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KLF4 Exerts Sedative Effects in Pentobarbital-Treated Mice

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Abstract

KLF4 is a zinc-finger transcription factor that plays an essential role in many biological processes, including neuroinflammation, neuron regeneration, cell proliferation, and apoptosis. Through effects on these processes, KLF4 has likely roles in Alzheimer’s disease, Parkinson’s disease, and traumatic brain injury. However, little is known about the role of KLF4 in more immediate behavioral processes that similarly depend upon broad changes in brain excitability, such as the sleep process. Here, behavioral approaches, western blot, and immunohistochemical experiments were used to explore the role of KLF4 on sedation and the potential mechanisms of those effects. The results showed that overexpression of KLF4 prolonged loss of righting reflex (LORR) duration in pentobarbital-treated mice and increased c-Fos expression in the lateral hypothalamus (LH) and the ventrolateral preoptic nucleus (VLPO), while it decreased c-Fos expression in the tuberomammillary nucleus (TMN). Moreover, overexpression of KLF4 reduced the expression of p53 in the hypothalamus and increased the expression of STAT3 in the hypothalamus. Therefore, these results suggest that KLF4 exerts sedative effects through the regulation of p53 and STAT3 expression, and it indicates a role of KLF4 ligands in the treatment of sleep disorders.

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Abbreviations

LH:

lateral hypothalamic

VLPO:

ventrolateral preoptic nucleus

TMN:

tuberomammillary nucleus

KET:

ketamine

MDZ:

midazolam

CH:

chloral hydrate

PENT:

pentobarbital sodium

ARC:

hypothalamic arcuate nucleus

Orx:

orexin neuron

MCH:

melanin-concentrating hormones

PVN:

paraventricular

SON:

supraoptic

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Funding

This work was supported by the Natural Science Foundation of China (Grant numbers: 81871070, 31971078 and 81971276), the National Key Research and Development Program of China (2018YFC1311603) and Jilin Science and Technology Agency funds in China (Grant numbers: 20200301005RQ; 20190701078GH; 20200201465JC; 20180101114JC) and Jilin Province Medical and Health Talents (Grant numbers: 2019SCZT013; 20170414034GH; 20190504; 2017F012).

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  1. Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, People’s Republic of China

    Ziqian Cheng, Wei Yang, Bingjin Li & Ranji Cui

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  1. Ziqian Cheng
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  2. Wei Yang
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  3. Bingjin Li
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  4. Ranji Cui
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BJL and RJC designed the research; ZQC performed the research and wrote the paper; BJL, WY, and RJC provided the critical revisions. All authors read and approved the final manuscript.

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Correspondence to Bingjin Li or Ranji Cui.

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Cheng, Z., Yang, W., Li, B. et al. KLF4 Exerts Sedative Effects in Pentobarbital-Treated Mice. J Mol Neurosci 71, 596–606 (2021). https://doi.org/10.1007/s12031-020-01680-y

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