THYROXINE TREATMENT AND THE RECOVERY OF PYRAMIDAL CELLS OF THE CEREBRAL-CORTEX FROM CHANGES INDUCED BY JUVENILE-ONSET HYPOTHYROIDISM

In contrast to the permanent alterations resulting from neonatal hypot hyroidism, the effects of juvenile-onset hypothyroidism on the number and distribution of spines along the apical shaft of pyramidal neurons of the visual cortex appeared to be potentially reversible with adequ ate thyroxine (T-4) 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 mu g T-4/100 g body weight per day had, however, only partially revers ed the changes induced by juvenile-onset hypothyroidism. We here study whether or not a higher dose of T-4 would totally reverse these effec ts. A group of rats were thyroid-ectomized at 40 days of age, and inje cted once daily with placebo or T-4 (1.75 mu g/100 g BW per day) from 70 to 90 days of age, a group on 1.50 mu g being included to compare w ith previous results. Spine number and distribution-were measured, as well as the concentrations of T-4 and triiodothyronine (T-3) in plasma , liver and brain. The activities of two hepatic enzymes were measured as thyroid hormone-sensitive biological end points. The 1.75-mu g dos e restored spine number to 88% of normal values and was markedly more effective than the 1.50-mu g dose, which increased it to 68%. The degr ee of restoration appeared related to the concentration of T-3,. It is concluded that the changes caused by juvenile-onset hypothyroidism in the number and distribution of dendritic spines along the apical shaf ts of pyramidal neurons are reversible, although complete restoration might require a higher dose of T-4, a continuous mode of administratio n, or longer period of treatment. (C) 1994 John Wiley and Sons, Inc.