Knockdown of long non-coding RNA SOX2OT downregulates SOX2 to improve hippocampal neurogenesis and cognitive function in a mouse model of sepsis-associated encephalopathy.
Animals
Cognition
/ physiology
Disease Models, Animal
Doublecortin Protein
Down-Regulation
/ physiology
Gene Knockdown Techniques
/ methods
Hippocampus
/ cytology
Male
Mice
Mice, Inbred C57BL
Neurogenesis
/ physiology
RNA, Long Noncoding
/ antagonists & inhibitors
Sepsis-Associated Encephalopathy
/ genetics
Cognitive dysfunction
Hippocampal neurogenesis
SOX2
SOX2OT
Sepsis-associated encephalopathy
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
25 Oct 2020
25 Oct 2020
Historique:
received:
17
04
2020
accepted:
28
09
2020
entrez:
26
10
2020
pubmed:
27
10
2020
medline:
20
8
2021
Statut:
epublish
Résumé
Aberrant hippocampal neurogenesis is an important pathological feature of sepsis-associated encephalopathy. In the current study, we examined the potential role of the long noncoding RNA (lncRNA) sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2OT), a known regulator of adult neurogenesis in sepsis-induced deficits in hippocampal neurogenesis and cognitive function. Sepsis was induced in adult C57BL/6 J male mice by cecal ligation and perforation (CLP) surgery. Randomly selected CLP mice were transfected with short interfering RNAs (siRNAs) against SOX2OT or SOX2, or with scrambled control siRNA. Cognitive behavior was tested 8-12 days post-surgery using a Morris water maze. Western blotting and RT-qPCR were used to determine expression of SOX2, Ki67, doublecortin (DCX), nestin, brain lipid-binding protein, and glial fibrillary acidic protein (GFAP) in the hippocampus. The number of bromodeoxyuridine (BrdU) CLP mice showed progressive increases in SOX2OT and SOX2 mRNA levels on days 3, 7, and 14 after CLP surgery, accompanied by impaired cognitive function. Sepsis led to decrease in all neuronal markers in the hippocampus, except GFAP. Immunofluorescence confirmed the decreased numbers of BrdU SOX2OT knockdown improves sepsis-induced deficits in hippocampal neurogenesis and cognitive function by downregulating SOX2 in mice. Inhibiting SOX2OT/SOX2 signaling may be effective for treating or preventing neurodegeneration in sepsis-associated encephalopathy.
Sections du résumé
BACKGROUND
BACKGROUND
Aberrant hippocampal neurogenesis is an important pathological feature of sepsis-associated encephalopathy. In the current study, we examined the potential role of the long noncoding RNA (lncRNA) sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2OT), a known regulator of adult neurogenesis in sepsis-induced deficits in hippocampal neurogenesis and cognitive function.
METHODS
METHODS
Sepsis was induced in adult C57BL/6 J male mice by cecal ligation and perforation (CLP) surgery. Randomly selected CLP mice were transfected with short interfering RNAs (siRNAs) against SOX2OT or SOX2, or with scrambled control siRNA. Cognitive behavior was tested 8-12 days post-surgery using a Morris water maze. Western blotting and RT-qPCR were used to determine expression of SOX2, Ki67, doublecortin (DCX), nestin, brain lipid-binding protein, and glial fibrillary acidic protein (GFAP) in the hippocampus. The number of bromodeoxyuridine (BrdU)
RESULTS
RESULTS
CLP mice showed progressive increases in SOX2OT and SOX2 mRNA levels on days 3, 7, and 14 after CLP surgery, accompanied by impaired cognitive function. Sepsis led to decrease in all neuronal markers in the hippocampus, except GFAP. Immunofluorescence confirmed the decreased numbers of BrdU
CONCLUSION
CONCLUSIONS
SOX2OT knockdown improves sepsis-induced deficits in hippocampal neurogenesis and cognitive function by downregulating SOX2 in mice. Inhibiting SOX2OT/SOX2 signaling may be effective for treating or preventing neurodegeneration in sepsis-associated encephalopathy.
Identifiants
pubmed: 33100215
doi: 10.1186/s12974-020-01970-7
pii: 10.1186/s12974-020-01970-7
pmc: PMC7586681
doi:
Substances chimiques
Dcx protein, mouse
0
Doublecortin Protein
0
RNA, Long Noncoding
0
long noncoding RNA Sox2OT, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
320Subventions
Organisme : National Natural Science Foundation of China
ID : 81873954
Organisme : National Natural Science Foundation of China
ID : 81971872
Organisme : Nanjing Medical Science and Technical Development Foundation
ID : QRX17019
Organisme : Nanjing Medical Science and Technical Development Foundation
ID : YKK18105
Organisme : Six Talent Climax Foundation of Jiangsu
ID : WSW-106
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