The University of Southampton
University of Southampton Institutional Repository

Heparin injection into the adult rat hippocampus induces seizures in the absence of macroscopic abnormalities

Heparin injection into the adult rat hippocampus induces seizures in the absence of macroscopic abnormalities
Heparin injection into the adult rat hippocampus induces seizures in the absence of macroscopic abnormalities
The pathological hallmarks of Alzheimer's disease include neurofibrillary tangles, neuropil threads and neuritic plaques. Neurofibrillary tangles and neuropil 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 that sulphated 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 threads8,16,18 while dermatan sulphate, chondroitin sulphate and keratan sulphate immunoreactivity is found around neuritic plaques17 in brains of Alzheimer's disease patients. Furthermore,in vitro studies demonstrate that sulphated glycosaminoglycaus 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 properties associated with tau isolated from Alzheimer's disease brain.8,12 Thus, we were interested to learn whether intracerebral injection of the sulphated glycosaminoglycan 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 unexpected effect further in vivo and by using in vitro electrophysiological techniques.
alzheimer's, disease, electrophysiology, epilepsy, extracellular matrix, glycosaminoglycans, subiculum
0306-4522
329-333
Mudher, A.K.
ce0ccb35-ac49-4b6c-92b4-8dd5e78ac119
Mellanby, J.
17c8da1d-5ad3-4b71-868e-f4416a4abc39
McMath, H.
253d056a-d9b6-46b1-9074-fc6a4a0bebf0
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Greene, J.R.T.
b7eea969-7be7-49f0-8788-5df4f5bab21e
Mudher, A.K.
ce0ccb35-ac49-4b6c-92b4-8dd5e78ac119
Mellanby, J.
17c8da1d-5ad3-4b71-868e-f4416a4abc39
McMath, H.
253d056a-d9b6-46b1-9074-fc6a4a0bebf0
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Greene, J.R.T.
b7eea969-7be7-49f0-8788-5df4f5bab21e

Mudher, A.K., Mellanby, J., McMath, H., Perry, V.H. and Greene, J.R.T. (1999) Heparin injection into the adult rat hippocampus induces seizures in the absence of macroscopic abnormalities. Neuroscience, 89 (2), 329-333. (doi:10.1016/S0306-4522(98)00533-8).

Record type: Article

Abstract

The pathological hallmarks of Alzheimer's disease include neurofibrillary tangles, neuropil threads and neuritic plaques. Neurofibrillary tangles and neuropil 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 that sulphated 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 threads8,16,18 while dermatan sulphate, chondroitin sulphate and keratan sulphate immunoreactivity is found around neuritic plaques17 in brains of Alzheimer's disease patients. Furthermore,in vitro studies demonstrate that sulphated glycosaminoglycaus 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 properties associated with tau isolated from Alzheimer's disease brain.8,12 Thus, we were interested to learn whether intracerebral injection of the sulphated glycosaminoglycan 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 unexpected effect further in vivo and by using in vitro electrophysiological techniques.

This record has no associated files available for download.

More information

Published date: 1 March 1999
Keywords: alzheimer's, disease, electrophysiology, epilepsy, extracellular matrix, glycosaminoglycans, subiculum

Identifiers

Local EPrints ID: 56693
URI: http://eprints.soton.ac.uk/id/eprint/56693
ISSN: 0306-4522
PURE UUID: eef3d0dd-50e0-4028-85a0-d6ffda76c257

Catalogue record

Date deposited: 22 Aug 2008
Last modified: 15 Mar 2024 11:03

Export record

Altmetrics

Contributors

Author: A.K. Mudher
Author: J. Mellanby
Author: H. McMath
Author: V.H. Perry
Author: J.R.T. Greene

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×