Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice
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 mi...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/13/2002 |
| _version_ | 1797480580292542464 |
|---|---|
| author | Keerthana Chithanathan Kelli Somelar Monika Jürgenson Tamara Žarkovskaja Kapilraj Periyasamy Ling Yan Nathaniel Magilnick Mark P. Boldin Ana Rebane Li Tian Alexander Zharkovsky |
| author_facet | Keerthana Chithanathan Kelli Somelar Monika Jürgenson Tamara Žarkovskaja Kapilraj Periyasamy Ling Yan Nathaniel Magilnick Mark P. Boldin Ana Rebane Li Tian Alexander Zharkovsky |
| author_sort | Keerthana Chithanathan |
| collection | DOAJ |
| description | 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 (<i>Mir146b</i>-/-) mice exhibited anxiety-like behaviors and enhanced cognition. Characterization of cellular composition of <i>Mir146b</i>-/- 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 <i>Mir146b</i>-/- 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 <i>Mir146b</i>-/- mice. Further analysis demonstrated that miR-146b deficiency is associated with elevated expression of glial cell line-derived neurotrophic factor (<i>Gdnf</i>) 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 <i>Gdnf</i> mRNA expression in <i>Mir146b</i>-/- 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. |
| first_indexed | 2024-03-09T22:02:06Z |
| format | Article |
| id | doaj.art-f0b902e15dbd449e92e550f49f74d86f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T22:02:06Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f0b902e15dbd449e92e550f49f74d86f2023-11-23T19:47:54ZengMDPI AGCells2073-44092022-06-011113200210.3390/cells11132002Enhanced Cognition and Neurogenesis in miR-146b Deficient MiceKeerthana Chithanathan0Kelli Somelar1Monika Jürgenson2Tamara Žarkovskaja3Kapilraj Periyasamy4Ling Yan5Nathaniel Magilnick6Mark P. Boldin7Ana Rebane8Li Tian9Alexander Zharkovsky10Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, EstoniaDepartment of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, EstoniaDepartment of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, EstoniaDepartment of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, EstoniaDepartment of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, EstoniaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, EstoniaDepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, EstoniaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, EstoniaDepartment of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, EstoniaThe 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 (<i>Mir146b</i>-/-) mice exhibited anxiety-like behaviors and enhanced cognition. Characterization of cellular composition of <i>Mir146b</i>-/- 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 <i>Mir146b</i>-/- 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 <i>Mir146b</i>-/- mice. Further analysis demonstrated that miR-146b deficiency is associated with elevated expression of glial cell line-derived neurotrophic factor (<i>Gdnf</i>) 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 <i>Gdnf</i> mRNA expression in <i>Mir146b</i>-/- 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.https://www.mdpi.com/2073-4409/11/13/2002miR-146bcognitionanxietyastrocytesmicroglianeurogenesis |
| spellingShingle | Keerthana Chithanathan Kelli Somelar Monika Jürgenson Tamara Žarkovskaja Kapilraj Periyasamy Ling Yan Nathaniel Magilnick Mark P. Boldin Ana Rebane Li Tian Alexander Zharkovsky Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice Cells miR-146b cognition anxiety astrocytes microglia neurogenesis |
| title | Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice |
| title_full | Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice |
| title_fullStr | Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice |
| title_full_unstemmed | Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice |
| title_short | Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice |
| title_sort | enhanced cognition and neurogenesis in mir 146b deficient mice |
| topic | miR-146b cognition anxiety astrocytes microglia neurogenesis |
| url | https://www.mdpi.com/2073-4409/11/13/2002 |
| work_keys_str_mv | AT keerthanachithanathan enhancedcognitionandneurogenesisinmir146bdeficientmice AT kellisomelar enhancedcognitionandneurogenesisinmir146bdeficientmice AT monikajurgenson enhancedcognitionandneurogenesisinmir146bdeficientmice AT tamarazarkovskaja enhancedcognitionandneurogenesisinmir146bdeficientmice AT kapilrajperiyasamy enhancedcognitionandneurogenesisinmir146bdeficientmice AT lingyan enhancedcognitionandneurogenesisinmir146bdeficientmice AT nathanielmagilnick enhancedcognitionandneurogenesisinmir146bdeficientmice AT markpboldin enhancedcognitionandneurogenesisinmir146bdeficientmice AT anarebane enhancedcognitionandneurogenesisinmir146bdeficientmice AT litian enhancedcognitionandneurogenesisinmir146bdeficientmice AT alexanderzharkovsky enhancedcognitionandneurogenesisinmir146bdeficientmice |