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Biomedical subjects

C Berndt

Publications and source records attributed to C Berndt.

27 records · Page 2Linked to original sources

Long-term effects of postnatal hypoxia and flunarizine on the dopaminergic system.

Long-term changes of learning behavior and of the striatal dopaminergic system were observed in a rat model of early postnatal hypoxia. Striatal dopamine (DA) concentration, K(+)-stimulated DA release from slices, and DA uptake into crude synaptosomal preparations (S1 fractions) were used as markers of the striatal DAergic system. Active avoidance learning was tested as behavioral criterion. Cyclodextrin and flunarizine were found to produce long-term effects on the DAergic system in control animals. While cyclodextrin normalized hypoxia-induced effects in DA release, flunarizine prevented those in DA uptake and improved avoidance learning.

3,4-Dihydroxyphenylacetic Acid↗

Effects of postnatal ganglioside administration and hypoxia-exposure on the dopamine release from striatal slices, the behaviour and the ganglioside pattern of 2-3 months old rats.

Neonatal rats were injected with a mixture of bovine brain gangliosides (30 mg/kg body weight, s.c.) immediately before the exposure to hypoxia (pO2 = 10 kPa, 10 hrs daily) from the 2nd to the 11th day of life. At the age of 2-3 months the potential protective or restitutive effect of gangliosides on the radiolabelled dopamine release from striatal slices and on the conditioned avoidance learning was studied. No change in the content and the pattern of gangliosides of the rat striata was found after exposure to hypoxia and ganglioside administration, respectively. Both hypoxia exposure and ganglioside treatment of controls increased the dopamine release whereas hypoxic animals treated with gangliosides showed a diminished release. Hypoxia-induced impaired conditioned avoidance learning was improved by ganglioside treatment. The changed release of dopamine and the altered behavioural performance after ganglioside treatment alone indicate the necessity of a very cautious application of gangliosides to the developing brain.

Aging↗

Lasting effects of postnatal hypoxia and saline injection on the striatal dopamine transport and their modification by gangliosides.

Hypobaric hypoxia (10 h daily, pO2 10 kPa) and saline administration (2.5 microliters/g body wt) from the 2nd till the 11th day of life both induced a long-lasting increase of the low-affinity dopamine (DA) uptake capacity in S1-fractions of the rat striatum. Additionally, the potassium-stimulated DA release was enhanced in adult control rats postnatally injected with saline. The administration of a mixture of bovine brain gangliosides (30 micrograms/g body wt) was found to prevent these effects. However, the kinetic constants of the DA uptake of hypoxic rats treated with gangliosides were reduced in comparison to untreated controls. Thus, the effects of gangliosides appear to differ between hypoxic and control conditions. The modification of the dopaminergic activity during brain development is discussed as a possible mechanism of the preventive effects of gangliosides against long-term cerebral dysfunctions following hypoxia or stress.

Animals↗

Kinetic evidence that the sodium-dependent high-affinity and the sodium-independent low-affinity dopamine uptake are mediated by one carrier.

In synaptosomes of the rat striatum the dopamine uptake was measured in a concentration range of 0.03 microM to 100 microM. In the presence of sodium the uptake exhibited a non-Michaelis-Menten kinetics and in a sodium-free medium the uptake kinetics was sigmoid. According to these findings a novel model for the dopamine uptake is proposed. Its main assumption is one carrier with two dopamine binding sites.

Animals↗

[The epidemiology of wedge shaped defects].

23% of a nonselected group of patients showed wedge shaped defects (9-10 of them per person). The number of teeth with these cervical erosions increases with age. Small accumulation of plaque was found. 65% of the patients with wedge shaped defects had parafunctions and 70% had a chronic pain. A complex of causes underlies the wedge shaped defects. A causal relation appears to exist between wedge shaped defects, occlusal disharmony, parafunctions and strong psychological tension of patients.

Adolescent↗

[Are free oxygen radicals involved in the formation of changes caused by hypoxia in the neurotransmission of dopamine in the striatum of rats?].

The effects of the oxygen radical generating system hypoxanthine (HX)/xanthine oxidase (XO) on the [3 H]--dopamine uptake, the TBARS- and thiol content in striatal synaptosomes of adult rats were examined. Preincubation of synaptosomes with 20 mU XO/0.25 mM HX diminished the dopamine uptake and oxidized thiol groups of synaptosomes. Under these conditions no increase of TBARS, an indicator of lipid peroxidation, was observed. We concluded that in the used hypoxia model free radical mediated damage does not occur.

Animals↗

Increased low affinity dopamine uptake in rat striatum after hypobaric hypoxia.

The influence of a hypobaric hypoxia on the dopamine uptake was studied in rat striatum using a concentration range of dopamine from 30 nM to 0.1 mM. Uptake kinetics were calculated by a non-linear regression computer procedure assuming one carrier protein with two binding sites and negative cooperativity. Hypoxia most prominently affected the low affinity uptake site2; a marked increase of Vmax2 was always obtained. This effect seems to be related to the degree of hypoxia and persists for 10 hours at least. For the high affinity uptake site1, a transient decrease of the Vmax1 was apparent but this effect was less reproducible than the alterations of the low affinity uptake site2. These findings are discussed in the context of increased neuronal dopamine release after oxygen deprivation both in vivo and in vitro.

Animals↗

Postnatal administration of L-dopa normalizes hypoxia-induced long-term changes in dopamine release from striatum slices and in avoidance learning.

Newborn rats exposed to a mild chronic postnatal hypoxia always displayed at the age of 2-3 months an increased fractional efflux rate of dopamine (DA) from striatum slices combined with a decreased capacity for learning and retention. The protective effect of the administration of L-DOPA on these long-term changes was tested by the injection of L-DOPA 5-30 min prior to the beginning of daily exposure to hypoxia. L-DOPA administration during postnatal hypoxia prevents in a dose dependent manner the long-term effects of postnatal hypoxia as described. This finding supports the hypothesis that long-term changes in DA release and in behaviour due to early postnatal hypoxia may be brought about by changes in the DA-metabolism during a critical period of development.

Animals↗

Hypoxia induces different responses of striatal high- and low- affinity dopamine uptake sites.

The dopamine (DA) uptake over a concentration range from 0.03 to 100 microM was studied in S1 fractions of the rat striatum prepared from control rats and those exposed for 14 h to hypobaric hypoxia. The uptake exhibited non-Michaelis-Menten kinetics, which were evaluated by applying an equation assuming two transport sites. The high-affinity uptake site was characterized by an apparent Michaelis-Menten constant of 0.47 microM and an apparent maximal transport rate of 113 pmol/mg protein/30 s. The respective constants of the low-affinity uptake site were 52.8 microM and 1490 pmol/mg protein/30 s. One hour after hypoxia kinetic constants of the high-affinity uptake were unchanged but the maximal transport rate of the low-affinity uptake was increased by 50%. The elevated low-affinity uptake capacity may represent a means of adaptation to hypoxia allowing a faster removal of high extracellular concentrations of DA.

Animals↗