The knockdown of trek-1 in hippocampal neurons attenuate lipopolysaccharide-induced depressive-like behavior in mice

Ajung Kim, Hyun Gug Jung, Yeong Eun Kim, Seung Chan Kim, Jae Yong Park, Seok Geun Lee, Eun Mi Hwang

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    TWIK-related potassium channel-1 (TREK-1) is broadly expressed in the brain and involved in diverse brain diseases, such as seizures, ischemia, and depression. However, the cell type-specific roles of TREK-1 in the brain are largely unknown. Here, we generated a Cre-dependent TREK-1 knockdown (Cd-TREK-1 KD) transgenic mouse containing a gene cassette for Cre-dependent TREK-1 short hairpin ribonucleic acid to regulate the cell type-specific TREK-1 expression. We confirmed the knockdown of TREK-1 by injecting adeno-associated virus (AAV) expressing Cre into the hippocampus of the mice. To study the role of hippocampal neuronal TREK-1 in a lipopolysaccharide (LPS)-induced depression model, we injected AAV-hSyn-BFP (nCTL group) or AAV-hSyn-BFP-Cre (nCre group) virus into the hippocampus of Cd-TREK-1 KD mice. Interestingly, the immobility in the tail suspension test after LPS treatment did not change in the nCre group. Additionally, some neurotrophic factors (BDNF, VEGF, and IGF-1) significantly increased more in the nCre group compared to the nCTL group after LPS treatment, but there was no difference in the expression of their receptors. Therefore, our data suggest that TREK-1 in the hippocampal neurons has antidepressant effects, and that Cd-TREK-1 KD mice are a valuable tool to reveal the cell type-specific roles of TREK-1 in the brain.

    Original languageEnglish
    Article number5902
    JournalInternational journal of molecular sciences
    Volume20
    Issue number23
    DOIs
    Publication statusPublished - 2019 Dec 1

    Bibliographical note

    Funding Information:
    This research was supported by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017M3C7A1043838, 2017M3C7A1079694, 2016M3C7A1904149).

    Funding Information:
    Funding: This research was supported by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017M3C7A1043838, 2017M3C7A1079694, 2016M3C7A1904149).

    Publisher Copyright:
    © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

    Keywords

    • Conditional knockdown
    • Depression
    • Hippocampus
    • Neurotrophic factor
    • TREK-1

    ASJC Scopus subject areas

    • Catalysis
    • Molecular Biology
    • Spectroscopy
    • Computer Science Applications
    • Physical and Theoretical Chemistry
    • Organic Chemistry
    • Inorganic Chemistry

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