Biomedical subjects

A Marburger

Publications and source records attributed to A Marburger.

8 recordsLinked to original sources

PubMed2001

Dopaminergic mRNA expression in the intact substantia nigra of unilaterally 6-OHDA-lesioned and grafted rats: an in situ hybridization study.

The present study was performed to investigate the influence of intrastriatal fetal mesencephalic grafts on dopaminergic mRNA expression in the non-lesioned substantia nigra pars compacta of unilaterally 6-hydroxydopamine-lesioned rats. The expression of dopamine transporter mRNA, synaptic vesicular monoamine transporter mRNA and tyrosine hydroxylase mRNA was assessed in adjacent cryostat sections using in situ hybridization. Rotational behavior induced by apomorphine and amphetamine as well as hybridization of striatal sections cut at the grafting coordinates were used to prove the functional recovery and the presence of grafted cells, respectively. After grafting, the number of rotations was decreased and hybridization signals overlying cells in the grafted striatum were detected. Mean grain densities overlying labeled neurons in the substantia nigra pars compacta of grafted rats were compared to those of shamgrafted rats and revealed differential expression of dopamine transporter mRNA, whereas synaptic vesicular monoamine transporter mRNA and tyrosine hydroxylase mRNA expression showed no difference. The results will be discussed in relation to previous in vitro and in vivo studies suggesting a reduction of functional dopamine transporter molecules in the contralateral striatum.

Animals↗

PubMed2001

The development of dopamine overflow from foetal nigral grafts in the intact rat striatum and their influence on contralateral striatal dopamine overflow.

In this study, cell suspensions of foetal rat ventral mesencephalic dopaminergic tissue were grafted to the intact (non-lesioned) striatum of adult rats. Differential pulse voltammetry at carbon-fibre micro electrodes (12 microm diameter) was employed to first, monitor the development of dopamine overflow over a 20 week period within the grafts and secondly, their influence on contralateral striatal dopamine overflow. At 8 and 20 weeks, animals were pre-treated with pargyline and both striata were monitored for dopamine overflow for 90 min following d-amphetamine administration. Amphetamine led to a significant increase in dopamine overflow in both the grafted striatum and the contralateral striatum. The time course of dopamine overflow in both the grafted striatum and the striatum contralateral to the graft was similar in all groups of animals. Although the actual concentration of dopamine measured in 20 week old grafts was more (approximately 21%) than that measured in 8 week old grafts, there was no significant difference between the two time points. The concentration of dopamine measured in the striatum contralateral to 8 week old grafts was significantly lower (approximately 43%) than that measured in the striatum of a normal control rats. There was no significant difference between the concentration of dopamine measured in the striatum contralateral to 20 week old grafts and normal control rats. In conclusion, dopamine overflow from a ventral mesencephalic graft does not change significantly between 8 and 20 weeks following grafting. However, the grafted tissue causes a decrease of d-amphetamine-induced dopamine overflow in the contralateral side 8 weeks following grafting, which is restored 12 weeks later.

Animals↗

PubMed2000

Comparison by microdialysis of striatal L-DOPA after its systemic administration in rats with probes implanted acutely or through a guide cannula.

Different methods of microdialysis probe implantation are utilized according to the purpose and needs of each particular study. However, very few experiments have systematically examined whether these different techniques have an impact on the obtained data. In the present study we examined the influence of two different microdialysis methods - acute probe implantation vs. insertion into a preimplanted guide cannula - on the striatal extracellular availability of systemically administered L-DOPA. Furthermore, we monitored the effects of L-DOPA administration on dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). In rats that received a guide cannula 4 days prior to probe insertion and microdialysis, extracellular L-DOPA concentrations increased to concentrations that were about nine times higher than in rats with acute implantation of a microdialysis probe. Extracellular DOPAC concentrations were also higher in the chronic preparations but dopamine concentrations showed no differences between groups. Our results suggest that the observed differences may be due to inflammatory disruption of the BBB following chronic implantation of a guide cannula.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

High frequency stimulation of the subthalamic nucleus influences striatal dopaminergic metabolism in the naive rat.

High frequency stimulation (HFS) of the subthalamic nucleus (STN) can partially alleviate motor symptoms in patients with Parkinson's disease (PD). However, the mechanism of action of HFS is incompletely understood. We investigated the effect of HFS (130 Hz) and low frequency stimulation (LFS, 20 Hz) of the STN on striatal dopaminergic transmission and metabolism using in vivo microdialysis in anaesthetized and freely moving rats. While LFS had no effect, HFS of the STN produced a delayed, stable and intensity-dependent increase of extracellular dopamine metabolites. Striatal extracellular levels of dopamine and 5-HIAA were not influenced by HFS or LFS in the present experimental paradigm. We conclude that HFS of the STN influences striatal dopaminergic metabolism in naive, nonlesioned rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Unilateral fetal mesencephalic grafts in intact rats reduce amphetamine-induced dopamine release in both striata. An in vivo voltammetric study.

