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doi:10.22028/D291-41168
Titel: | Specific detection and deletion of the sigma-1 receptor widely expressed in neurons and glial cells in vivo |
VerfasserIn: | Liu, Qing Guo, Qilin Fang, Li-Pao Yao, Honghong Scheller, Anja Kirchhoff, Frank Huang, Wenhui |
Sprache: | Englisch |
Titel: | Journal of Neurochemistry |
Bandnummer: | 164 (2023) |
Heft: | 6 |
Seiten: | 764-785 |
Verlag/Plattform: | Wiley |
Erscheinungsjahr: | 2022 |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | The chaperon protein sigma-1 receptor (S1R) has been discovered over 40 years ago. Recent pharmacological studies using S1R exogenous ligands demonstrated a promising therapeutical potential of targeting the S1R in several neurological disorders. Although intensive in vitro studies have revealed S1Rs are mainly residing at the membrane of the endoplasmic reticulum (ER), the cell-specific in vivo expression pattern of S1Rs is still unclear, mainly because of the lack of a reliable detection method which also prevented a comprehensive functional analysis. Here, first, we identified a highly specific antibody using S1R knockout (KO) mice and established an immunohistochemical protocol involving a 1% sodium dodecyl sulphate (SDS) antigen retrieval step. Second, we characterized the S1R expression in the mouse brain and can demonstrate that the S1R is widely expressed: in principal neurons, interneurons and all glial cell types. In addition, unlike reported in previous studies, we showed that the S1R expression in astrocytes is not colocalized with the astrocytic cytoskeleton protein GFAP. Thus, our results raise concerns over previously reported S1R properties. Finally, we generated a Credependent S1R conditional KO mouse (S1R flox) to study cell-type-specific functions of the S1R. As a proof of concept, we successfully ablated S1R expressions in neurons or microglia employing neuronal and microglial Cre-expressing mice, respectively. In summary, we provide powerful tools to cell-specifically detect, delete and functionally characterize S1R in vivo. |
DOI der Erstveröffentlichung: | 10.1111/jnc.15693 |
URL der Erstveröffentlichung: | https://doi.org/10.1111/jnc.15693 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-411680 hdl:20.500.11880/36940 http://dx.doi.org/10.22028/D291-41168 |
ISSN: | 1471-4159 0022-3042 |
Datum des Eintrags: | 24-Nov-2023 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting Information |
In Beziehung stehendes Objekt: | https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fjnc.15693&file=jnc15693-sup-0001-Figures.pdf |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Physiologie |
Professur: | M - Prof. Dr. Frank Kirchhoff |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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Journal of Neurochemistry - 2022 - Liu - Specific detection and deletion of the sigma‐1 receptor widely expressed in.pdf | 20,42 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons