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Titolo:
Heparin injection into the adult rat hippocampus induces seizures in the absence of macroscopic abnormalities
Autore:
Mudher, AK; Mellanby, J; McMath, H; Perry, VH; Greene, JRT;
Indirizzi:
Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England Univ Oxford Oxford England OX1 3QT pt Pharmacol, Oxford OX1 3QT, England Dept Expt Psychol, Oxford OX1 3PS, England Dept Expt Psychol Oxford England OX1 3PS sychol, Oxford OX1 3PS, England
Titolo Testata:
NEUROSCIENCE
fascicolo: 2, volume: 89, anno: 1999,
pagine: 329 - 333
SICI:
0306-4522(199903)89:2<329:HIITAR>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
PAIRED HELICAL FILAMENTS; ALZHEIMERS-DISEASE; PROTEIN-TAU; PROTEOGLYCAN; SULFATE; NEURONS; BRAIN;
Keywords:
Alzheimer's disease; electrophysiology; epilepsy; extracellular matrix; glycosaminoglycans; subiculum;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
19
Recensione:
Indirizzi per estratti:
Indirizzo: Mudher, AK Inst Psychiat, De Crespigny Pk, Denmark Hill, London SE5 8AF, England Inst Psychiat De Crespigny Pk, Denmark Hill London England SE5 8AF
Citazione:
A.K. Mudher et al., "Heparin injection into the adult rat hippocampus induces seizures in the absence of macroscopic abnormalities", NEUROSCIENC, 89(2), 1999, pp. 329-333

Abstract

The pathological hallmarks of Alzheimer's disease include neurofibrillary tangles, neuropil threads and neuritic plaques. Neurofibrillary tangles andneuropil threads are comprised of paired helical filaments which are themselves composed of a hyperphosphorylated form of the microtubule-associated protein tau.(10,13) Neuritic plaques are extracellular deposits of aggregated beta amyloid associated with neurites containing hyperphosphorylated tau. (3) The mechanisms by which the neurofibrillary tangles and neuritic plaques develop in Alzhemier's disease are not clear but it is hypothesized thatsulphated glycosaminoglycans are important in their formation. This impression is based on the finding that the glycosaminoglycan, heparan sulphate, is found associated with neurofibrillary tangles, neuritic plaques and neuropil threads(8,16,18) while dermatan sulphate, chondroitin sulphate and keratan sulphate immunoreactivity is found around neuritic plaques(17) in brains of Alzheimer's disease patients. Furthermore, in vitro studies demonstrate that sulphated glycosaminoglycans such as heparan sulphate and the closely related molecule heparin interact with tau and potentiate its phosphorylation by a number of serine/threonine kinases, reduce its ability to bind to microtubules and induce paired helical filament formation, all propertiesassociated with tau isolated from Alzheimer's disease brain.(8,12) Thus, we were interested to learn whether intracerebral injection of the sulphatedglycosaminoglycan heparin would give rise to alterations in the cytoskeletal protein tau in the rat brain. Although no cytoskeletal changes were observed, to our considerable surprise we found that the intrahippocampal injection of heparin gave rise to seizures. We have investigated this unexpectedeffect further in vivo and by using in vitro electrophysiological techniques. (C) 1998 IBRO. Published by Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 19:17:54