Platelet-derived growth factor delays oligodendrocyte differentiation and axonal myelination in vivo in the anterior medullary velum of the developing rat

Abstract

The AA dimeric form of platelet-derived growth factor (PDGF-AA) is implicated in the differentiation of cells of the oligodendrocyte lineage, which express PDGF receptors of the alpha subunit type (PDGF-alphaR). In the present study, we show that a single injection of PDGF-AA into the cerebrospinal fluid of neonatal rats delays oligodendrocyte differentiation and interrupts the progress of myelination in the anterior medullary velum (AMV), a white matter tract roofing the IVth ventricle of the brain. PDGF-AA or saline was injected intrathecally in postnatal day (P) 7 rats, and the AMV was subsequently removed and immunolabelled with the oligodendrocyte-specific antibody Rip, at P9, P12, and P21, corresponding to postinjection days (PID) 2, 5, and 14. At P9 (PID2), myelination was retarded in PDGF-AA-treated rats as opposed to saline-treated controls but progressed rapidly after P12 (PID5). Quantification supported the qualitative observations that PDGF-AA mediated an acute decrease in the number of Rip+ oligodendrocytes at P9-12, which largely recovered by P21, suggesting that PDGF-AA may have delayed recruitment of myelinating oligodendrocytes. However, the definitive number of Rip+ oligodendrocytes in the AMV was not increased, suggesting that its action as a promoter of early oligodendrocyte survival may not ultimately affect the definitive number of myelinating oliogdendrocytes in vivo. We discuss the possibilities that excess PDGF-AA may have acted on early oligodendrocytes (precursors or preoligodendrocytes) to either (1) delay their differentiation by maintaining them in the cell cycle or (2) accelerate their differentiation, which may result in premature cell death in the absence of synchronised survival signals. This study supports a role for PDGF-AA in the timing of oligodendrocyte differentiation in vivo, as has been shown in vitro.

CSF and Brain Indices of Insulin Resistance, Oxidative Stress and Neuro-Inflammation in Early versus Late Alzheimer’s Disease

“…PDGF-AA, which was measured in the gut hormone panel, has an important role in myelin maintenance [93]. PDGF-A receptor is regulated by β-FGF [93], and PDGF regulates oligodendrocyte progenitor cells functions, including myelination [94,95]. Therefore, the reduced levels of PDGF in AD correspond with the previously demonstrated early loss of white matter and hypomyelination in this disease [96,97].…”

Chondroitinase and Growth Factors Enhance Activation and Oligodendrocyte Differentiation of Endogenous Neural Precursor Cells after Spinal Cord Injury

“…We combined ChABC with administration of EGF, bFGF and PDGF-AA to enhance the survival of transplanted NPCs and direct their fate into oligodendrocytes. PDGF-AA is growth factor secreted by astrocytes in the CNS that promotes the proliferation of neural progenitors and stimulates the differentiation of oligodendrocytes [44], [45], and is also implicated in the survival of and migration of newly formed oligodendrocytes [46], [47]. Moreover, PDGF, in synergy with bFGF, regulates the proliferative response of adult oligodendrocyte progenitors [48], [49], [50].…”

Mitogen‐activated protein kinase signalling in oligodendrocytes: a comparison of primary cultures and CG‐4

“…Looking at the two differentiation pathways in more detail, PDGF and bFGF can be seen to enhance immature OL proliferation and delay differentiation to mature OL in both cell types. For instance, studies on primary OL have shown that PDGF can delay OL differentiation when injected into the cerebrospinal fluid of neonatal rats (Butt et al, 1997). As well, decreases in PDGF signalling have been shown to correspond to an exit of proliferative, immature OL from the cell cycle, and anti-PDGF antibodies have been shown block OL mitosis (Dutly and Schwab, 1991;Calver et al, 1998).…”