Jens Randel Nyengaard

The rat hippocampal gliovascular system following one week vortioxetine and fluoxetine

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The rat hippocampal gliovascular system following one week vortioxetine and fluoxetine. / Chen, Fenghua; Danladi, Jibrin; Ardalan, Maryam; Nyengaard, Jens Randel; Sánchez, Connie; Wegener, Gregers.

In: European Neuropsychopharmacology, Vol. 42, 01.2021, p. 45-56.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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@article{637d8c5b95fa41f5a58d99f63f8eef7d,
title = "The rat hippocampal gliovascular system following one week vortioxetine and fluoxetine",
abstract = "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.",
keywords = "Astrocytes, Microglia, Vortioxetine",
author = "Fenghua Chen and Jibrin Danladi and Maryam Ardalan and Nyengaard, {Jens Randel} and Connie S{\'a}nchez and Gregers Wegener",
note = "Publisher Copyright: {\textcopyright} 2020 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jan,
doi = "10.1016/j.euroneuro.2020.11.008",
language = "English",
volume = "42",
pages = "45--56",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - The rat hippocampal gliovascular system following one week vortioxetine and fluoxetine

AU - Chen, Fenghua

AU - Danladi, Jibrin

AU - Ardalan, Maryam

AU - Nyengaard, Jens Randel

AU - Sánchez, Connie

AU - Wegener, Gregers

N1 - Publisher Copyright: © 2020 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

KW - Astrocytes

KW - Microglia

KW - Vortioxetine

UR - http://www.scopus.com/inward/record.url?scp=85096173546&partnerID=8YFLogxK

U2 - 10.1016/j.euroneuro.2020.11.008

DO - 10.1016/j.euroneuro.2020.11.008

M3 - Journal article

C2 - 33199100

VL - 42

SP - 45

EP - 56

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

ER -