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Much remains unknown about the relationship between vitamin D deficiency (VDD), stress\u2010induced cognitive dysfunctions and depressive\u2010like behaviour. In this study, 4\u2010month\u2010old male C57Bl\/6J mice were fed with control or vitamin D free diet for 6\u2009months, followed by unpredictable chronic stress (UCMS) for 8\u2009weeks. VDD induced cognitive impairment and reduced grooming behaviour, but did not induce depressive\u2010like behaviour. While UCMS in vitamin D sufficient mice induced expected depressive\u2010like phenotype and impairments in the contextual fear memory, chronic stress did not manifest as an additional risk factor for memory impairments and depressive\u2010like behaviour in VDD mice. In fact, UCMS restored self\u2010care behaviour in VDD mice. At the histopathological level, VDD mice exhibited cell loss in the granule cell layer, reduced survival of newly generated cells, accompanied with an increased number of apoptotic cells and alterations in glial morphology in the hippocampus; however, these effects were not exacerbated by UCMS. Interestingly, UCMS reversed VDD induced loss of microglial cells. Moreover, tyrosine hydroxylase levels decreased in the striatum of VDD mice, but not in stressed VDD mice. These findings indicate that long\u2010term VDD in adulthood impairs cognition but does not augment behavioural response to UCMS in middle\u2010aged mice. While VDD caused cell loss and altered glial response in the DG of the hippocampus, these effects were not exacerbated by UCMS and could contribute to mechanisms regulating altered stress response.<\/jats:p>","DOI":"10.1111\/ejn.16256","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T05:42:23Z","timestamp":1706161343000},"page":"1696-1722","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["\u2018Unpredictable chronic mild stress does not exacerbate memory impairment or altered neuronal and glial plasticity in the hippocampus of middle\u2010aged vitamin D deficient mice\u2019"],"prefix":"10.1111","volume":"59","author":[{"given":"Kelli","family":"Somelar\u2010Duracz","sequence":"first","affiliation":[{"name":"Institute of Biomedicine and Translational Medicine, Department of Pharmacology University of Tartu  Tartu 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