title: Glutamate presynaptic vesicular transporter and postsynaptic receptor levels correlate with spatial memory status in aging rat models.
abstract: In humans, memory capacities are generally affected with aging, even without any reported neurologic disorders. The mechanisms behind cognitive decline are not well understood. We studied here whether postsynaptic glutamate receptor and presynaptic vesicular glutamate transporters (VGLUTs) levels may change in the course of aging and be related to cognitive abilities using various age-impaired (AI) or age-unimpaired rat strains. Twenty-four-month-old Long-Evans (LE) rats with intact spatial memory maintained postsynaptic ionotropic glutamate receptor levels in the hippocampal-adjacent cortex similar to those of young animals. In contrast, AI rats showed significantly reduced expression of ionotropic glutamate receptor GluR2, NR2A and NR2B subunits. In AI LE rats, VGLUT1 and VGLUT2 levels were increased and negatively correlated with receptor levels as shown by principal component analysis and correlation matrices. We also investigated whether glutamatergic receptors and VGLUT levels were altered in the obesity-resistant LOU/C/Jall (LOU) rat strain which is characterized by intact memory despite aging. No difference was observed between 24-month-old LOU rats and their young counterparts. Taken together, the unaltered spatial memory performance of 24-month-old age-unimpaired LE and LOU rats suggests that intact coordination of the presynaptic and postsynaptic hippocampal-adjacent cortex glutamatergic networks may be important for successful cognitive aging. Accordingly, altered expression of presynaptic and postsynaptic glutamatergic components, such as in AI LE rats, could be considered a marker of age-related cognitive deficits.
authors.affiliation: Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Laboratory of Neuroendocrinology of Aging, Centre Hospitalier de l'Université de Montréal Research Center, Montreal, Quebec, Canada; Department of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ménard
authors.affiliation: Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
authors.forename: Rémi
authors.initials: R
authors.lastname: Quirion
authors.affiliation: Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Erika
authors.initials: E
authors.lastname: Vigneault
authors.affiliation: Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bouchard
authors.affiliation: Institut Universitaire de Gériatrie de Montréal Research Center, University of Montreal, Montreal, Quebec, Canada; Department of Nutrition, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Guylaine
authors.initials: G
authors.lastname: Ferland
authors.affiliation: Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada; INSERM U952, CNRS UMR7224, Université Pierre et Marie Curie, Paris, France.
authors.forename: Salah
authors.initials: S
authors.lastname: El Mestikawy
authors.affiliation: Laboratory of Neuroendocrinology of Aging, Centre Hospitalier de l'Université de Montréal Research Center, Montreal, Quebec, Canada; Department of Medicine, University of Montreal, Montreal, Quebec, Canada. Electronic address: pierrette.gaudreau@umontreal.ca.
authors.forename: Pierrette
authors.initials: P
authors.lastname: Gaudreau
mesh_terms: D000375:Aging / Q000523:psychology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003072:Cognition Disorders / Q000175:diagnosis; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D011919:Rats, Inbred Strains; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism*; D065852:Spatial Memory / Q000502:physiology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics* / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C493475:Slc17a6 protein, rat; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPA; Aging; Glutamate receptors; NMDA; Spatial memory; VGLUT; mGluR