title: Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain.
abstract: Major histocompatibility complex class I (MHCI) proteins have been implicated in neuronal function through the modulation of neuritogenesis, synaptogenesis, synaptic plasticity, and memory consolidation during development. However, the involvement of MHCI in the aged brain is unclear. Here we demonstrate that MHCI deficiency results in significant dendritic atrophy along with an increase in thin dendritic spines and a reduction in stubby spines in the hippocampus of aged (12 month old) mice. Ultrastructural analyses revealed a decrease in spine head diameter and post synaptic density (PSD) area, as well as an increase in overall synapse density, and non-perforated, small spines. Interestingly, we found that the changes in synapse density and morphology appear relatively late (after the age of 6 months). Finally, we found a significant age dependent increase in the levels of the glutamate receptor, GluN2B in aged MHCI knockout mice, with no change in GluA2/3, VGluT1, PSD95 or synaptophysin. These results indicate that MHCI may be also be involved in maintaining brain integrity at post-developmental stages notably in the modulation of neuronal and spine morphology and synaptic function during non-pathological aging which could have significant implications for cognitive function.
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Department of Mental Health and Psychiatry, Division of General Psychiatry, University Hospitals of Geneva, Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Maciej J
authors.initials: MJ
authors.lastname: Lazarczyk
authors.affiliation: University of Konstanz, Doerenkamp-Zbinden, Universitätsstrasse. 10, 78457 Konstanz, Germany.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Kemmler
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, British Columbia, V6T 1Z4, Canada.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Eyford
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Short
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Merina
authors.initials: M
authors.lastname: Varghese
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Sowa
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Dickstein
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Yuk
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, British Columbia, V6T 1Z4, Canada.|Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Kaan E
authors.initials: KE
authors.lastname: Biron
authors.affiliation: University of Konstanz, Doerenkamp-Zbinden, Universitätsstrasse. 10, 78457 Konstanz, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, British Columbia, V6T 1Z4, Canada.|Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.|Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.|Department of Zoology, University of British Columbia, 2370-6270 University Blvd., Vancouver, BC, V6T 1Z4, Canada.|Department of Medical Genetics, 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: Jefferies
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Dara L
authors.initials: DL
authors.lastname: Dickstein
mesh_terms: D000375:Aging; D000818:Animals; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000502:physiology*
chemical_list: D015395:Histocompatibility Antigens Class I