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Sensors 2008, 8(11), 7428-7437; doi:10.3390/s8117428
Article

Intracerebroventricular Administration of Amyloid β-protein Oligomers Selectively Increases Dorsal Hippocampal Dialysate Glutamate Levels in the Awake Rat

1, 2, 1, 1, 2
 and 1,3,4,*
1 Applied Neurotherapeutics Research Group, Conway Institute, University College Dublin, Dublin 4, Ireland 2 Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Dublin 4, Ireland 3 Graduate Medical School, University of Limerick, Limerick, Ireland 4 Materials and Surface Science Institute, University of Limerick, Limerick, Ireland
* Author to whom correspondence should be addressed.
Received: 9 July 2008 / Revised: 10 November 2008 / Accepted: 11 November 2008 / Published: 19 November 2008
(This article belongs to the Special Issue Amperometric Sensors and Techniques for Neurochemical Monitoring)
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Abstract

Extensive evidence supports an important role for soluble oligomers of the amyloid β-protein (Aβ) in Alzheimer’s Disease pathogenesis. In the present study we combined intracerebroventricular (icv) injections with brain microdialysis technology in the fully conscious rat to assess the effects of icv administered SDS-stable low-n Aβ oligomers (principally dimers and trimers) on excitatory and inhibitory amino acid transmission in the ipsilateral dorsal hippocampus. Microdialysis was employed to assess the effect of icv administration of Aβ monomers and Aβ oligomers on dialysate glutamate, aspartate and GABA levels in the dorsal hippocampus. Administration of Aβ oligomers was associated with a +183% increase (p<0.0001 vs. Aβ monomer-injected control) in dorsal hippocampal glutamate levels which was still increasing at the end of the experiment (260 min), whereas aspartate and GABA levels were unaffected throughout. These findings demonstrate that icv administration and microdialysis technology can be successfully combined in the awake rat and suggests that altered dorsal hippocampal glutamate transmission may be a useful target for pharmacological intervention in Alzheimer’s Disease.
Keywords: Alzheimer’s Disease; Amyloid β-protein; Microdialysis; Glutamate; GABA; Release Alzheimer’s Disease; Amyloid β-protein; Microdialysis; Glutamate; GABA; Release
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

O’Shea, S.D.; Smith, I.M.; McCabe, O.M.; Cronin, M.M.; Walsh, D.M.; O’Connor, W.T. Intracerebroventricular Administration of Amyloid β-protein Oligomers Selectively Increases Dorsal Hippocampal Dialysate Glutamate Levels in the Awake Rat. Sensors 2008, 8, 7428-7437.

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