title: Microglial phospholipase D4 deficiency influences myelination during brain development.
abstract: Phospholipase D4 (PLD4) is expressed in activated microglia that transiently appear in white matter during postnatal brain development. Previous knockdown experiments using cultured microglia showed PLD4 involvement in phagocytosis and proliferation. To elucidate the role of PLD4 in vivo, PLD4-deficient mice were generated and the cerebella were examined at postnatal day 5 (P5) and P7, when PLD4 expression is highest in microglia. Wild type microglia showed strong immunoreactivity for microglial marker CD68 at P5, whereas CD68 signals were weak in PLD4-deficient microglia, suggesting that loss of PLD4 affects microglial activation. At P5 and P7, immunostaining for anti-myelin basic protein (MBP) antibody indicated a mild but significant delay in myelination in PLD4-deficient cerebellum. Similar change was also observed in the corpus callosum at P7. However, this difference was not apparent at P10, suggesting that microglial PLD4-deficiency primarily influences the early myelination stage. Thus, microglia may have a transient role in myelination via a PLD4-related mechanism during development.
authors.affiliation: Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Otani
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Hayashi
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.forename: Maya
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Baba
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000196:embryology*; D002531:Cerebellum / Q000166:cytology; D003337:Corpus Callosum / Q000378:metabolism; D005092:Exonucleases; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000201:enzymology*; D009186:Myelin Sheath / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005092:Exonucleases; D008562:Membrane Glycoproteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C557622:PLD4 protein, mouse