Transient upregulation of procaspase-3 during oligodendrocyte fate decisions.

Oligodendrocytes are generated throughout life and in neurodegenerative conditions from brain resident oligodendrocyte precursor cells (OPCs). The transition from OPC to oligodendrocyte involves a complex cascade of molecular and morphological states that position the cell to make a fate decision to integrate as a myelinating oligodendrocyte or die through apoptosis. Oligodendrocyte maturation impacts the cell death mechanisms that occur in degenerative conditions, but it is unclear if and how the cell death machinery changes as OPCs transition into oligodendrocytes.

Oligodendrocyte Maturation Alters the Cell Death Mechanisms That Cause Demyelination.

Myelinating oligodendrocytes die in human disease and early in aging. Despite this, the mechanisms that underly oligodendrocyte death are not resolved and it is also not clear whether these mechanisms change as oligodendrocyte lineage cells are undergoing differentiation and maturation. Here, we used a combination of intravital imaging, single-cell ablation, and cuprizone-mediated demyelination, in both female and male mice, to discover that oligodendrocyte maturation dictates the dynamics and mechanisms of cell death.

Oligodendrocyte death initiates synchronous remyelination to restore cortical myelin patterns in mice.

Myelin degeneration occurs in neurodegenerative diseases and aging. In these conditions, resident oligodendrocyte progenitor cells (OPCs) differentiate into oligodendrocytes that carry out myelin repair. To investigate the cellular dynamics underlying these events, we developed a noninflammatory demyelination model that combines intravital two-photon imaging with a single-cell ablation technique called two-photon apoptotic targeted ablation (2Phatal).

Myelin plasticity in adulthood and aging.

The central nervous system maintains the potential for molecular and cellular plasticity throughout life. This flexibility underlies fundamental features of neural circuitry including the brain's ability to sense, store, and properly adapt to everchanging external stimuli on time scales from seconds to years. Evidence for most forms of plasticity are centered around changes in neuronal structure and synaptic strength, however recent data suggests that myelinating oligodendrocytes exhibit certain forms of plasticity in the adult.

A Synthetic Microbial Operational Amplifier.

Synthetic biology has created oscillators, latches, logic gates, logarithmically linear circuits, and load drivers that have electronic analogs in living cells. The ubiquitous operational amplifier, which allows circuits to operate robustly and precisely has not been built with biomolecular parts. As in electronics, a biological operational-amplifier could greatly improve the predictability of circuits despite noise and variability, a problem that all cellular circuits face.