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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



Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons