17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection
Abstract Urinary tract infections (UTIs) are common and frequently precipitate delirium-like states. Advanced age coincident with the postmenopausal period is a risk factor for delirium following UTIs. We previously demonstrated a pathological role for interleukin-6 (IL-6) in mediating delirium-like...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24247-w |
| _version_ | 1811319289621250048 |
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| author | Gena Guidry Nicklaus A. Sparrow Hyyat S. Marshall Roberta De Souza Santos Suman P. Bharath Michael M. Gezalian Margareta D. Pisarska Jean-Philippe Vit Scott A. Kelly S. Ananth Karumanchi Shouri Lahiri |
| author_facet | Gena Guidry Nicklaus A. Sparrow Hyyat S. Marshall Roberta De Souza Santos Suman P. Bharath Michael M. Gezalian Margareta D. Pisarska Jean-Philippe Vit Scott A. Kelly S. Ananth Karumanchi Shouri Lahiri |
| author_sort | Gena Guidry |
| collection | DOAJ |
| description | Abstract Urinary tract infections (UTIs) are common and frequently precipitate delirium-like states. Advanced age coincident with the postmenopausal period is a risk factor for delirium following UTIs. We previously demonstrated a pathological role for interleukin-6 (IL-6) in mediating delirium-like phenotypes in a murine model of UTI. Estrogen has been implicated in reducing peripheral IL-6 expression, but it is unknown whether the increased susceptibility of postmenopausal females to developing delirium concomitant with UTIs reflects diminished effects of circulating estrogen. Here, we tested this hypothesis in a mouse model of UTI. Female C57BL/6J mice were oophorectomized, UTIs induced by transurethral inoculation of E. coli, and treated with 17β-estradiol. Delirium-like behaviors were evaluated prior to and following UTI and 17β-estradiol treatment. Compared to controls, mice treated with 17β-estradiol had less neuronal injury, improved delirium-like behaviors, and less plasma and frontal cortex IL-6. In vitro studies further showed that 17β-estradiol may also directly mediate neuronal protection, suggesting pleiotropic mechanisms of 17β-estradiol-mediated neuroprotection. In summary, we demonstrate a beneficial role for 17β-estradiol in ameliorating acute UTI-induced structural and functional delirium-like phenotypes. These findings provide pre-clinical justification for 17β-estradiol as a therapeutic target to ameliorate delirium following UTI. |
| first_indexed | 2024-04-13T12:40:10Z |
| format | Article |
| id | doaj.art-757169c0da244f42bd6bf2223a53515d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T12:40:10Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-757169c0da244f42bd6bf2223a53515d2022-12-22T02:46:32ZengNature PortfolioScientific Reports2045-23222022-11-0112111410.1038/s41598-022-24247-w17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infectionGena Guidry0Nicklaus A. Sparrow1Hyyat S. Marshall2Roberta De Souza Santos3Suman P. Bharath4Michael M. Gezalian5Margareta D. Pisarska6Jean-Philippe Vit7Scott A. Kelly8S. Ananth Karumanchi9Shouri Lahiri10Department of Neurology, Cedars-Sinai Medical CenterDepartment of Neurology, Cedars-Sinai Medical CenterDepartment of Neurology, Cedars-Sinai Medical CenterDepartment of Medicine, Cedars-Sinai Medical CenterDepartment of Neurology, Cedars-Sinai Medical CenterDepartment of Neurology, Cedars-Sinai Medical CenterDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical CenterDepartment of Neurosurgery, Cedars-Sinai Medical CenterDepartment of Neurology, Cedars-Sinai Medical CenterDepartment of Medicine, Cedars-Sinai Medical CenterDepartment of Neurology, Cedars-Sinai Medical CenterAbstract Urinary tract infections (UTIs) are common and frequently precipitate delirium-like states. Advanced age coincident with the postmenopausal period is a risk factor for delirium following UTIs. We previously demonstrated a pathological role for interleukin-6 (IL-6) in mediating delirium-like phenotypes in a murine model of UTI. Estrogen has been implicated in reducing peripheral IL-6 expression, but it is unknown whether the increased susceptibility of postmenopausal females to developing delirium concomitant with UTIs reflects diminished effects of circulating estrogen. Here, we tested this hypothesis in a mouse model of UTI. Female C57BL/6J mice were oophorectomized, UTIs induced by transurethral inoculation of E. coli, and treated with 17β-estradiol. Delirium-like behaviors were evaluated prior to and following UTI and 17β-estradiol treatment. Compared to controls, mice treated with 17β-estradiol had less neuronal injury, improved delirium-like behaviors, and less plasma and frontal cortex IL-6. In vitro studies further showed that 17β-estradiol may also directly mediate neuronal protection, suggesting pleiotropic mechanisms of 17β-estradiol-mediated neuroprotection. In summary, we demonstrate a beneficial role for 17β-estradiol in ameliorating acute UTI-induced structural and functional delirium-like phenotypes. These findings provide pre-clinical justification for 17β-estradiol as a therapeutic target to ameliorate delirium following UTI.https://doi.org/10.1038/s41598-022-24247-w |
| spellingShingle | Gena Guidry Nicklaus A. Sparrow Hyyat S. Marshall Roberta De Souza Santos Suman P. Bharath Michael M. Gezalian Margareta D. Pisarska Jean-Philippe Vit Scott A. Kelly S. Ananth Karumanchi Shouri Lahiri 17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection Scientific Reports |
| title | 17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection |
| title_full | 17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection |
| title_fullStr | 17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection |
| title_full_unstemmed | 17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection |
| title_short | 17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection |
| title_sort | 17β estradiol ameliorates delirium like phenotypes in a murine model of urinary tract infection |
| url | https://doi.org/10.1038/s41598-022-24247-w |
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