Perinatal, not adult, hypothyroidism suppresses dopaminergic axon sprouting in the deafferented olfactory tubercle of adult rat

Abstract

We reported recently that chronic thyroid deficiency in rat, beginning in utero and terminating after maturity, suppresses lesion-induced central catecholaminergic axon sprouting in the adult brain [Gottesfeld et al, 1985]. The present work was undertaken to define the critical period of hypothyroidism on subsequent neuronal sprouting. Thyroid hormones deficiency was induced in rats by methimazole during (a) gestational days 8-21 (20 mg/kg/day in the drinking water); (b) postnatal days 1-15 (0.2 or 0.4 mg/pup/day; i.p.), or (c) in the mature animal for 4 weeks (20 mg/kg/day in the drinking water). The olfactory tubercles (OTs) were used as a model to study sprouting of dopaminergic (DA) nerve terminals, elicited by olfactory bulbectomy. Animals in each group received lesions or sham operations as adults, and sacrificed 3 weeks after the operation. Thus, for each of the above treatments four subgroups were formed: (a) euthyroid/sham-operation, (b) euthyroid/lesion, (c) hypothyroid/sham-operation, and (d) hypothyroid/lesion. Sprouting of DA axon terminals in the OTs was identified by biochemical assays and quantitative immunofluorescent microscopy, using tyrosine hydroxylase (TH) as a marker. Serum thyroxine levels served as an index of the thyroid status. The results demonstrate that lesion-induced sprouting of DA axon terminals in OTs of adult rats is suppressed by hypothyroidism induced prenatally or during the early postnatal period, but not after maturity. Thus, there is a perinatal critical period during which altered thyroid function exerts long-term effects on neuronal plasticity.

The Effects of Thyroid Hormone on Insulin-Like Growth Factor (IGF) and IGF-Binding Protein (IGFBP) Expression in the Neonatal Rat: Prolonged High Expression of IGFBP-2 in Methimazole- Induced Congenital Hypothyroidism*

“…IGFBP-2 probe also hybridizes with an additinal larger-size 3.8 kb transscript of unknown origin, which mirrors the intensities of the 1.4 kb IGFBP-2 mRNAs. (15,18). Similarly, several maturational processes of the gastrointestinal tract are also thyroid dependent (19,20).…”

Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) but Not Insulin-Like Growth Factor-I (IGF-I) Remains Elevated in Euthyroid TSH-Suppressed Graves' Disease

“…The significance of these observations is unclear. However, studies in animals have shown that the effect of thyroid hormone on growth and development was age-dependent; expression of IGF-l and its binding proteins in congenital or neonatal hypothyroid rats can only be normalised when T4 replacement was started during the first week of life (21), and that there is a critical perinatal period in these animals where intact thyroid function is essential for normal maturation of central nervous system (22,23).…”

Seasonal plasticity of A15 dopaminergic neurons in the ewe

“…It was found in adult rats that when some of these neurons are lesioned, the remaining A10 neurons sprout collaterals, and it is speculated that this is a result of removal of a non-dopaminergic input (Gilad and Reis 1979). This effect was examined in perinatal rats that were hypothyroid, and this sprouting is suppressed in animals that are hypothyroid prenatally or in the early postnatal period (Gottesfeld Garcia, and Chronister 1987). However, animals that are hypothyroid after maturity do not experience suppression in lesion-induced collateral sprouting.…”