Triiodothyronine Exerts a Trophic Action on Rat Sensory Neuron Survival and Neurite Outgrowth through Different Pathways

Abstract

Apart from several growth factors which play a crucial role in the survival and development of the central and peripheral nervous systems, thyroid hormones can affect different processes involved in the differentiation and maturation of neurons. The present study was initiated to determine whether triiodothyronine (T3) affects the survival and neurite outgrowth of primary sensory neurons in vitro. Dorsal root ganglia (DRG) from 19-day-old embryos or newborn rats were plated in explant or dissociated cell cultures. The effect of T3 on neuron survival was tested, either in mixed DRG cell cultures, where neurons grow with non-neuronal cells, or in neuron-enriched cultures where non-neuronal cells were eliminated at the outset. T3, in physiological concentrations, promoted the growth of neurons in mixed DRG cell cultures as well as in neuron-enriched cultures without added nerve growth factor (NGF). Since neuron survival in neuron-enriched cultures cannot be promoted by endogenous neurotrophic factors synthesized by non-neuronal cells, the increased number of surviving neurons was due to a direct trophic action of T3. Another trophic effect was revealed in this study: T3 sustained the neurite outgrowth of sensory neurons in DRG explants. The stimulatory effect of T3 on nerve fibre outgrowth was considerably reduced when non-neuronal cell proliferation was inhibited by the antimitotic agent cytosine arabinoside, and was completely suppressed when the great majority of non-neuronal cells were eliminated in neuron-enriched cultures. These results indicate that the stimulatory effect of T3 on neurite outgrowth is mediated through non-neuronal cells. It is conceivable that T3 up-regulates Schwann cell expression of a neurotrophic factor, which in turn stimulates axon growth of sensory neurons. Together, these results demonstrate that T3 promotes both survival and neurite outgrowth of primary sensory neurons in DRG cell cultures. The trophic actions of T3 on neuron survival and neurite outgrowth operate under two different pathways.

Regulation of herpes simplex virus type 1 thymidine kinase gene expression by thyroid hormone receptor in cultured neuronal cells

“…The presence of TR in sensory neurons indicates that the feedback regulation of circulating TH could occur by binding to the receptors (Glauser & Barakat Walter, 1997). T 3 can affect different processes involved in the survival, differentiation, and maturation of neurons (Walter, 1996). In a physiological concentration, T 3 enhances neurite outgrowth of primary sensory neurons in cultures, possibly in combination with nerve growth factor, to regulate the expression of cytoplasmic dynein, a protein that is involved in retrograde axonal transport (Barakat-Walter & Riederer, 1996).…”

Lysine metabolism in mammalian brain: an update on the importance of recent discoveries

“…The discovery that CRYM is a P2C reductase, and its enzyme activity regulated by T 3 is consistent with the possibility that P2C and Pyr2C may also have neurotransmitter/neuromodulator roles. Thyroid hormones are known to affect neuronal differentiation and also to cause neurite outgrowth (Walter 1996). Further research is necessary to determine to what extent the inter-relationship between CRYM/KR, its cyclic ketimine substrates, as well as thyroid hormones, play in neuronal differentiation.…”

Regulation of Microglial Development: A Novel Role for Thyroid Hormone

“…Similar to other neural cells (Walter, 1996;Baas et al, 1997;Lima et al, 1997), purified ameboid microglial cells respond to T3 exposure by increased extension of cell processes, an important step in their acquisition of a ramified phenotype. As for the effect on cell survival, it may be hypothesized that increased or decreased levels of T3 reaching microglial cells contribute to augment or reduce microglial process formation in hyperthyroid and hypothyroid rats, respectively.…”