The rat hippocampal gliovascular system following one week vortioxetine and fluoxetine

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We have previously reported that vortioxetine, unlike the selective serotonin reuptake inhibitor fluoxetine, produces a rapid increase of dendritic spine number and Brain Derived Neurotrophic Factor (BDNF)-associated formation of synapses with mitochondrial support in the rat hippocampal CA1 and dentate gyrus. As a continuation of this line of research, and given the putative role of brain glial cells in mediating antidepressant responses the present study investigated early effects of vortioxetine on hippocampal microvasculature and Vascular Endothelial Growth Factor (VEGF) and astrocytes and microglia cells. Rats were treated for 1 week with vortioxetine (1.6 g/kg food chow) or fluoxetine (160 mg/L drinking water) at pharmacologically relevant doses. Stereological principles were used to estimate the number of ALDH1L1 positive astrocytes and Iba1 positive microglia cells, and the length of microvessels in subregions of hippocampus. VEGF protein levels were visualized with immunohistochemistry. Our results showed that vortioxetine significantly increased the number of ramified (resting) microglia and astrocytes accompanied by VEGF level elevation, whereas fluoxetine had no effect after 7 days treatment on these measures. Our findings suggest that astrocytes and microglia may have a role in mediating the pharmacological effects of vortioxetine in rats and that these effects are mediated through mechanisms that go beyond inhibition of the serotonin transporter and may target specific 5-HT receptors. It remains to be investigated whether these findings are relevant for the therapeutic effects of vortioxetine.
OriginalsprogEngelsk
TidsskriftEuropean Neuropsychopharmacology
Vol/bind42
Sider (fra-til)45-56
Antal sider12
ISSN0924-977X
DOI
StatusUdgivet - jan. 2021

Bibliografisk note

Funding Information:
Dr. Chen report having received salary support from H. Lundbeck A/S. Dr. Dr. Nyengaard reports having received research funding from Sino-Danish Center and the Villum Foundation via Centre for Stochastic Geometry and Advanced Bioimaging. Dr. Wegener reports having received funding from Independent Research Fund Denmark (grant 8020-00310B ), Aarhus University Research Foundation , Denmark (AU-IDEAS initiative (eMOOD)), and EU Horizon 2020 (ExEDE).

Funding Information:
Dr. Chen report having received salary support from H. Lundbeck A/S. Dr. Ardalan reported having salary support from Lundbeck Foundation. Connie Sanchez was full-time employee at H. Lundbeck A/S when the study was conducted. Dr. Nyengaard reports having received research funding from Sino-Danish Center and the Villum Foundation via Centre for Stochastic Geometry and Advanced Bioimaging. Dr. Wegener reported having received lecture/consultancy fees from H. Lundbeck A/S, Servier SA, Astra Zeneca AB, Eli Lilly A/S, Sun Pharma Pty Ltd, Pfizer Inc, Shire A/S, HB Pharma A/S, Arla Foods A.m.b.A., Alkermes Inc, and Mundipharma International Ltd., and research funding from the Danish Medical Research Council, Aarhus University Research Foundation (AU-IDEAS initiative (eMOOD)), the Novo Nordisk Foundation, the Lundbeck Foundation, and EU Horizon 2020 (ExEDE). Dr. Ardalan and Danladi, reported no biomedical financial interests or potential conflicts of interest.

Funding Information:
This research was supported by H. Lundbeck A/S, Independent Research Fund Denmark (grant 8020-00310B ), Aarhus University Research Foundation ( AU-IDEAS initiative (eMOOD) ), and EU Horizon 2020 (ExEDE).

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