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Effect of fluoxetine on proliferation and/or survival of microglia and oligodendrocyte progenitor cells in the fornix and corpus callosum of the mouse brain

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Abstract

Background

Fluoxetine is one of the most widely prescribed antidepressants and a selective inhibitor of presynaptic 5-HT transporters. The fornix is the commissural and projection fiber that transmits signals from the hippocampus to other parts of the brain and opposite site of hippocampus. The corpus callosum (CC) is the largest of the commissural fibers that link the cerebral cortex of the left and right cerebral hemispheres. These brain regions play pivotal roles in cognitive functions, and functional abnormalities in these regions have been implicated in the development of various brain diseases. The purpose of the present study was to investigate the effects of fluoxetine on the proliferation and/or survival of microglia and oligodendrocyte progenitor cells (OPCs) in the fornix and CC, the white matter connecting cortical–limbic system, of the adult mouse brain.

Methods

The effects of fluoxetine on the proliferation and/or survival of microglia and OPCs were examined in lipopolysaccharide (LPS)-treated and normal mice. Proliferating cells were detected in mice that drank water containing the thymidine analog, bromodeoxyuridine (BrdU), using immunohistochemistry.

Result

Fluoxetine significantly attenuated LPS-induced increases in the number of BrdU-labeled microglia and morphological activation from the ramified to ameboid shape, and decreased the number of BrdU-labeled OPCs under basal conditions.

Conclusions

The present results indicate that fluoxetine exerts inhibitory effects on LPS-induced increases in the proliferation and/or survival and morphological activation of microglia and basal proliferation and/or survival of OPCs in the fornix and CC of adult mice.

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Abbreviations

BrdU:

Bromodeoxyuridine

CC:

Corpus callosum

LPS:

Lipopolysaccharide

MS:

Multiple sclerosis

OPCs:

Oligodendrocyte progenitor cells

PBS:

Phosphate-buffered saline

PBST:

PBS containing 0.3% Triton X-100

PFA:

Paraformaldehyde

vhc:

Ventral hippocampal commissure

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Funding

This work was supported in part by Scientific Research Grants from the Japan Society for the Promotion of Science (No. 16K07027, 19K06921).

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Authors and Affiliations

  1. Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan

    Shohei Fukushima, Erkin Kurganov, Daishi Hiratsuka & Seiji Miyata

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  1. Shohei Fukushima
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  2. Erkin Kurganov
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  3. Daishi Hiratsuka
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  4. Seiji Miyata
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Correspondence to Seiji Miyata.

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Fukushima, S., Kurganov, E., Hiratsuka, D. et al. Effect of fluoxetine on proliferation and/or survival of microglia and oligodendrocyte progenitor cells in the fornix and corpus callosum of the mouse brain. Pharmacol. Rep 72, 340–349 (2020). https://doi.org/10.1007/s43440-020-00079-1

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