Impaired astrocytic Ca 2+ signaling in awake-behaving Alzheimer's disease transgenic mice
Increased astrocytic Ca signaling has been shown in Alzheimer's disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca signals in the neocortex of awake-behaving...
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| Veröffentlicht in: | eLife 2022-07, Vol.11 |
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| creator | Åbjørsbråten, Knut Sindre Skaaraas, Gry H E Syverstad Cunen, Céline Bjørnstad, Daniel M Binder, Kristin M Gullestad Bojarskaite, Laura Jensen, Vidar Nilsson, Lars N G Rao, Shreyas B Tang, Wannan Hermansen, Gudmund Horn Nagelhus, Erlend A Ottersen, Ole Petter Torp, Reidun Enger, Rune |
| description | Increased astrocytic Ca
signaling has been shown in Alzheimer's disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca
signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca
signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca
response to locomotion and an uncoupling of pupil responses and astrocytic Ca
signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRAB
, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca
responses. Our data points to a dysfunction in the norepinephrine-astrocyte Ca
activity axis, which may account for some of the cognitive deficits observed in Alzheimer's disease. |
| doi_str_mv | 10.7554/eLife.75055 |
| format | Article |
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signaling has been shown in Alzheimer's disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca
signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca
signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca
response to locomotion and an uncoupling of pupil responses and astrocytic Ca
signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRAB
, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca
responses. Our data points to a dysfunction in the norepinephrine-astrocyte Ca
activity axis, which may account for some of the cognitive deficits observed in Alzheimer's disease.</description><identifier>EISSN: 2050-084X</identifier><identifier>DOI: 10.7554/eLife.75055</identifier><identifier>PMID: 35833623</identifier><language>eng</language><publisher>England</publisher><subject>Alzheimer Disease - genetics ; Animals ; Astrocytes - physiology ; Calcium Signaling - physiology ; Mice ; Mice, Transgenic ; Norepinephrine ; Wakefulness - physiology</subject><ispartof>eLife, 2022-07, Vol.11</ispartof><rights>2022, Åbjørsbråten, Skaaraas et al.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0001-9418-7117</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35833623$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Åbjørsbråten, Knut Sindre</creatorcontrib><creatorcontrib>Skaaraas, Gry H E Syverstad</creatorcontrib><creatorcontrib>Cunen, Céline</creatorcontrib><creatorcontrib>Bjørnstad, Daniel M</creatorcontrib><creatorcontrib>Binder, Kristin M Gullestad</creatorcontrib><creatorcontrib>Bojarskaite, Laura</creatorcontrib><creatorcontrib>Jensen, Vidar</creatorcontrib><creatorcontrib>Nilsson, Lars N G</creatorcontrib><creatorcontrib>Rao, Shreyas B</creatorcontrib><creatorcontrib>Tang, Wannan</creatorcontrib><creatorcontrib>Hermansen, Gudmund Horn</creatorcontrib><creatorcontrib>Nagelhus, Erlend A</creatorcontrib><creatorcontrib>Ottersen, Ole Petter</creatorcontrib><creatorcontrib>Torp, Reidun</creatorcontrib><creatorcontrib>Enger, Rune</creatorcontrib><title>Impaired astrocytic Ca 2+ signaling in awake-behaving Alzheimer's disease transgenic mice</title><title>eLife</title><addtitle>Elife</addtitle><description>Increased astrocytic Ca
signaling has been shown in Alzheimer's disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca
signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca
signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca
response to locomotion and an uncoupling of pupil responses and astrocytic Ca
signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRAB
, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca
responses. Our data points to a dysfunction in the norepinephrine-astrocyte Ca
