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

Abstract

Oligodendrocytes play a significant role in the central nervous system, as these cells are responsible for myelinating axons and allowing for the efficient conduction of nerve impulses. Therefore, any understanding we can gain about the functional biology of oligodendrocytes will give us important insights into demyelinating diseases such as multiple sclerosis, where oligodendrocytes and myelin are damaged or destroyed. Currently, much attention has focussed on the role of a family of mitogen-activated protein kinases in OL. This kinase family includes the extracellular signal-regulated protein kinases (ERKs), the stress-activated c-Jun N-terminal kinase (JNK), and the 38 kDa high osmolarity glycerol response kinase (p38). The actions of mitogen-activated protein kinases in oligodendrocytes appear to range from proliferation and cell survival to differentiation and cell death. In the past, studies on oligodendrocytes have been hampered by the difficulties inherent in producing large enough quantities of these cells for experimentation. This problem arises in large part due to the post-mitotic nature of mature oligodendrocytes. Over the years, a cell line known as Central Glia-4 (CG-4) has become a popular oligodendrocyte model due to its potentially unlimited capacity for self-renewal. In this review, we will look at the suitability of the Central Glia-4 cell line as an oligodendrocyte model, specifically in respect to studies on mitogen-activated protein kinase signalling in oligodendrocytes.

JC Virus Agnoprotein Inhibits In Vitro Differentiation of Oligodendrocytes and Promotes Apoptosis

“…It has previously been shown that the inactivation of ERKs together with the activation of JNK and/or p38 may be critical for apoptosis, and an increase in ERK activity has been correlated to the increased survival of CG-4 cells differentiated into oligodendrocytic cells (29) and neuronal cell survival (82), whereas an increase of JNK or p38 activity may trigger apoptosis (82). Mitogen withdrawal that induces differentiation of CG-4 into multipolar oligodendrocytic cells, at an early (30-min) stage, is associated with a reduction of CREB and p44/42 MAPK (ERK1/2) phosphorylation (48,72). We observed an inhibition of ERK activity by agnoprotein at late stages (4 days) of differentiation.…”

Hyperforin promotes mitochondrial function and development of oligodendrocytes

“…progenitor cells (Stariha and Kim, 2001). When the CG-4 cell line was first established, it was cultured in the conditioned medium generated from the culture of neuroblastoma B104 cells.…”

“…CG-4 cells began to show morphological characteristics of mature oligodendrocytes within two days when maintained in the differentiation medium (Stariha and Kim, 2001).…”

“…Usually, CG-4 cells began to show morphological characteristics of mature oligodendrocytes within two days (Stariha and Kim, 2001); NS/PCs began to show different types of neural cell markers within four days when maintained in the differentiation medium.…”

“…These data suggest that CG-4 may have a lesser degree of differentiation than primary O-2A progenitors. In one study, they identified the roles of protein kinase C (PKC) pathway and extracellular signal-regulated kinase (ERK) pathway in the differentiation and maturation of oligodendrocytes and found differences with CG-4 and primary O-2A progenitors (Stariha and Kim, 2001). Other than these reported differences, the CG-4 cell line is a valuable model to study oligodendrocyte biology.…”