Cold exposure elevates thyrotropin-releasing hormone gene expression in medullary raphe nuclei: Relationship with vagally mediated gastric erosions

Abstract

The stimulation of thyrotropin release by cold is associated with an increase in thyrotropin-releasing hormone gene expression in the paraventricular nucleus of the hypothalamus. Cold exposure also stimulates autonomic outflow to viscera. There is evidence that caudal raphe nuclei are involved in autonomic regulation through thyrotropin-releasing hormone projections to the dorsal vagal complex and spinal cord. To determine whether cold modulates thyrotropin-releasing hormone gene expression in the caudal raphe nuclei, the effect of cold exposure on thyrotropin-releasing hormone messenger RNA levels in the rat lower brainstem was examined by quantitative Northern blot analysis and thyrotropin-releasing hormone messenger RNA was localized by in situ hybridization. The gastric responses to cold exposure were also assessed in sham or vagotomized rats with pylorus ligation. Thyrotropin-releasing hormone messenger RNA signal was detected in the RNA extracted from the medulla and hypothalamus but not from the amygdala, periaqueductal gray or cerebellum. Cold exposure (4°C) for 1 or 3 h increased thyrotropin-releasing hormone messenger RNA levels in the medulla by77 ± 37 and142 ± 39% respectively. In situ hybridization histochemistry showed that the increase in silver grain density occurred exclusively in the raphe pallidus and raphe obscurus. Exposure to cold stress for 2 h stimulated gastric acid secretion and resulted in gastric lesion formation in sham but not vagotomized rats. There are established thyrotropin-releasing hormone projections from the raphe pallidus and obscurus to the dorsal vagal complex. Thyrotropin-releasing hormone is known to exert an excitatory effect on neurons of the dorsal motor nucleus of the vagus, leading to vagally mediated stimulation of gastric function and erosions. The increased thyrotropin-releasing hormone gene expression in the raphe pallidus and obscurus induced by cold supports an important role of endogenous thyrotropin-releasing hormone contained in caudal raphe nuclei-dorsal vagal complex pathways in vagally mediated changes in gastric function induced by cold.