Signatures of the Consolidated Response of Astrocytes to Ischemic Factors In Vitro
Whether and under what conditions astrocytes can mount a collective network response has recently become one of the central questions in neurobiology. Here, we address this problem, investigating astrocytic reactions to different biochemical stimuli and ischemic-like conditions in vitro. Identifying...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/21/7952 |
| _version_ | 1797549758778179584 |
|---|---|
| author | Elena V. Mitroshina Mikhail I. Krivonosov Dmitriy E. Burmistrov Maria O. Savyuk Tatiana A. Mishchenko Mikhail V. Ivanchenko Maria V. Vedunova |
| author_facet | Elena V. Mitroshina Mikhail I. Krivonosov Dmitriy E. Burmistrov Maria O. Savyuk Tatiana A. Mishchenko Mikhail V. Ivanchenko Maria V. Vedunova |
| author_sort | Elena V. Mitroshina |
| collection | DOAJ |
| description | Whether and under what conditions astrocytes can mount a collective network response has recently become one of the central questions in neurobiology. Here, we address this problem, investigating astrocytic reactions to different biochemical stimuli and ischemic-like conditions in vitro. Identifying an emergent astrocytic network is based on a novel mathematical approach that extracts calcium activity from time-lapse fluorescence imaging and estimates the connectivity of astrocytes. The developed algorithm represents the astrocytic network as an oriented graph in which the nodes correspond to separate astrocytes, and the edges indicate high dynamical correlations between astrocytic events. We demonstrate that ischemic-like conditions decrease network connectivity in primary cultures in vitro, although calcium events persist. Importantly, we found that stimulation under normal conditions with 10 µM ATP increases the number of long-range connections and the degree of corresponding correlations in calcium activity, apart from the frequency of calcium events. This result indicates that astrocytes can form a large functional network in response to certain stimuli. In the post-ischemic interval, the response to ATP stimulation is not manifested, which suggests a deep lesion in functional astrocytic networks. The blockade of Connexin 43 during ischemic modeling preserves the connectivity of astrocytes in the post-hypoxic period. |
| first_indexed | 2024-03-10T15:19:58Z |
| format | Article |
| id | doaj.art-a76a9fbdfcfd4049af81ad6b0845ae11 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:19:58Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a76a9fbdfcfd4049af81ad6b0845ae112023-11-20T18:37:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121795210.3390/ijms21217952Signatures of the Consolidated Response of Astrocytes to Ischemic Factors In VitroElena V. Mitroshina0Mikhail I. Krivonosov1Dmitriy E. Burmistrov2Maria O. Savyuk3Tatiana A. Mishchenko4Mikhail V. Ivanchenko5Maria V. Vedunova6Institute of Biology and Biomedicine, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, RussiaInstitute of Information, Technology, Mathematics and Mechanics, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, RussiaInstitute of Biology and Biomedicine, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, RussiaInstitute of Biology and Biomedicine, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, RussiaInstitute of Biology and Biomedicine, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, RussiaInstitute of Information, Technology, Mathematics and Mechanics, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, RussiaInstitute of Biology and Biomedicine, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, RussiaWhether and under what conditions astrocytes can mount a collective network response has recently become one of the central questions in neurobiology. Here, we address this problem, investigating astrocytic reactions to different biochemical stimuli and ischemic-like conditions in vitro. Identifying an emergent astrocytic network is based on a novel mathematical approach that extracts calcium activity from time-lapse fluorescence imaging and estimates the connectivity of astrocytes. The developed algorithm represents the astrocytic network as an oriented graph in which the nodes correspond to separate astrocytes, and the edges indicate high dynamical correlations between astrocytic events. We demonstrate that ischemic-like conditions decrease network connectivity in primary cultures in vitro, although calcium events persist. Importantly, we found that stimulation under normal conditions with 10 µM ATP increases the number of long-range connections and the degree of corresponding correlations in calcium activity, apart from the frequency of calcium events. This result indicates that astrocytes can form a large functional network in response to certain stimuli. In the post-ischemic interval, the response to ATP stimulation is not manifested, which suggests a deep lesion in functional astrocytic networks. The blockade of Connexin 43 during ischemic modeling preserves the connectivity of astrocytes in the post-hypoxic period.https://www.mdpi.com/1422-0067/21/21/7952astrocytesastrocytic networksischemiaconnexin 43calcium activity |
| spellingShingle | Elena V. Mitroshina Mikhail I. Krivonosov Dmitriy E. Burmistrov Maria O. Savyuk Tatiana A. Mishchenko Mikhail V. Ivanchenko Maria V. Vedunova Signatures of the Consolidated Response of Astrocytes to Ischemic Factors In Vitro International Journal of Molecular Sciences astrocytes astrocytic networks ischemia connexin 43 calcium activity |
| title | Signatures of the Consolidated Response of Astrocytes to Ischemic Factors In Vitro |
| title_full | Signatures of the Consolidated Response of Astrocytes to Ischemic Factors In Vitro |
| title_fullStr | Signatures of the Consolidated Response of Astrocytes to Ischemic Factors In Vitro |
| title_full_unstemmed | Signatures of the Consolidated Response of Astrocytes to Ischemic Factors In Vitro |
| title_short | Signatures of the Consolidated Response of Astrocytes to Ischemic Factors In Vitro |
| title_sort | signatures of the consolidated response of astrocytes to ischemic factors in vitro |
| topic | astrocytes astrocytic networks ischemia connexin 43 calcium activity |
| url | https://www.mdpi.com/1422-0067/21/21/7952 |
| work_keys_str_mv | AT elenavmitroshina signaturesoftheconsolidatedresponseofastrocytestoischemicfactorsinvitro AT mikhailikrivonosov signaturesoftheconsolidatedresponseofastrocytestoischemicfactorsinvitro AT dmitriyeburmistrov signaturesoftheconsolidatedresponseofastrocytestoischemicfactorsinvitro AT mariaosavyuk signaturesoftheconsolidatedresponseofastrocytestoischemicfactorsinvitro AT tatianaamishchenko signaturesoftheconsolidatedresponseofastrocytestoischemicfactorsinvitro AT mikhailvivanchenko signaturesoftheconsolidatedresponseofastrocytestoischemicfactorsinvitro AT mariavvedunova signaturesoftheconsolidatedresponseofastrocytestoischemicfactorsinvitro |