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10.3390/cells11132002
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Article

Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice

by
Keerthana Chithanathan
1,
Kelli Somelar
2,
Monika Jürgenson
2,
Tamara Žarkovskaja
2,
Kapilraj Periyasamy
3,
Ling Yan
1,
Nathaniel Magilnick
4,
Mark P. Boldin
4,
Ana Rebane
3,
Li Tian
1 and
Alexander Zharkovsky
2,*
1
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, Estonia
2
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, Estonia
3
Department of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, Estonia
4
Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA 91010, USA
*
Author to whom correspondence should be addressed.
Cells 2022, 11(13), 2002; https://doi.org/10.3390/cells11132002
Submission received: 1 June 2022 / Revised: 16 June 2022 / Accepted: 20 June 2022 / Published: 22 June 2022
(This article belongs to the Special Issue Induced Impairment of Neurogenesis and Brain Diseases)
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Abstract

The miR-146 family consists of two microRNAs (miRNAs), miR-146a and miR-146b, which are both known to suppress a variety of immune responses. Here in this study, we show that miR-146b is abundantly expressed in neuronal cells, while miR-146a is mainly expressed in microglia and astroglia of adult mice. Accordingly, miR-146b deficient (Mir146b-/-) mice exhibited anxiety-like behaviors and enhanced cognition. Characterization of cellular composition of Mir146b-/- mice using flow cytometry revealed an increased number of neurons and a decreased abundancy of astroglia in the hippocampus and frontal cortex, whereas microglia abundancy remained unchanged. Immunohistochemistry showed a higher density of neurons in the frontal cortex of Mir146b-/- mice, enhanced hippocampal neurogenesis as evidenced by an increased proliferation, and survival of newly generated cells with enhanced maturation into neuronal phenotype. No microglial activation or signs of neuroinflammation were observed in Mir146b-/- mice. Further analysis demonstrated that miR-146b deficiency is associated with elevated expression of glial cell line-derived neurotrophic factor (Gdnf) mRNA in the hippocampus, which might be at least in part responsible for the observed neuronal expansion and the behavioral phenotype. This hypothesis is partially supported by the positive correlation between performance of mice in the object recognition test and Gdnf mRNA expression in Mir146b-/- mice. Together, these results show the distinct function of miR-146b in controlling behaviors and provide new insights in understanding cell-specific function of miR-146b in the neuronal and astroglial organization of the mouse brain.
Keywords: miR-146b; cognition; anxiety; astrocytes; microglia; neurogenesis; neuronal development; Gdnf miR-146b; cognition; anxiety; astrocytes; microglia; neurogenesis; neuronal development; Gdnf

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MDPI and ACS Style

Chithanathan, K.; Somelar, K.; Jürgenson, M.; Žarkovskaja, T.; Periyasamy, K.; Yan, L.; Magilnick, N.; Boldin, M.P.; Rebane, A.; Tian, L.; et al. Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice. Cells 2022, 11, 2002. https://doi.org/10.3390/cells11132002

AMA Style

Chithanathan K, Somelar K, Jürgenson M, Žarkovskaja T, Periyasamy K, Yan L, Magilnick N, Boldin MP, Rebane A, Tian L, et al. Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice. Cells. 2022; 11(13):2002. https://doi.org/10.3390/cells11132002

Chicago/Turabian Style

Chithanathan, Keerthana, Kelli Somelar, Monika Jürgenson, Tamara Žarkovskaja, Kapilraj Periyasamy, Ling Yan, Nathaniel Magilnick, Mark P. Boldin, Ana Rebane, Li Tian, and et al. 2022. "Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice" Cells 11, no. 13: 2002. https://doi.org/10.3390/cells11132002

APA Style

Chithanathan, K., Somelar, K., Jürgenson, M., Žarkovskaja, T., Periyasamy, K., Yan, L., Magilnick, N., Boldin, M. P., Rebane, A., Tian, L., & Zharkovsky, A. (2022). Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice. Cells, 11(13), 2002. https://doi.org/10.3390/cells11132002

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