The Eph receptor A4 plays a role in demyelination and depression-related behavior
Proper myelination of axons is crucial for normal sensory, motor, and cognitive function. Abnormal myelination is seen in brain disorders such as major depressive disorder (MDD), but the molecular mechanisms connecting demyelination with the pathobiology remain largely unknown. We observed demyelina...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2022-05-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI152187 |
| _version_ | 1818236581851430912 |
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| author | Yuan Li Ping Su Yuxiang Chen Jing Nie Ti-Fei Yuan Albert H.C. Wong Fang Liu |
| author_facet | Yuan Li Ping Su Yuxiang Chen Jing Nie Ti-Fei Yuan Albert H.C. Wong Fang Liu |
| author_sort | Yuan Li |
| collection | DOAJ |
| description | Proper myelination of axons is crucial for normal sensory, motor, and cognitive function. Abnormal myelination is seen in brain disorders such as major depressive disorder (MDD), but the molecular mechanisms connecting demyelination with the pathobiology remain largely unknown. We observed demyelination and synaptic deficits in mice exposed to either chronic, unpredictable mild stress (CUMS) or LPS, 2 paradigms for inducing depression-like states. Pharmacological restoration of myelination normalized both synaptic deficits and depression-related behaviors. Furthermore, we found increased ephrin A4 receptor (EphA4) expression in the excitatory neurons of mice subjected to CUMS, and shRNA knockdown of EphA4 prevented demyelination and depression-like behaviors. These animal data are consistent with the decrease in myelin basic protein and the increase in EphA4 levels we observed in postmortem brain samples from patients with MDD. Our results provide insights into the etiology of depressive symptoms in some patients and suggest that inhibition of EphA4 or the promotion of myelination could be a promising strategy for treating depression. |
| first_indexed | 2024-12-12T12:12:09Z |
| format | Article |
| id | doaj.art-f9a212c4dc274514b5a9c5aceea9f1ec |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-12-12T12:12:09Z |
| publishDate | 2022-05-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-f9a212c4dc274514b5a9c5aceea9f1ec2022-12-22T00:24:51ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-05-011328The Eph receptor A4 plays a role in demyelination and depression-related behaviorYuan LiPing SuYuxiang ChenJing NieTi-Fei YuanAlbert H.C. WongFang LiuProper myelination of axons is crucial for normal sensory, motor, and cognitive function. Abnormal myelination is seen in brain disorders such as major depressive disorder (MDD), but the molecular mechanisms connecting demyelination with the pathobiology remain largely unknown. We observed demyelination and synaptic deficits in mice exposed to either chronic, unpredictable mild stress (CUMS) or LPS, 2 paradigms for inducing depression-like states. Pharmacological restoration of myelination normalized both synaptic deficits and depression-related behaviors. Furthermore, we found increased ephrin A4 receptor (EphA4) expression in the excitatory neurons of mice subjected to CUMS, and shRNA knockdown of EphA4 prevented demyelination and depression-like behaviors. These animal data are consistent with the decrease in myelin basic protein and the increase in EphA4 levels we observed in postmortem brain samples from patients with MDD. Our results provide insights into the etiology of depressive symptoms in some patients and suggest that inhibition of EphA4 or the promotion of myelination could be a promising strategy for treating depression.https://doi.org/10.1172/JCI152187Cell biologyNeuroscience |
| spellingShingle | Yuan Li Ping Su Yuxiang Chen Jing Nie Ti-Fei Yuan Albert H.C. Wong Fang Liu The Eph receptor A4 plays a role in demyelination and depression-related behavior The Journal of Clinical Investigation Cell biology Neuroscience |
| title | The Eph receptor A4 plays a role in demyelination and depression-related behavior |
| title_full | The Eph receptor A4 plays a role in demyelination and depression-related behavior |
| title_fullStr | The Eph receptor A4 plays a role in demyelination and depression-related behavior |
| title_full_unstemmed | The Eph receptor A4 plays a role in demyelination and depression-related behavior |
| title_short | The Eph receptor A4 plays a role in demyelination and depression-related behavior |
| title_sort | eph receptor a4 plays a role in demyelination and depression related behavior |
| topic | Cell biology Neuroscience |
| url | https://doi.org/10.1172/JCI152187 |
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