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Disrupted function of lactate transporter MCT1 , but not MCT4 , in Schwann cells affects the maintenance of motor end‐plate innervation
Author(s) -
Bouçanova Filipa,
Pollmeier Gill,
Sandor Katalin,
Morado Urbina Carlos,
Nijssen Jik,
Médard JeanJacques,
Bartesaghi Luca,
Pellerin Luc,
Svensson Camilla I,
Hedlund Eva,
Chrast Roman
Publication year - 2021
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.23889
Subject(s) - biology , microbiology and biotechnology , motor neuron , axon , monocarboxylate transporter , crosstalk , schwann cell , conditional gene knockout , myelin , neuroglia , neuroscience , transporter , biochemistry , central nervous system , spinal cord , phenotype , gene , physics , optics
Recent studies in neuron‐glial metabolic coupling have shown that, in the CNS, astrocytes and oligodendrocytes support neurons with energy‐rich lactate/pyruvate via monocarboxylate transporters (MCTs). The presence of such transporters in the PNS, in both Schwann cells and neurons, has prompted us to question if a similar interaction may be present. Here we describe the generation and characterization of conditional knockout mouse models where MCT1 or MCT4 is specifically deleted in Schwann cells (named MCT1 and MCT4 cKO). We show that MCT1 cKO and MCT4 cKO mice develop normally and that myelin in the PNS is preserved. However, MCT1 expressed by Schwann cells is necessary for long‐term maintenance of motor end‐plate integrity as revealed by disrupted neuromuscular innervation in mutant mice, while MCT4 appears largely dispensable for the support of motor neurons. Concomitant to detected structural alterations, lumbar motor neurons from MCT1 cKO mice show transcriptional changes affecting cytoskeletal components, transcriptional regulators, and mitochondria related transcripts, among others. Together, our data indicate that MCT1 plays a role in Schwann cell‐mediated maintenance of motor end‐plate innervation thus providing further insight into the emerging picture of the biology of the axon‐glia metabolic crosstalk.