DCX+ neuronal progenitors contribute to new oligodendrocytes during remyelination in the hippocampus

Scientific Reports, 2020 · DOI: 10.1038/s41598-020-77115-w · Published: November 20, 2020

Regenerative Medicine Neurology Genetics

Simple Explanation

The study investigates the ability of hippocampal DCX+ NPCs to generate oligodendrocytes under conditions requiring myelin repair. The research uses cuprizone to induce demyelination and remyelination in the hippocampus of transgenic mice. The findings suggest that DCX-expressing NPCs can contribute to the generation of mature oligodendrocytes during remyelination in the hippocampus.

Study Duration

8 weeks

Participants

Wildtype 2-month-old male C57BL/6J mice and transgenic DCX-CreERT2/Flox-EGFP mice

Evidence Level

Not specified

Key Findings

1
During remyelination, the number of GFP+ NPCs co-expressing Olig2 and CC1 significantly increased in the hippocampal DG.
2
A higher portion of newly generated BrdU-labeled cells were GFP+ NPCs during remyelination.
3
There was an increase in new oligodendrocytes derived from proliferating GFP+ NPCs during remyelination.

Research Summary

The study aimed to investigate if DCX+ NPCs can replace lost oligodendrocytes in the hippocampal DG after cuprizone-induced demyelination. The results showed a significant cuprizone-induced depletion of oligodendroglial cells and demyelination, followed by spontaneous recovery upon cuprizone withdrawal. Fate mapping analysis revealed a small number of GFP+Olig2+CC1+ cells in healthy controls, suggesting a small percentage of mature oligodendrocytes in the hippocampal DG are derived from DCX-expressing NPCs.

Practical Implications

Cell Lineage Plasticity

The potential for cell lineage plasticity is present in a subpopulation of hippocampal NPCs, suggesting they can differentiate into oligodendrocytes.

Therapeutic Potential

Understanding the role of DCX+ NPCs in remyelination may offer new therapeutic strategies for demyelinating diseases like multiple sclerosis.

Hippocampal Function

NPC-derived mature oligodendrocytes may play a role in spatial learning and memory consolidation within hippocampal-cortical networks.

Study Limitations

1
Whether oligodendrocytes derived from DCX-expressing NPCs actively contribute to axonal myelin sheaths still needs to be determined.
2
The analysis methods and cuprizone models used may explain some contradictory findings regarding the effect of cuprizone treatment on hippocampal neurogenesis.
3
Differential effects of cuprizone intoxication on NPC-derived and other oligodendroglial cells may have manifested at an earlier time point in the CC.

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