Tau in Oligodendrocytes Takes Neurons in Sickness and in Health

Abstract

Oligodendrocytes (OLGs), the myelin-forming cells of the central nervous system (CNS), are lifelong partners of neurons. They adjust to the functional demands of neurons over the course of a lifetime to meet the functional needs of a healthy CNS. When this functional interplay breaks down, CNS degeneration follows. OLG processes are essential features for OLGs being able to connect with the neurons. As many as fifty cellular processes from a single OLG reach and wrap an equal number of axonal segments. The cellular processes extend to meet and wrap axonal segments with myelin. Further, transport regulation, which is critical for myelination, takes place within the cellular processes. Because the microtubule-associated protein tau plays a crucial role in cellular process extension and myelination, alterations of tau in OLGs have deleterious effects, resulting in neuronal malfunction and CNS degeneration. Here, we review current concepts on the lifelong role of OLGs and myelin for brain health and plasticity. We present key studies of tau in OLGs and select important studies of tau in neurons. The extensive work on tau in neurons has considerably advanced our understanding of how tau promotes either health or disease. Because OLGs are crucial to neuronal health at any age, an understanding of the functions and regulation of tau in OLGs could uncover new therapeutics for selective CNS neurodegenerative diseases.

Focal cerebral ischemia induces changes in oligodendrocytic tau isoforms in the damaged area

“…In contrast, 4R‐Tau shows higher affinity and more efficiency at promoting microtubule assembly. 3R‐Tau is abundant in the neonatal brain and in immature oligodendrocytes cultured in vitro, whereas 4R‐Tau is profuse in the adult brain and mature oligodendrocyte cultures (Gorath et al, 2001; LoPresti, 2018). Our in vivo results, using immunofluorescence with isoform‐specific antibodies, indicate that 3R‐Tau and 4R‐Tau are present in the brains of healthy adult rats and that they have a similar distribution in interfascicular oligodendrocytes (mature) of the corpus callosum, mainly in the soma around the nucleus, a similar pattern of distribution to that found in mouse brain oligodendrocytes using antitotal tau antibodies (Kubo et al, 2019).…”

Developmental expression of human tau in Drosophila melanogaster glial cells induces motor deficits and disrupts maintenance of PNS axonal integrity, without affecting synapse formation

“…While Schwann cell-specific tau transgenic mice have not been generated, co-expression of tau in neuronal and glial cells, including Schwann cells, has been shown to result in neurodegeneration and Schwann cell death[15]. Tau is similarly toxic to myelinating cells in the CNS as oligodendrocyte-specific tau expression disrupts the maintenance of myelin integrity[7], consistent with in vitro experiments overexpressing tau in cultured oligodendrocytes[16]. Considering these observed consequences of tau expression in glial cells, as well as the critical contribution of glia in the development of the nervous system[17], we set out to determine whether glial tau expression disrupts the development and/or early maintenance of the PNS.…”

HDAC6 in Diseases of Cognition and of Neurons

“…HDAC6 also regulates acetylated Tau in OLGs. Tau participates in many aspects of OLG biology, including myelin formation, myelin integrity, and myelin repair [ 68 , 69 , 70 ]. The relationship between HDACi and inflammation is a complex one.…”