This study investigated amphetamine-induced striatal dopamine release after intraventricular unilateral fetal mesencephalic grafts in otherwise intact rats. Dopamine was monitored in vivo by differential pulse voltammetry. In grafted animals, amphetamine-induced dopamine release was decreased compared to sham-grafted, age-matched controls. This decrease was observed in the grafted as well as in the contralateral striatum five months after intraventricular grafting. There was no measurable effect of the graft on the amphetamine-induced rotational behaviour. Our results exceed former observations reporting decreased amphetamine-induced dopamine release in the contralateral striatum of 6-hydroxydopamine-lesioned and unilaterally-grafted rats which had been attributed to a reduction of dopamine transporters. Furthermore, it was shown that concerning this effect ventral mesencephalic grafts are independent of a previous 6-hydroxydopamine lesion.

Amphetamine↗

PubMed1996

Foetal ventral mesencephalic cell suspension grafts to the 6-hydroxydopamine-lesioned rat reduce the rate of dopamine uptake in the contralateral striatum.

The present study employed fast cyclic voltammetry, at carbon-fibre microelectrodes, to monitor and compare the rate of dopamine uptake in the rat striatum contralateral to (a) the 6-hydroxydopamine (6-OHDA)-lesioned/grafted striatum and (b) the 6-OHDA-lesioned/ sham grafted striatum. Cell suspensions of foetal rat ventral mesencephalic tissue were grafted into the dopamine-depleted striatum of unilaterally 6-OHDA-lesioned rats. Six weeks after grafting, animals with functional, mature grafts were monitored for dopamine elimination in the contralateral striatum following electrical stimulation of the median forebrain bundle, before and after treatment with the dopamine uptake inhibitor GBR 12909. Compared to animals with sham grafts, amphetamine-amplified rotational behaviour was significantly reduced in animals with grafts of foetal ventral mesencephalic tissue. Fast cyclic voltammetric measurements followed by evaluation with the aid of a kinetic model revealed that in grafted animals, the rate of dopamine uptake via the high affinity uptake mechanism, following treatment with GBR 12909, was significantly reduced when compared to sham grafted animals.

Amphetamine↗

PubMed1995

Fetal mesencephalic grafts decrease the rate of dopamine uptake in the non-lesioned striatum of unilaterally 6-OHDA lesioned rats: an in vivo voltammetric study.

In the present study the influence of intraventricular fetal mesencephalic grafts on the elimination rate of extracellular dopamine (DA) in the non-lesioned striatum of previously unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats was investigated. The elimination of DA was measured after electrical stimulation of the medial forebrain bundle in vivo before and after treatment with the high affinity uptake inhibitor GBR 12909 (20 mg/kg i.p.) using fast cyclic voltammetry (FCV). Rotational behavior induced by amphetamine (AMPH, 2 mg/kg i.p.) and tyrosine hydroxylase (TH) immunohistochemistry were used to prove the functional recovery and the ingrowth of the graft, respectively. After grafting, the number of rotations was decreased and TH-positive cells and fibers were found in the grafted striatum. Voltammetric measurements with the aid of a kinetic model revealed a smaller rate constant for the in vivo elimination of extracellular DA in the non-lesioned striatum of grafted rats compared to that of non-grafted controls. This effect was abolished after treatment with GBR 12909. Our results will be discussed in relation to the method used and according to recent investigations of the specific [3H]DA uptake into striatal synaptosomes in vitro. Based on these data we conclude that grafts, placed to the lesioned striatum, reduce the DA uptake rate in the non-lesioned striatum due to the reduction of the number of functional DA transporters.

Analysis of Variance↗

PubMed1995

Grafts modulate dopamine transporters of the non-lesioned striatum.

The effect of intraventricular fetal mesencephalic grafts placed in the previously 6-hydroxydopamine (6-OHDA) lesioned striatum on the kinetics of [3H]dopamine (DA) uptake into striatal synaptosomes prepared from the non-lesioned (contralateral) striatum was studied in rats. Using WIN 35,065 as specific [3H]DA uptake inhibitor, the equilibrium dissociation constant (Km) of [3H]DA uptake into synaptosomes of the non-lesioned (contralateral) striatum did not differ between grafted and nongrafted controls 7 months after grafting. However, the maximal rate of specific [3H]DA uptake (Vmax) was markedly decreased in the non-lesioned striatum of grafted animals. This result indicates that fetal mesencephalic grafts reduce the [3H]DNA uptake in the non-lesioned (contralateral) striatum by reducing the number of functional DA transporters.

Analysis of Variance↗