Association of Parkinson's disease with symptoms of attention deficit hyperactivity disorder in childhood.

被引量：9 发表：2007

Kynurenines, Parkinson's disease and other neurodegenerative disorders: preclinical and clinical studies.

被引量：41 发表：2006

Neuronal degeneration and reorganization: a mutual principle in pathological and in healthy interactions of limbic and prefrontal circuits.

:Based on developmental principles and insights from animal research about neuroplasticity in cell assemblies, this article is to propose a view of plasticity that promotes a link between hippocampal and prefrontal structure and function. Both the mitotic activity (counting of BrdU-labeled cells) in hippocampal dentatus and the maturation of dopamine fibres (quantitative immunochemistry of mesoprefrontal projection) in the prefrontal cortex proved to be a measurable combination for investigating the complex chain of events that relate activity dependent neuroplasticity to normal as well as to pathological maturational processes. With our animal model we demonstrate that both rearing conditions and neuroactive substances can effectively interfere with developmental plasticity and induce a malfunctional adaptation of prefrontal structures and neurotransmitter systems (dopamine, GABA). In the hippocampal dentatus, where ontogenetic plasticity proved to be preserved by continued neuro- and synaptogenesis, serious damage can be internalized without simultaneous disruption of neural dynamics offering an approach to reverse dysfunctional reorganization in the prefrontal cortex.

被引量：8 发表：2000

Neurorescuing effects of the GAPDH ligand CGP 3466B.

:(-)-Deprenyl, used for the treatment of Parkinson's disease, was reported to possess neurorescuing/antiapoptotic effects independent of its MAO-B inhibiting properties. It is metabolized to (-)-desmethyldeprenyl, which seems to be the active principle, and further to (-)-amphetamine and (-)-methamphetamine, which antagonize its rescuing effects. These complications may explain the limited neurorescuing potential of (-)-deprenyl observed clinically. CGP 3466 (dibenzo[b,f]oxepin-10-ylmethyl-methyl-prop-2-ynyl-amine), structurally related to (-)-deprenyl, exhibits virtually no MAO-B nor MAO-A inhibiting properties and is not metabolized to amphetamines. It was shown to bind to glyceraldehyde-3-phosphate dehydrogenase, a glycolytic enzyme with multiple other functions including an involvement in apoptosis, and shows neurorescuing properties qualitatively similar to, but about 100-fold more potent than those of (-)-deprenyl in several in vitro and in vivo paradigms. In concentrations ranging from 10(-13)-10(-5) M, it rescues partially differentiated PC12 cells from apoptosis induced by trophic withdrawal, cerebellar granule cells from apoptosis induced by cytosine arabinoside, rat embryonic mesencephalic dopaminergic cells from death caused by MPP+, and PAJU human neuroblastoma cells from death caused by rotenone. However, it did not affect apoptosis elicited by a variety of agents in rapidly proliferating cells from thymus or skin or in liver or kidney cells. In vivo, it rescued facial motor neuron cell bodies in rat pups after axotomy, rat hippocampal CA1 neurons after transient ischemia/hypoxia, and mouse nigral dopaminergic cell bodies from death induced by MPTP, in doses ranging between 0.0003 and 0.1 mg/kg p.o. or s.c., depending on the model. It also partially prevented the loss of tyrosine hydroxylase immunoreactivity in the substantia nigra of 6-OHDA-lesioned rats and improved motor function in these animals. Moreover, it prolonged the life-span of progressive motor neuronopathy (pmn) mice (a model for ALS), preserved their body weight and improved their motor performance. This was accompanied by a decreased loss of motor neurons and motor neuron fibers, and protection of mitochondria. The active concentration- or dose-ranges in the different in vitro and in vivo paradigms were remarkably similar. In several paradigms, bell-shaped dose-response curves were observed, the rescuing effect being lost above about 1 mg/kg, a fact that must be considered in clinical investigations.

被引量：14 发表：2000

Ageing and Dementia 1999. Proceedings of an international symposium. September 24-26, 1999, Graz, Austria.

被引量：- 发表：2000