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H P Klemm

Publications and source records attributed to H P Klemm.

17 recordsLinked to original sources

Locus coeruleus - cerebellum: interaction during development.

The presentation describes a combined morphological and biochemical analysis of the developmental interaction between the locus coeruleus (LC) and the cerebellum of rats, which receives an afferent innervation from the LC. The LC neurons are among the first CNS neurons to arise during ontogeny. They establish axonal connections to their target areas while migrating into their nuclear area, where they collect around E17. Their perikaryal development proceeds through the well-known stages of neuronal differentiation, Nissl body formation as a sign of synaptic connectivity appearing for the first time on E18. However, changes in the LC-perikarya are taking place in early postnatal stages. Perikaryal volume increases to reach a transitory maximum of 150% of the adult value on P15. Ultrastructurally, a dissolution of Nissl bodies and an increase in the number of polyribosomes are seen during this developmental period, reminiscent of perikaryal changes during the axon reaction. Later, the organization of ribonucleoproteins into Nissl bodies is re-established. NA axons are demonstrable in the cerebellar anlage for the first time on E17. They increase rapidly in number and organization during cerebellar development as shown by catecholamines histofluorescence. Quantitative measurements of cerebellar high-affinity uptake for NA show that a peak of NA innervation is reached on P10, which amounts to about 250% of the adult value. This hyper-innervation is transitory and declines to adult values on P20. The period of cerebellar NA hyperinnervation corresponds to the perikaryal changes in volume and ultrastructure of LC neurons. The phenomenon of transitory hyperinnervation of a target area is discussed with respect to the establishment of axonal connections during normal development and in regeneration.

Animals↗

Serotonin neurotoxins: recent advances in the mode of administration and molecular mechanism of action.

1. Slow infusion of 5,7-DHT into the left lateral ventricle of nomifensine pretreated, pentobarbitone anaesthetized rats produces moderate, asymmetric regional forebrain 5-HT depletions 24 h after the injection; rapid pulse injection of 5,7-DHT results in more extensive and almost symmetric 5-HT reductions. By the eighth day, both injection procedures cause a comparable pattern of 5-HT depletion throughout the CNS. RAdioactivity distribution patterns (following 14C-5,7-DHT) correlate with the characteristics of 5-HT depletions. The type of anaesthetic used (pentobarbitone; pentobarbitone plus ketamine; ether) has little, if any, influence on the long-term 5-HT reductions in the rat CNS. 2. In forebrain regions, near the ventricle, nomifensine does not totally protect catecholamine fibre systems when pentobarbitone is used as the anaesthetic. However, optimum selectivity is provided by a combination of DMI and nomifensine in animals anaesthetized with a combination of pentobarbitone and ketamine. 3. Reaction of 5,6- and 5,7-DHT with oxygen is essential for these drugs to act as neurotoxins. Both drugs interact with the electron transfer chain of mitochondria (at the site of complex III) resulting in accelerated formation of reactive quinoidal intermediates. Metabolism of 5,7-DHT by MAO contributes to the overall in vivo neurotoxicity of this m-substituted dihydroxytryptamine.

5,7-Dihydroxytryptamine↗

Structural and biochemical changes in rat cerebral cortex after neonatal 6-hydroxydopamine administration.

Newborn rats received an intracisternal injection of 6-hydroxydopamine (100 micrograms) within 16 h after birth. Treatment effects upon noradrenaline uptake (with or without desmethylimipramine pre-incubation), endogenous noradrenaline, dopamine, and serotonin were biochemically assayed. Noradrenaline uptake and endogenous noradrenaline content were permanently reduced to less than 5% of control values. Reduction of endogenous dopamine content was less marked: at day 60, values were about 40% of controls. Serotonin content remained unaffected. Cell density countings in postnatal day 15 temporal cortex revealed an about 16% reduction in layers II and III of treated animals. These modifications of cortical geometry were discussed with reference to measurements of cortical thickness and ultrastructural observations on postnatal days 2, 5 and 15. Both supranormal involution and growth processes might result from the neurotoxin treatment. Whereas some of the degeneration processes might be due o general cytotoxic effects, this is less likely for the supranormal growth processes.

Animals↗

[Cholestatic hepatosis caused by Talinolol (Cordanum)?].

It is reported on a 38-year-old female patient who was treated for 18 days with 150 mg cordanum (talinolol) each and then fell ill with a dyspeptic clinical picture and signs of cholestase. The result of a liver biopsy was the picture of a cholestatic hepatosis. According to the results of the lymphocyte transformation test and the monocyte test as well as to the reexposition with following clinical recidivation the talinolol medication is to be regarded as cause. Pathogenetically is referred to the structural relations of talinolol to substances with paragroups as well as to a possible summation of different loads of the liver function.

Adrenergic beta-Antagonists↗

Dihydroxytryptamines as tools to study the neurobiology of serotonin.

The neurotoxins 5,6- and 5,7-dihydroxytryptamine are accepted tools for "chemical degeneration" of serotonergic (5-HT) axons in the CNS (for reviews, see [11, 12, 15, 20] ). Optimum application of these substances requires knowledge of their chemical properties, disposition in the biophase and mechanism of action. Current knowledge and concepts on this issue are described and results of recent studies utilizing 5,7-DHT uptake as a tool for localizing 5-HT neurons neuroanatomically are reviewed.

5,6-Dihydroxytryptamine↗