Developmental changes of tau protein and mRNA in cultured rat brain oligodendrocytes

Abstract

Oligodendrocytes elaborate an extensive network of multibranched processes and flat membranous sheets. Microtubules (MT) participate in the elaboration and stabilization of myelin-forming processes and are essential for cellular sorting processes. Microtubule-associated proteins (MAPs) are involved in the regulation and stabilization of the dynamic MT network. It has been shown previously that oligodendrocytes express the MAP tau, a phosphoprotein most abundant in neurons of the CNS. In this article, we demonstrate for the first time that oligodendrocytes contain all six tau isoforms, and that tau mRNA and protein expression is developmentally regulated. Immunoblot analysis reveals that tau protein is more abundant, and mature isoforms are more prominent at later stages of development. During the first week of culture maturation, a marked decrease in phosphorylation is observable. Using an RT-PCR approach, we can show that oligodendrocytes express small amounts of exon 3 containing isoforms and that during culture maturation, tau mRNA splice products with 3 MT-binding domains (3R) decrease and mRNA with 4 MT-binding domains (4R) increase. In situ hybridization study demonstrates that tau mRNA is present in precursor cells and in mature oligodendrocytes. Tau mRNA is actively transported into the cellular processes, is specifically present in the primary and some of the secondary processes, enriched at the turning and branching points and the growing tips, and often appears as small patches. Hence, localized tau translation at specific sites in the cellular extensions might contribute to the regulation of MT stability during process formation, early axonal contact establishment, and myelination.

Protein aggregate formation in oligodendrocytes: tau and the cytoskeleton at the intersection of neuroprotection and neurodegeneration

“…It has been implied that in adult rodent brain only 4R-tau isoforms are expressed. However, our data demonstrated that in rat brain 3R-tau isoforms are present yet at a much lower level (Müller et al, 1997;Gorath et al, 2001), which was later corroborated by Hanes et al (2009). In cultured oligodendrocytes tau protein is developmentally regulated and 4R-isoforms become more prominent, while 3R-isoforms decrease (Seiberlich et al, 2015).…”

“…In cultured oligodendrocytes derived from the brains of newborn rats all six tau isoforms are present and during in vitro differentiation tau heterogeneity increases while a decrease in phosphorylation is observed (Gorath et al, 2001). It has been implied that in adult rodent brain only 4R-tau isoforms are expressed.…”

“…In cultured oligodendrocytes tau protein is developmentally regulated and 4R-isoforms become more prominent, while 3R-isoforms decrease (Seiberlich et al, 2015). Tau mRNA is actively transported to the cellular processes Brought to you by | MIT Libraries Authenticated Download Date | 5/12/18 1:47 PM and particularly present in the primary processes (Gorath et al, 2001). Oligodendroglial tau is phosphorylated at multiple sites identified by antibodies against AT-8, PHF-1 and 12E8.…”

Trans-regulation of oligodendrocyte myelination by neurons through small GTPase Arf6-regulated secretion of fibroblast growth factor-2

“…4), similar to the NSC-Arf6-CKO mice. As it has been reported that tau is expressed in oligodendrocyte lineage cells 11 , we examined whether Cre recombination occurs in oligodendrocytes of the Tau-Cre mice using LacZ reporter mice, but did not observe any such events ( Supplementary Fig. 5).…”

Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

“…In normal neurons, tau associates with microtubules and promotes microtubule stability by suppressing dynamic instability. Tau protein has been implicated in numerous cellular processes, including neurite outgrowth [4,5,19], microtubule transport [11], and oligodendrocyte maturation [13,18]. When hyperphosphorylated, as in AD, tau protein self-aggregates to form NFTs.…”