Cellular approaches to central nervous system remyelination stimulation: thyroid hormone to promote myelin repair via endogenous stem and precursor cells

Abstract

Brain and spinal cord repair is a very difficult task in view of the extremely limited repair capability of the mature central nervous system (CNS). Thus, cellular therapies are regarded as a new frontier for both acute and chronic neurological diseases characterized by neuron or oligodendroglia degeneration. Although cell replacement has been considered as the primary goal of such approaches, in recent years greater attention has been devoted to the possibility that new undifferentiated cells in damaged nervous tissue might also act in autocrine-paracrine fashion, regulating the microenvironment through the release of growth factor and cytokines, also regulating immune response and local inflammation. In this review, repair of demyelinating disease using endogenous cells will be discussed in view of the critical role played by thyroid hormones (THs) during developmental myelination, focusing on the following points: 1) endogenous stem and precursor cells during demyelinating diseases; 2) TH homeostasis in the CNS; 3) cellular and molecular mechanism regulated by TH during developmental myelination and 4) a working hypothesis to develop a rationale for the use of THs to improve remyelination through endogenous stem and precursor cells in the course of demyelinating diseases.

Thyroid Hormone Signaling and Adult Neurogenesis in Mammals

“…These results suggest that although some neurogenesis can still occur in aged mice, it might not be sufficient to compensate for neurodegeneration. TH facilitate repair after neurodegenerative lesions (67, 68). It is plausible that their decline is linked to decreased repair in neurodegenerative diseases of aging.…”

White Matter Dementia: Origin, Development, Progress, and Prospects

“…Thyroid hormones are known to be important in myelination during development, and these hormones may prove useful in adults with myelin disorders. 47 An interesting molecule found in the brain that may help repair white matter after many types of injury is neuregulin, which appears to induce N-methyl-D-aspartate receptor-dependent myelination by oligodendrocytes. 48 Stimulation of oligodendrocytes to enhance myelination with the neurotrophins nerve growth factor and brainderived neurotrophic factor has also been proposed, 48,49 and oligodendrocyte stimulation after ischemia has been observed with the use of many diverse agents such as aspirin, cerebrolysin, thymosin b4, and sildenafil.…”

Thyroid hormones: Possible roles in epilepsy pathology

“…Though the repair capabilities of the spinal cord and brain are limited, THs exert regenerative effects on nerves cells. The myelination process was also shown to be dependent on THs function in both peripheral and central nervous systems [4]. THs are able to induce oligodendrocytes formation from multipotent neural stem cells and also play a role in regulating different developmental stages of oligodendrocytes [36,37].…”

“…The importance of THs in the central nervous system (CNS) function is well confirmed in both neonatal and adult hypothyroidism [reviewed in [3]]. In addition, THs promotes CNS repair, as it has been demonstrated that CNS re-myelination is dependent on these hormones [4]. In addition, THs have non-genomic and genomic effects on mitochondrial biogenesis and function [5] and decreased activity of THs in humans is linked to impaired mitochondrial biogenesis and function [6].…”