Abstract
Myelination greatly increases the speed of action potential propagation of neurons, thereby enhancing the efficacy of inter-neuronal communication and hence, potentially, optimizing the brain’s signal processing capability. The impact of genetic variation on the extent of axonal myelination and its consequences for brain functioning remain to be determined. Here we investigated this question using a genetic reference panel (GRP) of mouse BXD recombinant inbred (RI) strains, which partly model genetic diversity as observed in human populations, and which show substantial genetic differences in a variety of behaviors, including learning, memory and anxiety. We found coherent differences in the expression of myelin genes in brain tissue of RI strains of the BXD panel, with the largest differences in the hippocampus. The parental C57BL/6J (C57) and DBA/2J (DBA) strains were on opposite ends of the expression spectrum, with C57 showing higher myelin transcript expression compared with DBA. Our experiments showed accompanying differences between C57 and DBA in myelin protein composition, total myelin content, and white matter conduction velocity. Finally, the hippocampal myelin gene expression of the BXD strains correlated significantly with behavioral traits involving anxiety and/or activity. Taken together, our data indicate that genetic variation in myelin gene expression translates to differences observed in myelination, axonal conduction speed, and possibly in anxiety/activity related behaviors.
Highlights
Various transcripts were investigated that are known to be associated with different myelin compartments, e.g., compact myelin (myelin proteolipid protein (PLP), Myelin basic protein (MBP), MAL, Myelin-associated oligodendrocyte basic protein (MOBP)), non-compact myelin (MAG, myelin oligodendrocyte glycoprotein (MOG)), and radial component (Claudin11)
We set out to investigate whether genetic differences in myelin transcription are present in BXD lines, which may underlie brain molecular, functional and behavioral differences in these strains
These results are in line with the literature on myelin gene expression, indicating the presence of transcription factors that regulate expression of groups of oligodendrocyte and myelin genes [53,55,56,57,58]
Summary
The myelin membrane forces the axonal action potential to be generated only at interruptions of non-myelinated areas of the axon, called the nodes of Ranvier, resulting in a fast, saltatory movement of the action potential along the axon [1,2]. Formation of myelin around neuronal axons is a complex process, which in the central nervous system (CNS) involves oligodendrocytes that provide insulation by locally wrapping their cellular processes around axons. Oligodendrocytes and myelin provide metabolic support to axons, which is crucial for neuron survival and activity [2]. In accordance with myelin fundamentally changing the way neural impulses are generated and transmitted, loss of myelin integrity can lead to severe neurological symptoms [1,2]. With the findings that activity-dependent myelination may underlie an additional mechanism of nervous system
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