title: 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.
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000097:blood / Q000502:physiology*; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007037:Hypothyroidism / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008713:Methimazole; D009416:Nerve Regeneration; D009830:Olfactory Bulb / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000097:blood; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D008713:Methimazole; D014446:Tyrosine 3-Monooxygenase; D013974:Thyroxine; D004298:Dopamine