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Acetyl‐CoA production from pyruvate is not necessary for preservation of myelin
Author(s) -
DellaFlora Nunes Gustavo,
Mueller Lauren,
Silvestri Nicholas,
Patel Mulchand S.,
Wrabetz Lawrence,
Feltri M. Laura,
Poitelon Yannick
Publication year - 2017
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23184
Subject(s) - myelin , biology , oligodendrocyte , microbiology and biotechnology , sciatic nerve , neurodegeneration , neuroglia , pyruvate dehydrogenase complex , neuroscience , central nervous system , anatomy , medicine , biochemistry , enzyme , disease
Oligodendrocytes and Schwann cells not only form myelin in the central and peripheral nervous system, but also provide metabolic and trophic support to the axons they ensheathe. Acetyl‐CoA is potentially a key molecule in Schwann cells and oligodendrocytes because it is at the crossroads of cellular lipid biosynthesis and energy generation. The main route for acetyl‐CoA production is the oxidation of pyruvate by the pyruvate dehydrogenase complex (PDC). PDC deficiency in humans results in neurodegeneration and developmental impairments in both white and gray matter structures. To address the importance of PDC in myelinating glia, we deleted Pdha1 gene specifically in oligodendrocytes and Schwann cells. Surprisingly, sciatic and optic nerve morphology and the motor performance of Pdha1 f/Y; Cnp Cre/+ mice are undistinguishable from those of controls at 1 month of age. In addition, myelin is stably maintained for at least 10 months. However, Pdha1 f/Y; Cnp Cre/+ mice showed reduced fiber density and signs of axonal degeneration in both sciatic and optic nerves from 6 months of age. In contrast, 10 month‐old mice bearing a floxed Pdha1 gene with either P0‐Cre (expressed only by Schwann cells) or NG2‐Cre ER (expressed in oligodendrocyte precursor cells) do not show any sign of axonal pathology or alterations in myelin structure or thickness. This indicates that the axonopathy is specific to the Pdha1 f/Y; Cnp Cre/+ mice. Taken together, these results suggest that acetyl‐CoA derived from pyruvate is not necessary for myelin maintenance and, thus, myelin‐forming cells are not likely to contribute to the pathophysiology of PDC deficiency.