{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T18:07:33Z","timestamp":1780423653040,"version":"3.54.1"},"reference-count":86,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2024,7,30]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Alzheimer\u2019s disease (AD) is the most common neurodegenerative disease. Unfortunately, efficient and affordable treatments are still lacking for this neurodegenerative disorder, it is therefore urgent to identify new pharmacological targets. Astrocytes are playing a crucial role in the tuning of synaptic transmission and several studies have pointed out severe astrocyte reactivity in AD. Reactive astrocytes show altered physiology and function, suggesting they could have a role in the early pathophysiology of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      We aimed to characterize early synaptic impairments in the\n                      <jats:italic toggle=\"yes\">App<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">NL<\/jats:italic>\n                        -\n                        <jats:italic toggle=\"yes\">F<\/jats:italic>\n                      <\/jats:sup>\n                      knock-in mouse model of AD, especially to understand the contribution of astrocytes to early brain dysfunctions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic toggle=\"yes\">App<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">NL<\/jats:italic>\n                        -\n                        <jats:italic toggle=\"yes\">F<\/jats:italic>\n                      <\/jats:sup>\n                      mouse model carries two disease-causing mutations inserted in the amyloid precursor protein gene. This strain does not start to develop amyloid-\u03b2 plaques until 9 months of age. Thanks to electrophysiology, we investigated synaptic function, at both neuronal and astrocytic levels, in 6-month-old animals and correlate the synaptic activity with emotional behavior.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Electrophysiological recordings in the hippocampus revealed an overall synaptic mistuning at a pre-plaque stage of the pathology, associated to an intact social memory but a stronger depressive-like behavior. Astrocytes displayed a reactive-like morphology and a higher tonic GABA current compared to control mice. Interestingly, we here show that the synaptic impairments in hippocampal slices are partially corrected by a pre-treatment with the monoamine oxidase B blocker deprenyl or the fast-acting antidepressant ketamine (5\u200amg\/kg).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We propose that reactive astrocytes can induce synaptic mistuning early in AD, before plaques deposition, and that these changes are associated with emotional symptoms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-231461","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T10:48:27Z","timestamp":1720781307000},"page":"1017-1037","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Early Astrocytic Dysfunction Is Associated with Mistuned Synapses as well as Anxiety and Depressive-Like Behavior in the\n                    <i>App<\/i>\n                    <sup>\n                      <i>NL<\/i>\n                      -\n                      <i>F<\/i>\n                    <\/sup>\n                    Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"100","author":[{"given":"Benjamin","family":"Portal","sequence":"first","affiliation":[{"name":"Uppsala University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moa","family":"S\u00f6dergren","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teo","family":"Par\u00e9s i Borrell","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Giraud","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole G.","family":"Metzendorf","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Hultqvist","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Karolinska Institutet","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Lindskog","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Sweden"]},{"name":"Karolinska Institutet","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"key":"e_1_3_6_2_2","unstructured":"FerriCP SousaR AlbaneseE RibeiroWS MHonyashikiM AcostaD BlomM DudgeonS FrantzN GeigerA JensenA KetteringhamA KinnairdL MartenssonB ReesG SchaperF SplaineM TamiT WesterlindK WortmannM (2009) World Alzheimer\u2019s Report 2009. Alzheimer\u2019s Disease International London."},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2013.15.4\/hjahn"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201442"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.5.857"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.04.022"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113613"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07478.x"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15875"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2410"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-0839-1"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512513"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112787"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2023.103457"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000260698.46517.8f"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz320"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0080-x"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01257-0"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2020.11.007"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83008-3"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1969.00480130123013"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.03.001"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-014-2859-7"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12111469"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.3671"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-150"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-022-00641-1"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00783-4"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.440080208"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2014.00141"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170045"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201797397"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3697"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/cn500105p"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.009487"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.878303"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122552"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02289-4"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhz016"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.01.019"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184334"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071705"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0582-9"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01617-0"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.278754"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210629"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.09.044"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.036"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.103895"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64012-3.00002-2"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.02.017"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2022.12.006"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115991"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.01.008"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00457-0"},{"key":"e_1_3_6_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2303"},{"key":"e_1_3_6_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.11.028"},{"key":"e_1_3_6_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3639"},{"key":"e_1_3_6_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.006"},{"key":"e_1_3_6_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-023-00822-1"},{"key":"e_1_3_6_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(06)60005-8"},{"key":"e_1_3_6_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1377"},{"key":"e_1_3_6_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2018.08.015"},{"key":"e_1_3_6_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyy037"},{"key":"e_1_3_6_67_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113227"},{"key":"e_1_3_6_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2013.06.002"},{"key":"e_1_3_6_69_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000567"},{"key":"e_1_3_6_70_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-200093"},{"key":"e_1_3_6_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(99)00230-9"},{"key":"e_1_3_6_72_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00186"},{"key":"e_1_3_6_73_2","doi-asserted-by":"publisher","DOI":"10.3390\/neurolint14020025"},{"key":"e_1_3_6_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.05.010"},{"key":"e_1_3_6_75_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-021-01180-6"},{"key":"e_1_3_6_76_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-020-00627-z"},{"key":"e_1_3_6_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2023.03.012"},{"key":"e_1_3_6_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.02.014"},{"key":"e_1_3_6_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01270-2"},{"key":"e_1_3_6_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2801"},{"key":"e_1_3_6_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2008.11.020"},{"key":"e_1_3_6_82_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-215304"},{"key":"e_1_3_6_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108158"},{"key":"e_1_3_6_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2022.109383"},{"key":"e_1_3_6_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.03.068"},{"key":"e_1_3_6_86_2","doi-asserted-by":"publisher","DOI":"10.5582\/ddt.2021.01061"},{"key":"e_1_3_6_87_2","first-page":"1479","article-title":"Cholinesterase inhibitors as Alzheimer\u2019s therapeutics (Review)","volume":"20","author":"Sharma K","year":"2019","unstructured":"SharmaK (2019) Cholinesterase inhibitors as Alzheimer\u2019s therapeutics (Review). Mol Med Rep 20, 1479\u20131487.","journal-title":"Mol Med Rep"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-231461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-231461","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-231461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T17:48:45Z","timestamp":1780422525000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-231461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,4]]},"references-count":86,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,7,30]]}},"alternative-id":["10.3233\/JAD-231461"],"URL":"https:\/\/doi.org\/10.3233\/jad-231461","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.05.12.540486","asserted-by":"object"}]},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,4]]}}}