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Journal Article

Microglia ablation alleviates myelin-associated catatonic signs in mice

MPS-Authors
/persons/resource/persons206046

Janova,  Hana
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons214271

Arinrad,  Sahab
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons214273

Balmuth,  Evan
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182304

Mitjans,  Marina
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons198205

Pan,  Hong
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182163

Goebbels,  Sandra
Developmental neurobiology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182563

Begemann,  Martin
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182160

Gerwig,  Ulrike C.
Developmental neurobiology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182481

Werner,  Hauke B.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182138

Ehrenreich,  Hannelore
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182320

Nave,  Klaus-Armin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Citation

Janova, H., Arinrad, S., Balmuth, E., Mitjans, M., Hertel, J., Habes, M., et al. (2018). Microglia ablation alleviates myelin-associated catatonic signs in mice. The Journal of Clinical Investigation, 128(2), 734-745. doi:10.1172/JCI97032.


Cite as: https://hdl.handle.net/21.11116/0000-0000-2FE6-9
Abstract
The underlying cellular mechanisms of catatonia, an executive “psychomotor” syndrome that is observed across neuropsychiatric diseases, have remained obscure. In humans and mice, reduced expression of the structural myelin protein CNP is associated with catatonic signs in an age-dependent manner, pointing to the involvement of myelin-producing oligodendrocytes. Here, we showed that the underlying cause of catatonic signs is the low-grade inflammation of white matter tracts, which marks a final common pathway in Cnp-deficient and other mutant mice with minor myelin abnormalities. The inhibitor of CSF1 receptor kinase signaling PLX5622 depleted microglia and alleviated the catatonic symptoms of Cnp mutants. Thus, microglia and low-grade inflammation of myelinated tracts emerged as the trigger of a previously unexplained mental condition. We observed a very high (25%) prevalence of individuals with catatonic signs in a deeply phenotyped schizophrenia sample (n = 1095). Additionally, we found the loss-of-function allele of a myelin-specific gene (CNP rs2070106-AA) associated with catatonia in 2 independent schizophrenia cohorts and also associated with white matter hyperintensities in a general population sample. Since the catatonic syndrome is likely a surrogate marker for other executive function defects, we suggest that microglia-directed therapies may be considered in psychiatric disorders associated with myelin abnormalities.