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[{"key": "dc.contributor.advisor", "value": "Lensu, Sanna", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Yl\u00e4nne, Jari", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Puumalainen, Veera", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2024-01-03T06:23:46Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2024-01-03T06:23:46Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2023", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/92528", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "During adulthood, new neurons are mainly generated in hippocampal dentate gyrus. This process is known as adult hippocampal neurogenesis (AHN), during which neural progenitor cells divide, and mature into adult-born dentate granule cells. Finally they integrate into hippocampal networks, which are known to take part in learning and memory. Calcium imaging methods have permitted studying the cellular level events of learning and memory in vivo. For this, genes encoding for fluorescent calcium indicators are conveyed to neuronal cells, and when coupled with micro-optical tools they enable the live monitoring of calcium activity, reflecting activation of neurons. Adeno-associated virus (AAV) is one of the most used genetic vectors for calcium indicator expression on the target cells. AAVs are regarded as safe and effective, and so recombinant AAVs are developed increasingly to deliver transgenes to target tissues. However, recent research has revealed AAVs\u2019 potency to induce cell death in many cell types, including neural progenitor cells and adult-born neurons. In this study, the AAV-induced effects on AHN were assessed by injecting saline (n=6) or AAV9 vector carrying GCaMP6s calcium indicator unilaterally to dentate gyri of adult male mice (n=10). After ca. 33 weeks, the number of adult-born neurons was determined bilaterally by doublecortin immunolabeling and confocal microscopy. In addition, the amount of GCaMP6s-derived green fluorescence (GF) was measured as a marker for transgene expression. Ipsilaterally to the injection, AAV reduced the number of adult-born neurons, i.e., neurogenesis, in comparison to saline-injected control group. The effect was local, since the number of new neurons in the contralateral hemisphere of AAV injected mice did not differ from control group. Surprisingly, no association between the GF intensity and the decrease of neurogenesis was found, and the reason for this lack of correlation remains unclear. In conclusion, this study shows the harmful effect of AAV on AHN and agrees with the scarce amount of existing data on this concern. This issue demands further research since AAVs are among the leading gene therapy vectors and research tools, also within central nervous system.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Aikuisi\u00e4ll\u00e4 uusia hermosoluja syntyy p\u00e4\u00e4osin hippokampuksen pyk\u00e4l\u00e4poimussa, jossa hermokantasolut jakautuvat ja kypsyv\u00e4t toiminnallisiksi jyv\u00e4issoluiksi, jotka liittyv\u00e4t lopulta hippokampuksen hermoverkkoihin. T\u00e4m\u00e4 ilmi\u00f6 tunnetaan aikuisi\u00e4n hippokampaalisena neurogeneesin\u00e4. Kalsiumkuvantaminen yhdistettyn\u00e4 mikro-optisiin ty\u00f6kaluihin mahdollistaa muistille ja oppimiselle t\u00e4rkeiden hippokampuksen hermosolujen aktiivisuuden tutkimisen el\u00e4v\u00e4n el\u00e4imen aivoissa. Kuvantamisen mahdollistamiseksi kohdesolu t\u00e4ytyy saada ilment\u00e4m\u00e4\u00e4n fluoresoivaa kalsiumindikaattoria. T\u00e4t\u00e4 varten soluun kuljetetaan vektorin avulla sit\u00e4 koodaava geeni. Yksi k\u00e4ytetyimmist\u00e4 vektoreista on yleisesti turvallisena pidetty adeno-assosioitu virus (AAV), ja useita siihen perustuvia tutkimusmenetelmi\u00e4 ja geeniterapiamuotoja onkin kehitetty ja yh\u00e4 kehitteill\u00e4. AAV:n on kuitenkin vastik\u00e4\u00e4n raportoitu aiheuttavan solukuolemaa useissa solutyypeiss\u00e4, mukaan lukien hermokantasolut ja aikuisi\u00e4ll\u00e4 syntyneet hermosolut. T\u00e4ss\u00e4 tutkielmassa AAV:n vaikutusta uusiin hermosoluihin tutkittiin aikuisilla uroshiirill\u00e4 (n=10), joiden toisen aivopuoliskon pyk\u00e4l\u00e4poimuihin injektoitiin GCaMP6s-kalsiumindikaattoria koodaavaa AAV9-vektoria. Noin 33 viikon kuluttua aivot siivutettiin, ja uudet hermosolut v\u00e4rj\u00e4ttiin kaksoiskortiini-vasta-aineella ja laskettiin molemmista aivopuoliskoista konfokaalimikroskoopilla. Lis\u00e4ksi GCaMP6s:n tuottaman fluoresenssin m\u00e4\u00e4r\u00e4 mitattiin hippokampuksista AAV:n ilmentymisen m\u00e4\u00e4ritt\u00e4miseksi. Uusien hermosolujen lukum\u00e4\u00e4r\u00e4\u00e4 verrattiin saman ryhm\u00e4n terveeseen aivopuoliskoon ja kontrolliryhm\u00e4\u00e4n (n=6), joille oli injektoitu AAV:n sijaan suolaliuosta. Uusien hermosolujen m\u00e4\u00e4r\u00e4 v\u00e4heni paikallisesti AAV-injektion kohdealueella hiiren hippokampuksessa. Yll\u00e4tt\u00e4en yhteytt\u00e4 fluoresenssin ja uusien hermosolujen v\u00e4henemisen v\u00e4lill\u00e4 ei l\u00f6ytynyt. T\u00e4m\u00e4 tutkielma tukee niit\u00e4 harvoja tutkimuksia, jotka ovat raportoineet AAV:n haitoista aikuisi\u00e4ll\u00e4 syntyneille hermosoluille. Koska AAV on laajalti k\u00e4yt\u00f6ss\u00e4 geeniterapian sek\u00e4 aivotutkimuksen ty\u00f6kaluna, on eritt\u00e4in t\u00e4rke\u00e4\u00e4 huomioida n\u00e4m\u00e4 tulokset ja tehd\u00e4 jatkotutkimuksia AAV:n mahdollisista haitoista eri solu- ja kudostyypeille, sek\u00e4 selvitt\u00e4\u00e4 n\u00e4kyv\u00e4tk\u00f6 vaikutukset k\u00e4yt\u00f6ksen tasolla esimerkiksi oppimisen yhteydess\u00e4.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Paivi Vuorio (paelvuor@jyu.fi) on 2024-01-03T06:23:46Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2024-01-03T06:23:46Z (GMT). No. of bitstreams: 0\n Previous issue date: 2023", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "30", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "adeno-associated virus", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "calcium imaging", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "dentate gyrus", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "neurogenesis", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Adeno-associated viral vector injection reduces adult hippocampal neurogenesis in mouse brain", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-202401031031", "language": null, "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.copyright", "value": "\u00a9 The Author(s)", "language": null, "element": "rights", "qualifier": "copyright", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "openAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": null, "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "muisti (kognitio)", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "hiiret", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "hippokampus", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "aivot", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "oppiminen", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "memory (cognition)", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "mice", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "hippocampus", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "brain", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "learning", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}]
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