f3073128e36cc8f5d6389025ddbc0149 268780.pdf f39f28ebebb2c2bddef81cae6ee4957340dfb708 268780.pdf f836bd7f23cda5e4e7409808d93fb1296b757c89de02b935a77cd1d339e98f39 268780.pdf Title: Spatial Memory Training Counteracts Hippocampal GIRK Channel Decrease in the Transgenic APPSw,Ind J9 Alzheimer’s Disease Mouse Model Subject: G-protein-gated inwardly rectifying potassium (GIRK) channels are critical determinants of neuronal excitability. They have been proposed as potential targets to restore excitatory/inhibitory balance in acute amyloidosis models, where hyperexcitability is a hallmark. However, the role of GIRK signaling in transgenic mice models of Alzheimer’s disease (AD) is largely unknown. Here, we study whether progressive amyloid- (A) accumulation in the hippocampus during aging alters GIRK channel expression in mutant -amyloid precursor protein (APPSw,Ind J9) transgenic AD mice. Additionally, we examine the impact of spatial memory training in a hippocampal-dependent task, on protein expression of GIRK subunits and Regulator of G-protein signaling 7 (RGS7) in the hippocampus of APPSw,Ind J9 mice. Firstly, we found a reduction in GIRK2 expression (the main neuronal GIRK channels subunit) in the hippocampus of 6-month-old APPSw,Ind J9 mice. Moreover, we found an aging effect on GIRK2 and GIRK3 subunits in both wild type (WT) and APPSw,Ind J9 mice. Finally, when 6-month-old animals were challenged to a spatial memory training, GIRK2 expression in the APPSw,Ind J9 mice were normalized to WT levels. Together, our results support the evidence that GIRK2 could account for the excitatory/inhibitory neurotransmission imbalance found in AD models, and training in a cognitive hippocampal dependent task may have therapeutic benefits of reversing this effect and lessen early AD deficits. Keywords: hippocampus; GIRK; Alzheimer’s disease; APPSw,Ind J9; spatial memory; excitatory/inhibitory imbalance Author: Sara Temprano-Carazo, Ana Contreras, Carlos A. Saura, Juan D. Navarro-López and Lydia Jiménez-Díaz Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Nov 3 09:51:57 2022 CET ModDate: Wed Nov 9 01:11:13 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1858491 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XWOCXD+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 ARIQJE+VnURWPalladioL Type 1 Custom yes yes no 15 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 19 0 LLLSPK+URWPalladioL-Bold Type 1 Custom yes yes no 23 0 SVHGJL+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 HIALUV+URWPalladioL-Ital Type 1 Custom yes yes no 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 50 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 53 0 WTAUCZ+CMSY10 Type 1 Builtin yes yes no 78 0 ENFMKJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 85 0 ENFMKK+PalatinoLinotype CID TrueType Identity-H yes yes yes 88 0 ENFMKL+PalatinoLinotype TrueType WinAnsi yes yes no 94 0 ENFMKN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 97 0 ENFMKJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 105 0 ENFMKK+PalatinoLinotype CID TrueType Identity-H yes yes yes 108 0 ENFMKL+PalatinoLinotype TrueType WinAnsi yes yes no 114 0 ENFMKN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 117 0 ENFMKJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 128 0 ENFMKK+PalatinoLinotype CID TrueType Identity-H yes yes yes 131 0 ENFMKL+PalatinoLinotype TrueType WinAnsi yes yes no 137 0 ENFMKN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 140 0 ENFMKJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 148 0 ENFMKK+PalatinoLinotype CID TrueType Identity-H yes yes yes 151 0 ENFMKL+PalatinoLinotype TrueType WinAnsi yes yes no 157 0 ENFMKN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 160 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-24 02:38:36 CEST RepresentationInformation: 268780.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-06-23 09:56:15 CEST Size: 1858491 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 383 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: APPSw,Ind J9 Transgenic Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Immunohistochemical Staining Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Western Blot Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Info: Title: Spatial Memory Training Counteracts Hippocampal GIRK Channel Decrease in the Transgenic APPSw,Ind J9 Alzheimer’s Disease Mouse Model Author: Sara Temprano-Carazo, Ana Contreras, Carlos A. Saura, Juan D. Navarro-López and Lydia Jiménez-Díaz Subject: G-protein-gated inwardly rectifying potassium (GIRK) channels are critical determinants of neuronal excitability. They have been proposed as potential targets to restore excitatory/inhibitory balance in acute amyloidosis models, where hyperexcitability is a hallmark. However, the role of GIRK signaling in transgenic mice models of Alzheimer’s disease (AD) is largely unknown. Here, we study whether progressive amyloid- (A) accumulation in the hippocampus during aging alters GIRK channel expression in mutant -amyloid precursor protein (APPSw,Ind J9) transgenic AD mice. Additionally, we examine the impact of spatial memory training in a hippocampal-dependent task, on protein expression of GIRK subunits and Regulator of G-protein signaling 7 (RGS7) in the hippocampus of APPSw,Ind J9 mice. Firstly, we found a reduction in GIRK2 expression (the main neuronal GIRK channels subunit) in the hippocampus of 6-month-old APPSw,Ind J9 mice. Moreover, we found an aging effect on GIRK2 and GIRK3 subunits in both wild type (WT) and APPSw,Ind J9 mice. Finally, when 6-month-old animals were challenged to a spatial memory training, GIRK2 expression in the APPSw,Ind J9 mice were normalized to WT levels. Together, our results support the evidence that GIRK2 could account for the excitatory/inhibitory neurotransmission imbalance found in AD models, and training in a cognitive hippocampal dependent task may have therapeutic benefits of reversing this effect and lessen early AD deficits. 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