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Previous reports have also signified that spironolactone has anti-inflammatory effects.Therefore, the aim of this study was to assess the modulatory effects of spironolactone onneuroinflammation and memory loss in a rat model of AD.Methods: The \u03b2-amyloid protein fragment 25-35 (A\u03b2) was injected in the dorsal hippocampus (5\u03bcg\/2.5 \u03bcL each side) of male Sprague-Dawley rats for four consecutive days to induce memoryimpairment. Animals have intraperitoneally received spironolactone (10, 25, or 50 mg\/kg, N = 6\/group) or vehicle for 14 days. The passive inhibitory avoidance and the novel recognition testswere used for memory evaluation. Neuroinflammation was assessed by measuring the level ofIba1 protein, a marker of microglial activation, using western immunoblotting.Results: Different doses of spironolactone showed no significant changes in latency times anddiscriminations ratios in passive inhibitory avoidance and novel recognition tests, respectively,as compared to vehicle. However, spironolactone-treated groups showed significantly lowerIba1 protein levels in comparison to the vehicle-treated group (P &lt; 0.01).Conclusion: Spironolactone had a modulatory effect on neuroinflammation through a repressiveeffect on microglial activation with no valuable effect on memory improvement in a rat modelof AD. The findings of this study suggest that A\u03b2-induced memory loss may not be directly linkedto microglial activation. Spironolactone may be a potential candidate to be examined in otherneuroinflammatory disorders.<\/jats:p>","DOI":"10.34172\/apb.2022.065","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T07:38:59Z","timestamp":1634801939000},"page":"623-631","update-policy":"https:\/\/doi.org\/10.34172\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Effect of Spironolactone on \u03b2-amyloid-Induced Memory Impairment in Male Rats: The Role of Microglial Inhibition"],"prefix":"10.34172","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8581-1977","authenticated-orcid":true,"given":"Mohammad","family":"Mehdipour","sequence":"first","affiliation":[{"name":"Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, 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