ArticleJournal of neuroinflammation2014
Estrogen receptor alpha deficiency protects against development of cognitive impairment in murine lupus.
Article in Journal of neuroinflammation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Progress in the Pathogenesis and Treatment of Neuropsychiatric Systemic Lupus Erythematosus.Journal of clinical medicine · 2022Review
- Lupus-prone B6.Nba2 male and female mice display anti-DWEYS reactivity and a neuropsychiatric phenotype.Brain, behavior, and immunity · 2021Article
- Article
- Preconditioning with CpG-ODN1826 reduces ischemic brain injury in young male mice: a replication study.Conditioning medicine · 2019Article
- Estrogen receptor alpha promotes lupus in (NZB×NZW)F1 mice in a B cell intrinsic manner.Clinical immunology (Orlando, Fla.) · 2017Article
- Estrogens, Neuroinflammation, and Neurodegeneration.Endocrine reviews · 2016Review
- The Role of Steroid Hormones in the Modulation of Neuroinflammation by Dietary Interventions.Frontiers in endocrinology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOne of the more profound features of systemic lupus erythematosus (SLE) is that females have a 9:1 prevalence of this disease over males. Up to 80% of SLE patients have cognitive defects or affective disorders. The mechanism of CNS injury responsible for cognitive impairment is unknown. We previously showed that ERα deficiency significantly reduced renal disease and increased survival in lupus-prone mice. We hypothesized that ERα deficiency would be similarly protective in the brain, and that ERα may play a role in modulating blood-brain barrier (BBB) integrity and/or neuroinflammation in lupus-prone mice.
methodsMRL/lpr ERα+/+ and ERαKO mice (n = 46) were ovariectomized, received 17β-estradiol pellets, and underwent radial arm water maze (WRAM) and novel object recognition (NOR) testing starting at eight weeks of age. Mice were sacrificed and brains were hemisected and processed for either immunohistochemistry, or hippocampus and parietal cortex dissection for Western blotting.
resultsMRL/lpr ERαKO mice (n = 21) performed significantly better in WRAM testing than wild-type MRL/lpr mice (n = 25). There was a significant reduction in reference memory errors (P <0.007), working memory errors (P <0.05), and start arm errors (P <0.02) in ERαKO mice. There were significant differences in NOR testing, particularly total exploration time, with ERα deficiency normalizing behavior. No significant differences were seen in markers of tight junction, astrogliosis, or microgliosis in the hippocampus or cortex by Western blot, however, there was a significant reduction in numbers of Iba1+ activated microglia in the hippocampus of ERαKO mice, as evidenced by immunohistochemietry (IHC).
conclusionERα deficiency provides significant protection against cognitive deficits in MRL/lpr mice as early as eight weeks of age. Additionally, the significant reduction in Iba1+ activated microglia in the MRL/lpr ERαKO mice was consistent with reduced inflammation, and may represent a biological mechanism for the cognitive improvement observed.
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Registered trials
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