title: Neuroglial expression of the MHCI pathway and PirB receptor is upregulated in the hippocampus with advanced aging.
abstract: The hippocampus undergoes changes with aging that impact neuronal function, such as synapse loss and altered neurotransmitter release. Nearly half of the aged population also develops deficits in spatial learning and memory. To identify age-related hippocampal changes that may contribute to cognitive decline, transcriptomic analysis of synaptosome preparations from adult (12 months) and aged (28 months) Fischer 344-Brown Norway rats assessed for spatial learning and memory was performed. Bioinformatic analysis identified the MHCI pathway as significantly upregulated with aging. Age-related increases in mRNAs encoding the MHCI genes RT1-A1, RT1-A2, and RT1-A3 were confirmed by qPCR in synaptosomes and in CA1 and CA3 dissections. Elevated levels of the MHCI cofactor (B2m), antigen-loading components (Tap1, Tap2, Tapbp), and two known MHCI receptors (PirB, Klra2) were also confirmed. Protein expression of MHCI was elevated with aging in synaptosomes, CA1, and DG, while PirB protein expression was induced in both CA1 and DG. MHCI expression was localized to microglia and neuronal excitatory postsynaptic densities, and PirB was localized to neuronal somata, axons, and dendrites. Induction of the MHCI antigen processing and presentation pathway in hippocampal neurons and glia may contribute to age-related hippocampal dysfunction by increasing neuroimmune signaling or altering synaptic homeostasis.
authors.affiliation: Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: VanGuilder Starkey
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Van Kirk
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Bixler
authors.forename: Caesar G
authors.initials: CG
authors.lastname: Imperio
authors.forename: Vijay P
authors.initials: VP
authors.lastname: Kale
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Serfass
authors.forename: Julie A
authors.initials: JA
authors.lastname: Farley
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.forename: Junie P
authors.initials: JP
authors.lastname: Warrington
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Matthew
authors.initials: M
authors.lastname: Mitschelen
authors.forename: William E
authors.initials: WE
authors.lastname: Sonntag
authors.forename: Willard M
authors.initials: WM
authors.lastname: Freeman
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D002678:Chimera; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011971:Receptors, Immunologic / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D059467:Transcriptome / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; C491380:Pirb protein, rat; D011971:Receptors, Immunologic; C038353:histocompatibility antigens RT, rat