Neurotoxine und Neuroprotektion: Bedeutung radikalischer Mechanismen und der Atmungsketteninhibition fuer die Aetiologie des Parkinsonsyndroms, der Neurodegeneration und des Alterungsprozesses Schlussbericht

There are no animal models for the investigation of the causes and progression of neurodegenerative diseases - such as Parkinson's Disease -suitable for searching out the pathological mechanisms which may elicit and maintain a progressive disease process. Up till now only a few of the factors that might contribute to the multiactorial pathogenesis of Parkinson's Disease have been established. A large-scale depolyment of non-human primates could not be considered. Rats, subjected to oxidative stress, exhibit a gradually developing assortment of pathological symptoms which strikingly involve the mediation of the dopaminergic system. The pathological symptoms are susceptible to therapeutic interventions. The animals undergo various stages of a set of pathological symptoms which manifests itself among others in a reluctance to undertake changes of rapid motor strategies. They exhibit a diminished ability to learn and to pay attention. Brain regions where such lesions may be elicited are highly specific. At an advanced age, the consequency of oxidative stress show a loss of the D1 mRNA in the dorsal statum without concomitant cell loss. (orig.)Available from TIB Hannover: F99B1195 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Monocarboxylate transporters in the central nervous system: distribution, regulation and function.

Monocarboxylate transporters (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, pyruvate, as well as ketone bodies. They belong to a larger family of transporters composed of 14 members in mammals based on sequence homologies. MCTs are found in various tissues including the brain where three isoforms, MCT1, MCT2 and MCT4, have been described. Each of these isoforms exhibits a distinct regional and cellular distribution in rodent brain. At the cellular level, MCT1 is expressed by endothelial cells of microvessels, by ependymocytes as well as by astrocytes. MCT4 expression appears to be specific for astrocytes. By contrast, the predominant neuronal monocarboxylate transporter is MCT2. Interestingly, part of MCT2 immunoreactivity is located at postsynaptic sites, suggesting a particular role of monocarboxylates and their transporters in synaptic transmission. In addition to variation in expression during development and upon nutritional modifications, new data indicate that MCT expression is regulated at the translational level by neurotransmitters. Understanding how transport of monocarboxylates is regulated could be of particular importance not only for neuroenergetics but also for areas such as functional brain imaging, regulation of food intake and glucose homeostasis, or for central nervous system disorders such as ischaemia and neurodegenerative diseases