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

Sensors

Sean D. O'Shea¹  Imelda M. Smith²  Olive M. McCabe¹  Michelle M. Cronin¹  Dominic M. Walsh² 

[1] Applied Neurotherapeutics Research Group, Conway Institute, University College Dublin, Dublin 4, Ireland;Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Dublin 4, Ireland; E-mail:

关键词: Alzheimer's Disease;    Amyloid β-protein;    Microdialysis;    Glutamate;    GABA;    Release;   

DOI  :  10.3390/s8117428

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2008 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.