Maternal immune activation results in complex microglial transcriptome signature in the adult offspring that is reversed by minocycline treatment

被引：168

作者：

Mattei, D. ^{[1
]}

Ivanov, A. ^{[2
,3
]}

Ferrai, C. ^{[4
]}

Jordan, P. ^{[1
]}

Guneykaya, D. ^{[1
]}

Buonfiglioli, A. ^{[1
,5
]}

Schaafsma, W. ^{[6
]}

Przanowski, P. ^{[7
]}

Deuther-Conrad, W. ^{[8
]}

Brust, P. ^{[8
]}

Hesse, S. ^{[9
,10
]}

Patt, M. ^{[9
]}

Sabri, O. ^{[9
]}

Ross, T. L. ^{[11
]}

Eggen, B. J. L. ^{[6
]}

Boddeke, E. W. G. M. ^{[6
]}

Kaminska, B. ^{[7
]}

Beule, D. ^{[2
,12
]}

Pombo, A. ^{[4
]}

Kettenmann, H. ^{[1
]}

Wolf, S. A. ^{[1
]}

机构：

[1] Helmholtz Assoc, Max Delbrueck Ctr Mol Med, Cellular Neuroci, Robert Rossle Str 10, D-13125 Berlin, Germany

[2] Berlin Inst Hlth, Core Unit Bioinformat, Berlin, Germany

[3] Charite, Berlin, Germany

[4] Helmholtz Assoc, Epigenet Regulat & Chromatin Architecture Grp, Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Berlin, Germany

[5] Charite, Inst Cell Biol & Neurobiol, Berlin, Germany

[6] Univ Groningen, Univ Med Ctr Groningen, Sect Med Physiol, Dept Neurosci, Groningen, Netherlands

[7] Nencki Inst Expt Biol, Lab Mol Neurobiol, Warsaw, Poland

[8] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, Dept Neuroradiopharmaceut, Res Site Leipzig, Leipzig, Germany

[9] Univ Leipzig, Dept Nucl Med, Leipzig, Germany

[10] Univ Leipzig, Integrated Treatment & Res Ctr IFB Adipos Dis, Leipzig, Germany

[11] Hannover Med Sch, Dept Nucl Med, Hannover, Germany

[12] Helmholtz Assoc, Max Delbrueck Ctr Mol Med, Berlin, Germany

来源：

TRANSLATIONAL PSYCHIATRY | 2017年 / 7卷

关键词：

ANIMAL-MODEL; DOUBLE-BLIND; HIPPOCAMPAL NEUROGENESIS; TRANSLOCATOR PROTEIN; NEGATIVE SYMPTOMS; HUMAN BRAIN; 18; KDA; SCHIZOPHRENIA; DEFICITS; EXPRESSION;

D O I：

10.1038/tp.2017.80

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of neuronal signaling in the central nervous system. The beneficial effects of the immunomodulatory treatment with minocycline on schizophrenic patients are consistent with this hypothesis. Using the MIA mouse model, we found an altered microglial transcriptome and phagocytic function in the adult offspring accompanied by behavioral abnormalities. The changes in microglial phagocytosis on a functional and transcriptional level were similar to those observed in a mouse model of Alzheimer's disease hinting to a related microglial phenotype in neurodegenerative and psychiatric disorders. Minocycline treatment of adult MIA offspring reverted completely the transcriptional, functional and behavioral deficits, highlighting the potential benefits of therapeutic targeting of microglia in psychiatric disorders.

引用

页码：e1120 / e1120

页数：13

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