult age, demonstrated significant decreases in paradoxical sleep. Dissociated fetal 5-HT cell suspensions transplanted in the IVth ventricle of these rats restored paradoxical sleep. However, fetal neuronal noradrenergic or cholinergic transplants did not restore paradoxical sleep. These results suggest that paradoxical sleep is directly or indirectly mediated through serotoninergic mechanisms.

5,7-Dihydroxytryptamine↗

Influence of ascending serotonergic pathways on glucose use in the conscious rat brain. I. Effects of electrolytic or neurotoxic lesions of the dorsal and/or median raphé nucleus.

The regional cerebral metabolic effects of manipulations of the central serotonergic pathways are largely unknown. To address this topic, we have examined the consequences of electrolytic lesions of the rostral (median and/or dorsal) raphé nuclei on local cerebral glucose utilization (CMRglu) in the unanaesthetized rat brain. These studies were complemented by comparing control rats to rats that received prior intraventricular administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). CMRglu was determined in 56 neuroanatomically defined regions of the central nervous system in lightly restrained rats, by the quantitative autoradiographic 2-deoxyglucose technique. In all, 6 groups of rats were studied: sham-lesioned rats, rats with electrolytic lesion of the median, dorsal, or both these raphé nuclei; sham-injected and 5,7-DHT pretreated rats. The efficacy of both electrolytic and neurotoxic lesions was verified, in each animal, by neurochemical microassay of 5-hydroxytryptamine and its metabolite in samples of striatum, hippocampus and prefrontal cortex. Chronic interruption of serotonergic transmission was remarkable for the lack of resultant change in CMRglu. In rats that were subjected to electrolytic lesions of both median and dorsal raphé nuclei, discrete and significant decreases in CMRglu were observed in the red nucleus, substantia nigra and inferior olivary nucleus only. The rats subjected to 5,7-DHT treatment displayed no significant changes in CMRglu in all the brain regions analyzed, despite an 80% decrease in the concentrations of endogenous 5-hydroxytryptamine. Thus, it would appear that a viable serotonergic transmission is not a major determinant of integrated functional activity, even in those brain structures that receive rich raphé projections. Two hypotheses are advanced for this lack of change: firstly, the chronic reduction of 5-hydroxytryptamine levels is accompanied by compensatory changes in this or other neurotransmitter systems; secondly, serotonergic neurones may exert a phasic--rather than tonic--influence on glucose use in the mammalian brain.

5,7-Dihydroxytryptamine↗

Immunocytochemical investigations on the presence of neuron-specific antibodies in the CSF of Parkinson's disease cases.

The CSF and sera of 7 patients with Parkinson's disease were investigated immunocytochemically, in order to see if antibodies were present which recognized DA-ergic cell bodies in glutaraldehyde fixed rat brain. In 2 patients a marked labeling of DA-ergic neurons in the substantia nigra was observed, identified by anti-DA antiserum and by 6-OHDA induced degeneration, but also other neurons in the ventral mesencephalon were recognized. The other patients were weakly positive or negative. Sera gave unspecific labelling of all neurons. In one patient the sub-classes of IgG were investigated and found to be of IgG3 (labeling nerve terminals) and of IgG1-2, low affinity type (recognizing perikarya). The epitopes recognized have not been identified, but are unlikely to be DA-like, since blocking experiments and ELISA-tests gave negative results. The possible clinical importance of the results are discussed.

Aged↗

Forebrain and brainstem afferents to the arcuate nucleus in the rat: potential pathways for the modulation of hypophyseal secretions.

Doxorubicin, an anti-oncogenic agent, was used as a retrograde marker to identify arcuate nucleus afferent projections. Injections of this tracer into the arcuate nucleus indicated that the subfornical organ, the organum vasculosum of the lamina terminalis, the nucleus raphe dorsalis and median raphe send projections to the arcuate nucleus. Immunocytochemical procedures were used to demonstrate that the raphe projections to the arcuate nucleus are serotoninergic. This anatomical investigation provides evidence that neural pathways exist between forebrain body fluid and mineral nuclei, mesencephalic serotonin nuclei and the arcuate nuclei.

Afferent Pathways↗

Biochemical and radioautographic evidence for dopaminergic afferents of the locus coeruleus originating in the ventral tegmental area.

The dopamine (DA) content of the locus coeruleus (LC) and the uptake of tritiated DA in the presence of desmethylimipramine into fresh vibratome sections of the LC-area were determined in control rats and in rats whose ventral tegmental area (VTA) had been destroyed by local application of 6-hydroxydopamine (6-OHDA). Destruction of the VTA reduced the DA content and the number of dopaminergic fibers visualized by radioautography in the LC area. This indicates that the DA containing afferents of the LC originate, at least partly, in the VTA.

3,4-Dihydroxyphenylacetic Acid↗

Antibodies in cerebrospinal fluid of some Alzheimer disease patients recognize cholinergic neurons in the rat central nervous system.

The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of patients this is indeed the case. The antibodies reported in this study have the following properties: (i) they recognize neuronal populations and components in the medial septum and spinal motor neurons in rats perfused with a mixture that fixes small neurotransmitter molecules; (ii) adsorption of the patient CSF with staphylococcal protein A-Sepharose and using a polyclonal antiserum against human IgG3 indicates that the immunocytochemical reaction in these brain regions is mainly due to the subclass IgG3; and (iii) the CSF immunocytochemical reaction is blocked by preincubation of the sections with a rabbit anti-acetylcholine antiserum. These results provide evidence that antibodies in the CSF of some, but not all, Alzheimer disease patients recognize acetylcholine-like epitopes in cholinergic neurons in the rat central nervous system.

