Thyroxine treatment and the recovery of pyramidal cells of the cerebral cortex from changes induced by juvenile‐onset hypothyroidism

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Abstract
In contrast to the permanent alterations resulting from neonatal hypothyroidism, the effects of juvenile‐onset hypothyroidism on the number and distribution of spines along the apical shaft by pyramidal neurons of the visual cortex appeared to be potentially reversible with adequate thyroxine (T4) therapy (Ruiz‐Marcos et al., 1980, Brain Res. 185:91–102 and 1982, Brain Res. 239:559–574). Treatment with 0.20 or 1.50 μg T4/100 g body weight per day had, however, only partially reversed the changes induced by juvenile‐onset hypothyroidism. We here study whether or not a higher dose of T4 would totally reverse these effects. A group of rats were thryoid‐ectomized at 40 days of age, and injected once daily with placebo or T4 (1.75 μg/100 g BW per day) from 70 to 90 days of age, a group on 1.50 μg being included to compare with previous results. Spine number and distribution‐were measured, as well as the concentrations of T4 and triidothyronine (T3) in plasma, liver and brain. The activities of two hepatic enzymes were measured as thyroid hormone‐sensitive biological end points. The 1.75‐μg dose restored spine number to 88% of normal values and was markedly more effective than the 1.50‐μg dose, which increased it to 68%. The degree of restoration appeared related to the concentration of T3. It is concluded that the changes caused by juvenile‐onset hypothyroidism in the number and distribution of dendritic spines along the apical shafts of pyramidal neurons are reversible, although complete restoration might require a higher dose of T4, a continuous mode of administration, or longer period of treatment. 1994 John Wiley & Sons, Inc.

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