MEX3C induces cognitive impairment in mice through autophagy inhibition
Abstract Background The muscle excess 3 (MEX3C) protein comprises one of two conserved KH hnRNP K homology domains of the Caenorhabditis elegans protein family, a gene involved in the metabolism of key RNAs at posttranscriptional levels during the development of C. elegans, but its function in mamma...
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.3245 |
| _version_ | 1797632526764736512 |
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| author | Kai Wang Hao‐Nan Zhang Yong Du |
| author_facet | Kai Wang Hao‐Nan Zhang Yong Du |
| author_sort | Kai Wang |
| collection | DOAJ |
| description | Abstract Background The muscle excess 3 (MEX3C) protein comprises one of two conserved KH hnRNP K homology domains of the Caenorhabditis elegans protein family, a gene involved in the metabolism of key RNAs at posttranscriptional levels during the development of C. elegans, but its function in mammals is unclear. Methods and results In this study, we found that MEX3C plays a key role in learning and cognitive function. The learning and cognitive abilities of MEX3C‐knockout (KO) mice were significantly decreased relative to those of wild‐type (WT) mice in behavioral experiments, including the shuttle box, Morris water maze, and new object recognition. Nissl staining showed a decrease in the number of Nissl bodies and in the maturation of hippocampal and cortical neurons. A Western blot analysis of the neuron‐specific nuclear (NeuN) protein NEUN protein showed that the expression of that protein was decreased, which was consistent with the results of Nissl staining. Of note, the expression of sequestosome I p62 and Parkin BCL‐2‐associated X (Bax) Bax and B‐cell lymphoma‐2 (Bcl‐2) Bcl‐2 proteins also showed a downward trend, suggesting that the MEX3C gene may cause a decrease in the number and maturity of neuronal cells by increasing apoptosis through the inhibition of autophagy. In addition, Golgi staining showed that the complexity of neurons in the hippocampus and cerebral cortex was reduced, and the postsynaptic density protein 95 and growth‐associated protein (GAP‐43) also showed different degrees of reduction. Conclusion The KO of the MEX3C gene reduces the plasticity of synapses in various regions of the hippocampus, thereby affecting the function of the hippocampus and eventually causing the decline of cognitive function. On the other hand, compared with WT mice, MEX3C‐KO mice showed increased anxiety‐like behaviors in minefield and elevated plus maze tests. |
| first_indexed | 2024-03-11T11:39:16Z |
| format | Article |
| id | doaj.art-1a289006724b4998875167e06125efa5 |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-03-11T11:39:16Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-1a289006724b4998875167e06125efa52023-11-10T06:53:59ZengWileyBrain and Behavior2162-32792023-11-011311n/an/a10.1002/brb3.3245MEX3C induces cognitive impairment in mice through autophagy inhibitionKai Wang0Hao‐Nan Zhang1Yong Du2School of Clinical Medicine Ningxia Medical University Ningxia Yinchuan ChinaSchool of Clinical Medicine Ningxia Medical University Ningxia Yinchuan ChinaDepartment of Pediatric Surgery General Hospital of Ningxia Medical University Ningxia Yinchuan ChinaAbstract Background The muscle excess 3 (MEX3C) protein comprises one of two conserved KH hnRNP K homology domains of the Caenorhabditis elegans protein family, a gene involved in the metabolism of key RNAs at posttranscriptional levels during the development of C. elegans, but its function in mammals is unclear. Methods and results In this study, we found that MEX3C plays a key role in learning and cognitive function. The learning and cognitive abilities of MEX3C‐knockout (KO) mice were significantly decreased relative to those of wild‐type (WT) mice in behavioral experiments, including the shuttle box, Morris water maze, and new object recognition. Nissl staining showed a decrease in the number of Nissl bodies and in the maturation of hippocampal and cortical neurons. A Western blot analysis of the neuron‐specific nuclear (NeuN) protein NEUN protein showed that the expression of that protein was decreased, which was consistent with the results of Nissl staining. Of note, the expression of sequestosome I p62 and Parkin BCL‐2‐associated X (Bax) Bax and B‐cell lymphoma‐2 (Bcl‐2) Bcl‐2 proteins also showed a downward trend, suggesting that the MEX3C gene may cause a decrease in the number and maturity of neuronal cells by increasing apoptosis through the inhibition of autophagy. In addition, Golgi staining showed that the complexity of neurons in the hippocampus and cerebral cortex was reduced, and the postsynaptic density protein 95 and growth‐associated protein (GAP‐43) also showed different degrees of reduction. Conclusion The KO of the MEX3C gene reduces the plasticity of synapses in various regions of the hippocampus, thereby affecting the function of the hippocampus and eventually causing the decline of cognitive function. On the other hand, compared with WT mice, MEX3C‐KO mice showed increased anxiety‐like behaviors in minefield and elevated plus maze tests.https://doi.org/10.1002/brb3.3245autophagycognitive impairmentMEX3C protein |
| spellingShingle | Kai Wang Hao‐Nan Zhang Yong Du MEX3C induces cognitive impairment in mice through autophagy inhibition Brain and Behavior autophagy cognitive impairment MEX3C protein |
| title | MEX3C induces cognitive impairment in mice through autophagy inhibition |
| title_full | MEX3C induces cognitive impairment in mice through autophagy inhibition |
| title_fullStr | MEX3C induces cognitive impairment in mice through autophagy inhibition |
| title_full_unstemmed | MEX3C induces cognitive impairment in mice through autophagy inhibition |
| title_short | MEX3C induces cognitive impairment in mice through autophagy inhibition |
| title_sort | mex3c induces cognitive impairment in mice through autophagy inhibition |
| topic | autophagy cognitive impairment MEX3C protein |
| url | https://doi.org/10.1002/brb3.3245 |
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