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Microglial phospholipase D4 deficiency influences myelination during brain development
Terumasa Chiba1, Yoshinori Otani, Yoshihide Yamaguchi
1Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences.
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.
Insights
Phospholipase D4 (PLD4) deficiency in microglia delays early brain myelination. This suggests a transient role for microglial PLD4 in supporting the development of white matter during early postnatal stages.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Phospholipase D4 (PLD4) is expressed in microglia during early brain development.
- Previous studies indicated PLD4's role in microglial phagocytosis and proliferation in vitro.
- The in vivo function of PLD4 in microglia remains largely uncharacterized.
Purpose of the Study:
- To investigate the in vivo role of Phospholipase D4 (PLD4) in microglial function during postnatal brain development.
- To determine the impact of PLD4 deficiency on microglial activation and myelination processes.
Main Methods:
- Generation of PLD4-deficient mice.
- Analysis of cerebella and corpus callosum at specific postnatal days (P5, P7, P10).
- Immunohistochemistry using microglial marker CD68 and myelin marker anti-myelin basic protein (MBP).
Main Results:
- PLD4-deficient microglia exhibited reduced CD68 immunoreactivity, indicating impaired activation.
- A mild but significant delay in myelination was observed in the cerebella and corpus callosum of PLD4-deficient mice at P5 and P7.
- The observed delay in myelination was transient, with no significant difference by P10.
Conclusions:
- Microglial PLD4 plays a role in microglial activation during early postnatal development.
- PLD4 deficiency in microglia transiently impairs the early stages of brain myelination.
- Microglia may utilize PLD4-dependent mechanisms to transiently support myelination during development.
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