Proteolipid Protein Regulates the Survival and Differentiation of Oligodendrocytes

Abstract

Proteolipid protein (PLP) has been postulated to play a critical role in the early differentiation of oligodendrocytes (OLs) in addition to its known role as a structural component of myelin.To identify this early function, we blocked the synthesis of PLP in glial cultures with antisense oligodeoxynucleotides that targeted the PLP initiation codon. Primary glial cultures were incubated with phosphorothioate-protected oligodeoxynucleotides (S-ODNs) for up to 11 d. PLP in OLs was reduced Ͼ90%. OLs treated with antisense S-ODNs appeared strikingly healthy as judged by (1) immunocytochemical staining for myelin glycolipids and myelin basic protein, (2) their prolonged survival compared with untreated cultures, and (3) their ability to reestablish membrane sheets after removal of the S-ODNs.Our studies show that PLP is required for elaboration and stability of the myelin membrane sheets made by most OLs, but it is not necessary for the network of processes established by OLs. More importantly, the number of OLs in the antisensetreated cultures was nearly sevenfold greater after a 10 -11 d incubation with S-ODNs than in control cultures. The number of proliferating OL progenitors was not increased in the antisensetreated cultures, indicating that the increase in the number of OLs was attributable to prolonged OL survival. The tissue culture studies reveal that the absence of PLP/DM20 has the positive effect of promoting OL survival but the negative effect of preventing their full differentiation. This finding clarifies many of the paradoxical findings seen in the PLP mutants, the PLP overexpressers, and the PLP Ϫ animals.

Kir4.1 Potassium Channel Subunit Is Crucial for Oligodendrocyte Development andIn VivoMyelination

“…Additionally at that stage, these cells elaborated large membrane sheaths that mimic the appearance of unfurled myelin sheaths ( Fig. 8C; Yang and Skoff, 1997). Mature oligodendrocytes formed ring structures around distal branches and partly myelinated closely located cells, indicating in vitro myelination.…”

Effect of Long‐Term Vigabatrin Administration on the Immature Rat Brain

“…In addition to the structural role, PLP might have some nonstructural role (39). It has been suggested that PLP might regulate differentiation and survival of oligodendrocytes (40 Several possible mechanisms could singly or multiply play a role in the VGB-induced delay in myelination and oligodendroglial cell death. First, it is possible that a nonspecific effect such as undernutrition could be involved because poor nutrition is known to disturb myelination (41), and decreased appetite and weight loss have been observed previously with VGB treatment (9,42).…”

Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres

“…[8][9][10][11][12][13][14][15], and 15 large neurospheres containing Ͼ400 cells (clones nos. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. The panel of individual cDNA libraries from 30 selected clones was generated and normalized.…”