title: Cerebral level of vGlut1 is increased and level of glycine is decreased in TgSwDI mice.
abstract: Amyloid-β (Aβ) deposition, one of the main hallmarks of Alzheimer's disease (AD), has been linked to glutamatergic dysfunction, i.e., increased stimulation of synaptic glutamate receptors that may ultimately result in neuronal loss. It was our aim to study the effect of Aβ on multiple components of the glutamatergic system, and therefore we assessed the expression of several glutamate-related proteins and amino acids in the TgSwDI mouse model for Aβ pathology. We determined that in TgSwDI mice, levels of several amino acids are altered, in particular that of glycine. Protein changes were only found in 9-month-old TgSwDI mice with extensive Aβ deposits, with the most prominent change an increased expression of vesicular glutamate transporter 1 (vGlut1). Autoradiography experiments demonstrated that, while the number of activated N-methyl-D-aspartic acid (NMDA) receptors was unchanged in TgSwDI mice, binding of the NMDA receptor radioligand [3H]MDL-105,519 to the glycine-binding site of these receptors was increased. Although there are some discrepancies between our results and those found in AD patients, our results suggest that several components of the glutamatergic system might serve as meaningful markers to monitor the progression of AD.
authors.affiliation: Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Nienke M
authors.initials: NM
authors.lastname: Timmer
authors.affiliation: Department of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Metaxas
authors.affiliation: Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: van der Stelt
authors.affiliation: Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Leo A J
authors.initials: LA
authors.lastname: Kluijtmans
authors.affiliation: Department of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Bart N
authors.initials: BN
authors.lastname: van Berckel
authors.affiliation: Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud university medical center, Nijmegen, The Netherlands Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018698:Glutamic Acid; D005998:Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D050598:Vesicular Glutamate Transport Protein 1
keywords: Alzheimer's disease; TgSwDI mice; amino acid analysis; amyloid-β; autoradiography; glutamate; glycine; vesicular glutamate transporter 1; western blot