Acetylcholine↗

One perfusion mixture for immunocytochemical detection of noradrenaline, dopamine, serotonin and acetylcholine in the same rat brain.

A perfusion mixture composed of glutaraldehyde and allyl-alcohol at pH 12 is compatible for the fixation and immunocytochemical detection of noradrenaline, dopamine, serotonin and acetylcholine in the same rodent central nervous system. A technical description of this procedure is provided to facilitate the replication of this immunocytochemical approach with these antibodies.

Acetylcholine↗

Fetal noradrenergic transplants into amine-depleted basal forebrain nuclei restore drinking to angiotensin.

6-Hydroxydopamine-induced catecholamine denervations in the organum vasculosum of the lamina terminalis and the median preoptic nucleus attenuate drinking responses to systemic angiotensin II (ANG II) injections. Transplanting catecholamines in these nuclei using fetal noradrenergic (NE) cell suspension restores ANG II-elicited thirst. These results emphasize the functional importance of NE neuronal systems in nuclei of the anteroventral third ventricle (AV3V) in mediating ANG II-induced drinking behaviors.

Angiotensin II↗

Immunocytochemical detection of acetylcholine in the rat central nervous system.

A specific antibody to acetylcholine was raised and used as a marker for cholinergic neurons in the rat central nervous system. The acetylcholine conjugate was obtained by a two-step immunogen synthesis procedure. An enzyme-linked immunosorbent assay was used to test the specificity and affinity of the antibody in vitro; the results indicated high affinity. A chemical perfusion mixture of allyl alcohol and glutaraldehyde was used to fix the acetylcholine in the nervous tissue. Peroxidase-antiperoxidase immunocytochemistry showed many acetylcholine-immunoreactive cells and fibers in sections from the medial septum region.

Acetylcholine↗

In vivo voltammetric measurement of extracellular 5-hydroxyindoleacetic acid in the denervated striatum after transplantation of mesencephalic raphe neurons.

In vivo differential pulse voltammetry with carbon fiber electrodes was used to monitor extracellular 5-hydroxyindoleacetic acid (5-HIAA) levels in a serotonergic denervated target area, the striatum, before and after transplantation of mesencephalic raphé nuclei into the lateral ventricle in the rat. The amplitude of the electrochemical signal recorded in the striatum on the transplanted side was found to be comparable to that measured in control striatum whereas the signal measured from the contralateral nontransplanted striatum was negligible. These findings suggest that mesencephalic raphé nuclei transplants establish connections with the host tissue.

Animals↗

Anaesthetic and forebrain modulation of raphe-coerulean interactions.

Variations in tyrosine hydroxylase (TH) activity and serotonin (5-HT) content in the rat locus coeruleus were measured four days after lesion of the nucleus raphe centralis superior. Lesions were made under either ether or pentobarbital anaesthesia and, in addition, (under ether) in rats pretreated with atropine or with lesions of the medial septum. Results showed a dissociation between 5-HT reduction and TH induction, differences due to the anaesthetic used, and a possible influence from limbic centres on 5-HT in the LC. These findings are discussed in terms of the apparent complexity of raphe-coerulean interactions.

Anesthesia, General↗

Adult age destruction versus neonatal age destruction of the serotonin system: two models to investigate the survival of serotonin neurons transplanted in adult rats.

Mesencephalic raphe nuclei were transplanted via the cisterna magna in the IVth ventricle of adult rats having received either a neonatal or an adult age destruction of the serotonin system. In neonatally treated rats both serotonin (5-HT) and glial fibrillary acidic protein (GFA) immunocytochemistry showed an absence of survival of 5-HT neurons in the transplants. However, many 5-HT immunoreactive cell bodies and processes were detected in 10-month-old transplants in adult treated animals. These results suggest that recognition processes between the target tissue and the implant may be a prerequisite for the survival of grafted neurons.

Age Factors↗

Serotonin and dopamine afferents to the rat locus coeruleus: a biochemical study after lesioning of the ventral mesencephalic tegmental-A10 region and the raphé dorsalis.

The monoamine levels in the locus coeruleus (LC) were determined by HPLC following specific lesions of the ventral mesencephalic tegmental-A10 regions (VMT-A10) and raphé dorsalis (RD). Only lesions in the VMT-A10 area decreased the dopamine (DA) content, which strongly suggests that the projection from this region to the LC is of dopaminergic nature. Lesions of the RD increased DA metabolism in the LC and provoked significant decreases in the serotonin (5-HT) levels.

Animals↗

Pharmacological investigation on the role of dopamine in the rat locus coeruleus.

The role of dopamine (DA) in the rat locus coeruleus (LC) was investigated by determining the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), DA and noradrenaline (NA) in the LC after pharmacological treatments by pargyline, haloperidol, 6-hydroxydopamine (6-OHDA) and desmethylimipramine (DMI). The DA, DOPAC and NA contents of the LC were determined by high pressure liquid chromatography. Fifteen days after 6-OHDA, the DOPAC and NA levels were reduced by 60%, but they remained constant after 6-OHDA + DMI. Pargyline provoked highly significant increases in DA and NA but reduced DOPAC to non-measurable amounts. haloperidol caused a 54% decrease in the DOPAC levels. Pargyline and haloperidol administered to rats having received 6-OHDA + DMI 15 days before, caused similar effects on DA, DOPAC and NA levels as those in non-treated rats. It is suggested that DOPAC is mainly located in noradrenergic neurons, thus eliminating the possibility of a significant DA cell body population in the rat LC.

3,4-Dihydroxyphenylacetic Acid↗