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Hypothyroidism increases Fos immunoreactivity in cholinergic neurons of brain medullary dorsal vagal complex in rats

¹Center for Ulcer Research and Education (CURE): Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System; and ²Department of Medicine, Division of Digestive Diseases and Brain Research Institute, University of California, Los Angeles, California

Submitted 11 March 2005 ; accepted in final form 20 June 2005

Hypo- or hyperthyroidism is associated with autonomic disorders. We studied Fos expression in the medullary dorsal motor nucleus of the vagus (DMV), nucleus tractus solitarii (NTS), and area postrema (AP) in four groups of rats with different thyroid states induced by a combination of drinking water and daily intraperitoneal injection for 1–4 wk: 1) tap water and vehicle; 2) 0.1% propylthiouracil (PTU) and vehicle; 3) PTU and thyroxine (T₄; 2 µg/100 g); and 4) tap water and T₄ (10 µg/100 g). The numbers of Fos immunoreactive (IR) positive neurons in the DMV, NTS, and AP were low in euthyroid rats but significantly higher in the 4-wk duration in hypothyroid rats, which were prevented by simultaneous T₄ replacement. Hyperthyroidism had no effect on Fos expression in these areas. There were significant negative correlations between T₄ levels and the numbers of Fos-IR-positive neurons in the DMV (r = –0.6388, P < 0.008), NTS (r = –0.6741, P < 0.003), and AP (r = –0.5622, P < 0.004). Double staining showed that Fos immunoreactivity in the DMV of hypothyroid rats was mostly localized in choline acetyltransferase-containing neurons. Thyroid hormone receptors 1 and 2 were localized in the observed nuclei. These results indicate that thyroid hormone influences the DMV/NTS/AP neuronal activity, which may contribute to the vagal-related visceral disorders observed in hypothyroidism.

thyroid hormone; dorsal motor nucleus of the vagus; nucleus tractus solitarii; vagus nerve; area postrema