Thyroid Hormone Causes Sexually Distinct Neurochemical and Morphological Alterations in Rat Septal‐Diagonal Band Neurons

Abstract: Sex differences were investigated in cholinergic neurons of the septal‐diagonal band region of adult rats subjected to neonatal treatment with 3,3′,5‐triiodo‐L‐thyronine (T₃). Neonatal hyperthyroidism resulted in a 44% increase in specific activity of choline acetyltransferase (ChAT; EC 2.3.1.6) in adult male rat septal‐diagonal band region, whereas no change in ChAT activity could be detected in either dorsal or ventral hippocampus. An increase in muscarinic cholinergic receptors, as measured by [³H]quinu‐clidinyl benzilate ([³H]QNB) binding, was discovered in both septum‐diagonal band and dorsal hippocampus of the T₃‐treated male rats. Immunohistochemistry in the septal‐diagonal band region indicated a more intense staining in the neonatally T₃‐treated adult male rats than in controls, with larger and more abundant ChAT‐positive and nerve growth factor receptor (NGF‐R)‐positive varicosities. ChAT immunocytochemistry showed a substantial decrease in cell body area in the medial septum and in the vertical limb of the diagonal band of T₃‐treated male rats, while cell density increased twofold. Female littermates subjected to the same treatment showed no changes in any of the biochemical or immunohistochemical cholinergic markers. Only in the medial septum was morphology significantly altered in the female T₃‐treated rats in that ChAT‐positive cell body area increased. These results indicate a marked sexual variation in the septal‐diagonal band region with respect to the sensitivity of postnatally developing cholinergic neurons to the actions of excess thyroid hormone.