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Myelin basic protein mRNA levels affect myelin sheath dimensions, architecture, plasticity, and density of resident

Hooman Bagheri1, Hana Friedman1, Amanda Hadwen2

  • 1Department of Human Genetics, McGill University, Montreal, Quebec, Canada.

Glia
|July 18, 2024
PubMed

Insights

Altered Myelin Basic Protein (MBP) levels impact central nervous system (CNS) myelin thickness and structure throughout life. Reduced MBP mRNA levels surprisingly led to increased glial cell density, revealing new cellular interactions.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Genetics

Background:

  • Myelin Basic Protein (MBP) is crucial for central nervous system (CNS) myelin development and maintenance.
  • Reduced MBP accumulation leads to hypomyelination, but the effects of varying Mbp mRNA levels on myelin dimensions and glial responses across the lifespan remain unclear.

Purpose of the Study:

  • To investigate how different Mbp mRNA levels influence myelin dimensions throughout the lifespan.
  • To explore the response of resident glial cells to altered Mbp mRNA levels.

Main Methods:

  • Utilized enhancer-edited mouse lines with Mbp mRNA levels from 8% to 160% of wild type.
  • Assessed myelin sheath thickness, length, structure, MBP protein accumulation, and glial cell density across different age groups.

Main Results:

  • In young mice, lower Mbp mRNA levels correlated with reduced MBP protein and myelin thickness, confirming MBP's role in initial myelin synthesis.
  • Over time, myelin thickness and MBP levels improved or normalized even with sustained low mRNA levels, with normalization rate dependent on mRNA abundance.
  • Myelin sheath length was affected only at very low mRNA levels, indicating differential regulation compared to thickness.
  • Reduced mRNA levels led to structural abnormalities and an unexpected increase in the density of all glial cell types.

Conclusions:

  • MBP levels and transcription play a critical role in myelin sheath elaboration, architecture, and plasticity across the lifespan.
  • Altered MBP levels induce significant changes in myelin structure and glial cell populations.
  • A novel crosstalk between glial cells in response to altered MBP expression was identified.
Keywords:
Mbp transcriptionastrocytehypermyelinationhypomyelinationmicrogliamyelin basic proteinmyelin elaboration and plasticitymyelin sheath thickness and lengtholigodendrocyte and oligodendrocyte progenitor cell

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