Early microglial response, myelin deterioration and lethality in mice deficient for very long chain ceramide synthesis in oligodendrocytes.

The sphingolipids galactosylceramide (GalCer), sulfatide (ST) and sphingomyelin (SM) are essential for myelin stability and function. GalCer and ST are synthesized mostly from C22-C24 ceramides, generated by Ceramide Synthase 2 (CerS2). To clarify the requirement for C22-C24 sphingolipid synthesis in myelin biosynthesis and stability, we generated mice lacking CerS2 specifically in myelinating cells (CerS2 ).

Remodelling of myelinated axons and oligodendrocyte differentiation is stimulated by environmental enrichment in the young adult brain.

Oligodendrocyte production and myelination continues lifelong in the central nervous system (CNS), and all stages of this process can be adaptively regulated by neuronal activity. While artificial exogenous stimulation of neuronal circuits greatly enhances oligodendrocyte progenitor cell (OPC) production and increases myelination during development, the extent to which physiological stimuli replicates this is unclear, particularly in the adult CNS when the rate of new myelin addition slows. Here, we used environmental enrichment (EE) to physiologically stimulate neuronal activity for 6 weeks in 9-week-old C57BL/six male and female mice and found no increase in compact myelin in the corpus callosum or somatosensory cortex.

Activity-dependent central nervous system myelination throughout life.

Myelin, the multilayered membrane surrounding many axons in the nervous system, increases the speed by which electrical signals travel along axons and facilitates neuronal communication between distant regions of the nervous system. However, how neuronal signals influence the myelinating process in the CNS is still largely unclear. Recent studies have significantly advanced this understanding, identifying important roles for neuronal activity in controlling oligodendrocyte development and their capacity of producing myelin in both developing and mature CNS.

BDNF haploinsufficiency exerts a transient and regionally different influence upon oligodendroglial lineage cells during postnatal development.

Brain-Derived Neurotrophic Factor (BDNF) plays important roles in promoting myelination in the developing central nervous system (CNS), however the influence it exerts on oligodendrocyte development in vivo remains unclear. As BDNF knockout mice die in the perinatal period, we undertook a systematic developmental analysis of oligodendroglial lineage cells within multiple CNS regions of BDNF heterozygous (HET) mice. Our data identify that BDNF heterozygosity results in transient reductions in oligodendroglial lineage cell density and progression that are largely restricted to the optic nerve, whereas the corpus callosum, cerebral cortex, basal forebrain and spinal cord white matter tracts are unaffected.