Russo, E;
Leo, A;
Crupi, R;
Aiello, R;
Lippiello, P;
Spiga, R;
Chimirri, S;
... De Sarro, G; + view all
(2016)
Everolimus improves memory and learning while worsening depressive- and anxiety-like behavior in an animal model of depression.
Journal of Psychiatric Research
, 78
pp. 1-10.
10.1016/j.jpsychires.2016.03.008.
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Abstract
Everolimus (EVR) is an orally-administered rapamycin analog that selectively inhibits the mammalian target of rapamycin (mTOR) kinase (mainly mTORC1 and likely mTORC2) and the related signaling pathway. mTOR is a serine/threonine protein kinase regulating multiple important cellular functions; dysfunction of mTOR signaling has also been implicated in the pathophysiology of several neurological, neurodegenerative, developmental and cognitive disorders. EVR is widely used as an anti-neoplastic therapy and more recently in children with tuberous sclerosis complex (TSC). However, no clear correlation exists between EVR use and development of central side effects e.g. depression, anxiety or cognitive impairment. We studied the effects of a 3 weeks administration of EVR in mice chronically treated with betamethasone 21-phosphate disodium (BTM) as a model of depression and cognitive decline. EVR treatment had detrimental effects on depressive- and anxiety-like behavior while improving cognitive performance in both control (untreated) and BTM-treated mice. Such effects were accompanied by an increased hippocampal neurogenesis and synaptogenesis. Our results therefore might support the proposed pathological role of mTOR dysregulation in depressive disorders and confirm some previous data on the positive effects of mTOR inhibition in cognitive decline. We also show that EVR, possibly through mTOR inhibition, may be linked to the development of anxiety. The increased hippocampal neurogenesis by EVR might explain its ability to improve cognitive function or protect from cognitive decline. Our findings suggest some caution in the use of EVR, particularly in the developing brain; patients should be carefully monitored for their psychiatric/neurological profiles in any clinical situation where an mTOR inhibitor and in particular EVR is used e.g. cancer treatment, TSC or immunosuppression.
| Type: | Article |
|---|---|
| Title: | Everolimus improves memory and learning while worsening depressive- and anxiety-like behavior in an animal model of depression |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jpsychires.2016.03.008 |
| Publisher version: | http://dx.doi.org/10.1016/j.jpsychires.2016.03.008 |
| Language: | English |
| Additional information: | Copyright © The authors. Article made available under a Creative Commons license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Published by Elsevier Ltd and available on the journal website at http://dx.doi.org/10.1016/j.jpsychires.2016.03.008 |
| Keywords: | Depression, Anxiety, Cognitive function, mTOR, Neurogenesis, Mice |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1478346 |
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