Thyroid hormone dependency of the developing dorsal raphe nucleus but not the superior cervical ganglion. Evidence from intraocular grafting experiments

Abstract

Immature superior cervical ganglia and brain stem pieces containing 5-hydroxytryptamine neurons of the dorsal raphe nucleus were grafted to the anterior eye chamber of intact and thyroidectomized recipients. The grafts were left in the eye to mature for 4-6 weeks and were measured through the translucent cornea repeatedly to follow survival and growth. Monoaminergic nerve fibre outgrowth from the grafts onto the host irides was evaluated with Falck-Hillarp monoamine histochemistry on iris whole mounts. Body weight and plasma concentrations of thyroid-stimulating hormone monitored the thyroid state of both experimental and control animals. Intraocular survival and growth of immature superior cervical ganglia was not influenced by thyroid hormone deficiency, whereas the size of dorsal raphe nucleus grafts significantly increased during similar conditions. This increased size was entirely counteracted by daily substitution with l-thyroxine (100 μg/kg, s.c.) to the thyroid deficient host animals. Fluorescence microscopy, including semiquantitative estimations of fibre outgrowth area and axon bundle formation in the irides, revealed no effects of the thyroid hormone deficiency on the peripheral superior cervical ganglia. The outgrowth of 5-hydroxytryptamine-containing nerve fibres from the brain stem grafts, on the other hand, showed a 50% decrease in both axon bundle formation and fibre outgrowth area in thyroidectomized hosts. This effect of the thyroidectomy could be completely reversed by daily substitution with l-thyroxine. These data strongly support earlier reports describing a thyroid hormone dependency for central noradrenaline- and dopamine-containing neurons during similar conditions. Furthermore, the results indicate a role of thyroid hormones for nerve fibre growth during development of intraocularly isolated central but not peripheral monoaminergic neurons.

Aberrant Monoaminergic System in Thyroid Hormone Receptor-β Deficient Mice as a Model of Attention-Deficit/Hyperactivity Disorder

“…The CPu has the highest expression of both TRα and TRβ in rats throughout the prenatal and neonatal periods but shows less expression of TRβ by adulthood ( Bradley et al, 1989 , 1992 ). In addition, thyroid hormone dependency of neurite outgrowth for 5-HT and noradrenaline- and DA-containing neurons has been reported in an ex vivo study ( Granholm et al, 1984 ). Therefore, TR mutant mice might develop neural disorganization due to a distinct growth inhibition in the basal ganglia, although detailed information on the synaptic functions has yet to be determined.…”

Control of the development of the ipsilateral retinothalamic projection in Xenopus laevis by thyroxine: Results and speculation

“…In a few studies, however, the development of isolated regions of the nervous system has been studied with regard to specific effects of thyroxine. In uiuo organ culture has been used to show that normal growth and bundling of processes from explants of some regions of the nervous system (locus coeruleus, substantia nigra, and brainstem), is thyroxine dependent, whereas for other regions (e.g., superior cervical ganglion), processes grow equally well in normal thyroxine-supplemented and in hypothyroid rats Granholm and Seiger, 1981;Granholm et al, 1984). In a separate study, the number of synapses in the molecular layer of the cerebellum was found to be decreased in hypothyroid rats (Nicholson and Altman, 1972b).…”