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

• DOI: 10.1038/tp.2017.80
• Publication Date: 2017-05-09T13:42:17Z
• Authors: D Mattei; A Ivanov; C Ferrai; P Jordan; D Guneykaya; A Buonfiglioli; W Schaafsma; P Przanowski; W Deuther-Conrad; P Brust; S Hesse; M Patt; O Sabri; T L Ross; B J L Eggen; E W G M Boddeke; B Kaminska; D Beule; A Pombo; H Kettenmann; S A Wolf
• Keywords: IN-VIVO PET; 18 KDA; Minocycline; NEGATIVE SYMPTOMS; Synaptic Transmission; HIPPOCAMPAL NEUROGENESIS; DOUBLE-BLIND; Immune System Phenomena; Mice; 03 medical and health sciences; Phagocytosis; DEFICITS; Alzheimer Disease; Pregnancy; ANIMAL-MODEL; Animals; Humans; 0303 health sciences; Behavior, Animal; HUMAN BRAIN; Anti-Bacterial Agents; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; EARLY-PHASE SCHIZOPHRENIA; Cardiovascular and Metabolic Diseases; Schizophrenia; Adult Children; Original Article; Female; Microglia; Technology Platforms; TRANSLOCATOR PROTEIN; Function and Dysfunction of the Nervous System; Transcriptome

AbstractMaternal 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.