Perinatal, not adult, hypothyroidism suppresses dopaminergic axon sprouting in the deafferented olfactory tubercle of adult rat.
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.
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
D008713:Methimazole; D014446:Tyrosine 3-Monooxygenase; D013974:Thyroxine; D004298:Dopamine