Neuronal expression of the proteolipid protein gene in the medulla of the mouse

Abstract

The proteolipid protein (PLP) gene (Plp) encodes the major myelin proteins, PLP and DM20. Expression of Plp occurs predominantly in oligodendrocytes, but evidence is accumulating that this gene is also expressed in neurons. In earlier studies, we demonstrated that myelin-deficient (MD) rats, which carry a mutation in the Plp gene, exhibit lethal hypoxic ventilatory depression. Furthermore, we found that, in the MD rat, PLP accumulated in neuronal cell bodies in the medulla oblongata. In the current study, we sought to determine which neurons expressed the Plp gene in the medulla oblongata and whether Plp gene expression changed in neurons with maturation. A transgenic mouse expressing the Plp promoter driving expression of enhanced green fluorescent protein (Plp-EGFP) was used to identify neurons expressing this gene. Plp expression in neurons was confirmed by immunostaining EGFP-positive cells for NeuN and by in situ hybridization for PLP mRNA. The numbers of neurons expressing Plp-EGFP and their distribution increased between P5 and P10 in the medulla. Immunostaining for surface receptors and classes of neurons expressing Plp-EGFP revealed that Plp gene expression in brainstem neurons was restricted to neurons expressing specific ligand-gated channels and biosynthetic enzymes, including glutamatergic NMDA receptors, GABA(A) receptors, and ChAT in defined areas of the medulla. Plp gene expression was rarely found in interneurons expressing GABA and was never found in AMPA receptor- or tyrosine hydroxylase-expressing neurons. Thus, Plp expression in the mouse caudal medulla was found to be developmentally regulated and restricted to specific groups of neurons.

Ecotropic Murine Leukemia Virus Infection of Glial Progenitors Interferes with Oligodendrocyte Differentiation: Implications for Neurovirulence

“…2E, arrows). The EGFP low cells in PLP-EGFP mice likely represent brainstem neurons, as previously described for these mice (55). We next examined the relationship of Olig2 expression to EGFP expression and cellular vacuolation.…”

“…In addition, certain brainstem neurons express much lower levels of EGFP (EGFPlow), allowing the two EGFP populations to be distinguished from one another (Fig. 2E to G) (55). Moreover, this differential expression facilitated a coincident morphological assessment of OLs and vulnerable neurons.…”

The Expression of TAG-1 in Glial Cells Is Sufficient for the Formation of the Juxtaparanodal Complex and the Phenotypic Rescue of Tag-1 Homozygous Mutants in the CNS

“…Previous studies have shown that the plp gene promoter is also active in some neuronal cells (Bongarzone et al, 1999;Miller et al, 2009;Gó mez-Casati et al, 2010). To investigate the possibility that transgenic TAG-1 protein may also be expressed in neurons, we performed a series of immunofluorescence experiments in vivo and in vitro.…”

M6 proteins regulate axon outgrowth in mouse callosal neurons

“…M6b interacts with the serotonin transporter and promote its expression on the cell surface (Fjorback et al, 2009) shown that PLP/DM20 is predominately expressed in oligodendrocytes. Although resent studies revealed that a splicing isoform of PLP/DM20 (sr-PLP/sr-DM20) is expressed in the mouse cortical neuron from E13 to P7 (Jacobs et al, 2003;Miller et al, 2009), anti-sr-PLP/DM20 antibody did not label axon tracts. The authors discussed that localization of this neuronal isoform is subcellularly restricted to the cell body of neurons.…”

“…Although PLP/DM20 has been believed as the main component of the myelin and solely expressed by oligodendrocytes, a recent study reports neuronal expression of a splicing isoform of PLP/DM20 in neurons (Miller 2009). To evaluate the contribution of PLP/DM20 in formation of the CC bundle, we made M6a-/-M6b-/Y PLP-/Y triple knockout mice.…”