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J B Gramsbergen

Publications and source records attributed to J B Gramsbergen.

30 records · Page 2Linked to original sources
PubMed1990

Determination of extracellular kynurenic acid in the striatum of unanesthetized rats: effect of aminooxyacetic acid.

Kynurenic acid (KYNA) production from its bioprecursor L-kynurenine (KYN) was assessed in vivo by intrastriatal microdialysis in freely moving rats. In the absence of KYN, the extracellular concentration of KYNA was below the limit of assay sensitivity (i.e. less than 8 pmol/30 microliters). In the presence of KYN (50-2000 microM), KYNA concentration in the dialysate increased continuously to reach steady-state levels after 2h of perfusion. Introduction of the unspecific transaminase inhibitor aminooxyacetic acid (AOAA) through the dialysis probe caused a progressive decrease of extracellular KYNA, which reached dose-dependent minimal levels within 2 h. One mM AOAA caused an almost complete depletion of KYNA in the dialysate. These data demonstrate that extracellular KYNA can be assessed by microdialysis and that AOAA can be used as a tool to examine the neurobiology of KYNA in awake, freely moving animals.

Aminooxyacetic Acid↗
PubMed1990

Kynurenic acid synthesis by human glioma.

Biopsy material from human gliomas obtained during neurosurgery was used to investigate whether pathological human brain tissue is capable of producing kynurenic acid (KYNA), a natural brain metabolite which can act as an antagonist at excitatory amino acid receptors. Upon in vitro exposure to 40, 200 or 1000 microM L-kynurenine, the immediate bioprecursor of KYNA, freshly prepared tissue slices in a dose-dependent fashion produced KYNA which was detected in the incubation medium. De novo synthesized KYNA was identified by several chromatographic procedures. Astrocytomas produced significantly more KYNA than glioblastomas.

Adult↗
PubMed1989

Rat brain slices produce and liberate kynurenic acid upon exposure to L-kynurenine.

The incorporation of L-kynurenine (L-KYN) into kynurenic acid (KYNA) was examined in rat brain slices. KYNA was measured in the slices and in the incubation medium after purification by ion-exchange and HPLC chromatography. In pilot experiments, the formation of KYNA was confirmed by gas chromatography. KYNA was produced stereoselectively from L-KYN, and approximately 90% of the newly synthesized KYNA was recovered from the incubation medium. Intracellular KYNA was not actively retained by the tissue and was lost from the cells upon repeated washes. Thus, regulation of the levels of extracellular KYNA appears to occur at the level of L-KYN uptake and/or kynurenine transaminase, the biosynthetic enzyme of KYNA. KYNA production from L-KYN was linear up to 4 h and reached a plateau at a L-KYN concentration of 250 microM. The process was effectively inhibited by the transaminase inhibitor aminooxyacetic acid (IC50, approximately 25 microM), and showed pronounced regional distribution (hippocampus greater than cortical areas greater than thalamus much greater than cerebellum). The conversion of L-KYN to KYNA was dependent on oxygenation and on the presence of glucose in the incubation medium. Neither deletion of Ca2+ or Mg2+ nor addition of 20 mM Mg2+ had any effect. However, KYNA production was significantly attenuated in the absence of Cl- or in the presence of 50 mM K+ in the incubation medium. In Na+-free medium, the production of KYNA from L-KYN was increased by 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminooxyacetic Acid↗
PubMed1988

Imaging of the degeneration of neurons and their processes in rat or cat brain by 45CaCl2 autoradiography or 55CoCl2 positron emission tomography.

The possibility of using radiolabeled divalent cations to visualize nerve cell degeneration in the brain was investigated after intoxication with neurotoxins. At different survival times after the intracerebral injection of kainic acid or 6-hydroxydopamine, autoradiographs were made from brain sections of rats that had received 45CaCl2 intravenously 24 h before death. Brain sections, adjacent to those used for autoradiography, of the 6-hydroxydopamine-treated rats were used for histofluorescence of catecholamines to check the neurochemical effect of the treatment. These experiments show that radioactive Ca accumulates in brain tissue during a particular phase of degeneration. Not only could degenerating cell bodies be traced by 45Ca autoradiography, but also degenerating nerve terminals in the striato-nigral and nigro-striatal projection systems. In positron emission tomography (PET) studies, 55CoCl2 was used as a marker for Ca2+. Unilateral lesions of the cat forebrain, produced by kainic acid, could be imaged in vivo by PET with 55CoCl2. PET with this radiolabel may provide diagnostic potentials for human neurodegenerative disorders.

Animals↗
PubMed1986

Cerebral cation shifts and amino acids in Huntington's disease.

The cations, calcium, magnesium, sodium, and potassium, putative amino acid transmitters, and total protein contents were assessed in the frontal cortex, putamen, and substantia nigra of Huntington's disease (HD) patients and age-matched nonneurologic control subjects. In the HD frontal cortex and HD substantia nigra, only small increases in sodium levels and decreases in potassium levels were observed, but in the HD putamen there were major cation shifts, suggesting a twofold increase of the extracellular space. In all three brain areas that were investigated, potassium was positively correlated with gamma-aminobutyric acid and in the putamen sodium was negatively correlated with the amino acid. These correlations suggest loss of gamma-aminobutyric acidergic neurons or nerve terminals in these areas. The elevation of sodium in the HD basal ganglia may be visualized in vivo by nuclear magnetic resonance of sodium.

Adult↗
PubMed1986

In vivo labelling and axonal transport of monoamine oxidase in the rat basal ganglia using radioactive pargyline.

The enzyme monoamine oxidase was labelled in the rat striatum or substantia nigra with locally injected radioactive pargyline. The binding was prevented by a pretreatment with non-radioactive pargyline, or with a combination of clorgyline and deprenyl. Most of the MAO labelled with 3H-pargyline was of the B-type, but also some MAO-A was labelled, as shown in rats pretreated with clorgyline or deprenyl separately. Seven days after the injection of (3H)-pargyline into the striatum a significant labelling was observed in the substantia nigra. This labelling was clorgyline sensitive, indicating type A MAO, and was not present when striatal neurons were destroyed with kainic acid. Labelling of the striatum following 3H-pargyline injection into the substantia nigra was also less in kainate intoxicated striata. Damage of nigral dopamine neurons with 6-hydroxydopamine did not influence the distribution of the label. Thus by using 3H-pargyline, specific labelling and axonal transport of type A MAO in striatal neurons projecting to the substantia nigra was demonstrated.

Animals↗
PubMedDate not supplied

A correlative study on hippocampal cation shifts and amino acids and clinico-pathological data in Alzheimer's disease.

Amino acid transmitters and cations were assessed in the frontal cortex and hippocampus of 12 Alzheimer's disease (AD), 4 multi-infarct dementia (MID) patients, and 12 age-matched controls. In the hippocampus, but not in the frontal cortex of AD patients we observed an increase of sodium (Na) and a decrease of potassium (K) and magnesium (Mg) content as compared to controls. Calcium (Ca) was not changed. These cation shifts were highly correlated with glutamate, which was significantly decreased in AD hippocampus. Hippocampal Na and K levels correlated also highly with gamma-aminobutyrate, cholineacetyltransferase and noradrenaline levels in the hippocampus and dementia scores. These results show that Na and K changes are sensitive markers for neurodegenerative processes in AD and suggest a loss of glutamatergic neurons in AD hippocampus.

Aged↗