activity axis, which may account for some of the cognitive deficits observed in Alzheimer's disease.</description><subject>Alzheimer Disease - genetics</subject><subject>Animals</subject><subject>Astrocytes - physiology</subject><subject>Calcium Signaling - physiology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Norepinephrine</subject><subject>Wakefulness - physiology</subject><issn>2050-084X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFjjGLwkAUhBfhUNFU9rKdhUTXbFZzpYiiYGmhlTyTZ3ya3Qv7cif66y8HWt80M3wMwwjRm6jRzJh4jFs6Yx2VMQ3RjpRRoUrifUsEzFdVaxYnyeSzKVraJFpPI90Wh40tgTxmErjyX-mjolQuQEZDyZQ7KMjlkpyEO9wwPOEFfv7IvHhekCz6AcuMGIFRVh4c5-jqAUspdsXHGQrG4OUd0V8td4t1WH6fLGbH0pMF_zi-v-h_C7-coESx</recordid><startdate>20220714</startdate><enddate>20220714</enddate><creator>Åbjørsbråten, Knut Sindre</creator><creator>Skaaraas, Gry H E Syverstad</creator><creator>Cunen, Céline</creator><creator>Bjørnstad, Daniel M</creator><creator>Binder, Kristin M Gullestad</creator><creator>Bojarskaite, Laura</creator><creator>Jensen, Vidar</creator><creator>Nilsson, Lars N G</creator><creator>Rao, Shreyas B</creator><creator>Tang, Wannan</creator><creator>Hermansen, Gudmund Horn</creator><creator>Nagelhus, Erlend A</creator><creator>Ottersen, Ole Petter</creator><creator>Torp, Reidun</creator><creator>Enger, Rune</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><orcidid>https://orcid.org/0000-0001-9418-7117</orcidid></search><sort><creationdate>20220714</creationdate><title>Impaired astrocytic Ca 2+ signaling in awake-behaving Alzheimer's disease transgenic mice</title><author>Åbjørsbråten, Knut Sindre ; Skaaraas, Gry H E Syverstad ; Cunen, Céline ; Bjørnstad, Daniel M ; Binder, Kristin M Gullestad ; Bojarskaite, Laura ; Jensen, Vidar ; Nilsson, Lars N G ; Rao, Shreyas B ; Tang, Wannan ; Hermansen, Gudmund Horn ; Nagelhus, Erlend A ; Ottersen, Ole Petter ; Torp, Reidun ; Enger, Rune</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_358336233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alzheimer Disease - genetics</topic><topic>Animals</topic><topic>Astrocytes - physiology</topic><topic>Calcium Signaling - physiology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Norepinephrine</topic><topic>Wakefulness - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Åbjørsbråten, Knut Sindre</creatorcontrib><creatorcontrib>Skaaraas, Gry H E Syverstad</creatorcontrib><creatorcontrib>Cunen, Céline</creatorcontrib><creatorcontrib>Bjørnstad, Daniel M</creatorcontrib><creatorcontrib>Binder, Kristin M Gullestad</creatorcontrib><creatorcontrib>Bojarskaite, Laura</creatorcontrib><creatorcontrib>Jensen, Vidar</creatorcontrib><creatorcontrib>Nilsson, Lars N G</creatorcontrib><creatorcontrib>Rao, Shreyas B</creatorcontrib><creatorcontrib>Tang, Wannan</creatorcontrib><creatorcontrib>Hermansen, Gudmund Horn</creatorcontrib><creatorcontrib>Nagelhus, Erlend A</creatorcontrib><creatorcontrib>Ottersen, Ole Petter</creatorcontrib><creatorcontrib>Torp, Reidun</creatorcontrib><creatorcontrib>Enger, Rune</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>eLife</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Åbjørsbråten, Knut Sindre</au><au>Skaaraas, Gry H E Syverstad</au><au>Cunen, Céline</au><au>Bjørnstad, Daniel M</au><au>Binder, Kristin M Gullestad</au><au>Bojarskaite, Laura</au><au>Jensen, Vidar</au><au>Nilsson, Lars N G</au><au>Rao, Shreyas B</au><au>Tang, Wannan</au><au>Hermansen, Gudmund Horn</au><au>Nagelhus, Erlend A</au><au>Ottersen, Ole Petter</au><au>Torp, Reidun</au><au>Enger, Rune</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired astrocytic Ca 2+ signaling in awake-behaving Alzheimer's disease transgenic mice</atitle><jtitle>eLife</jtitle><addtitle>Elife</addtitle><date>2022-07-14</date><risdate>2022</risdate><volume>11</volume><eissn>2050-084X</eissn><abstract>Increased astrocytic Ca
signaling has been shown in Alzheimer's disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca
signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca
signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca
response to locomotion and an uncoupling of pupil responses and astrocytic Ca
signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRAB
, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca
responses. Our data points to a dysfunction in the norepinephrine-astrocyte Ca
activity axis, which may account for some of the cognitive deficits observed in Alzheimer's disease.</abstract><cop>England</cop><pmid>35833623</pmid><doi>10.7554/eLife.75055</doi><orcidid>https://orcid.org/0000-0001-9418-7117</orcidid></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Alzheimer Disease - genetics Animals Astrocytes - physiology Calcium Signaling - physiology Mice Mice, Transgenic Norepinephrine Wakefulness - physiology |
| title | Impaired astrocytic Ca 2+ signaling in awake-behaving Alzheimer's disease transgenic mice |
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