Secretin Activates Visceral Brain Regions in the Rat Including Areas Abnormal in Autism

1. The aim of this study was to determine whether central networks are involved in the presumptive behavioral and autonomic regulatory actions of secretin, a gut hormone that has been reported to have ameliorative effects in autistic children.2. Central neural responses monitored by regional c-fos gene expression were examined in response to intracerebroventricular secretin injection in awake, freely-moving Sprague-Dawley rats. Tissue sections were incubated in an antibody to the c-fosgene product, Fos, and processed immunohistochemically.3. Qualitative differences in Fos immunoreactivity in stress adaptation and visceral representation areas of the brain were observed between secretin- and vehicle-infused age-matched pairs (n = 4 pairs). Secretin-activated regions include the area postrema, dorsal motor nucleus, medial region of the nucleus of the solitary tract and its relay station in the lateral tegmentum, locus ceruleus, ventral periaqueductal gray, periventricular thalamic nucleus, paraventricular hypothalamus magnocellularis, medial and central amygdala, lateral septal complex as well as ependymal and subependymal nuclei lining the third ventricle. Specific areas of the cerebral cortex were heavily labeled in secretin-treated rats, as compared to controls: the medial bank of the anterior prefrontal cortex, orbitofrontal cortex, the piriform cortex, and the anterior olfactory nucleus. Secretin attenuated Fos immunoreactivity in the dorsal periaqueductal gray, intralaminar thalamus, medial parvicellular compartment of the hypothalamus, supraoptic nucleus of the hypothalamus, lateral amygdala, motor cortex, and the somatosensory and association areas of the parietal cortex.4. Secretin alters the activity of structures involved in behavioral conditioning of stress adaptation and visceral reflex reactions. This study predicts a possible cellular mechanism, activation of third ventricular ependymal and subependymal cells, as well as central regulatory actions of secretin. The physiological effects of secretin on behavioral, endocrine, autonomic and sensory neuronal activation patterns, together, contribute to central c-fos activation. Secretin alters the activity of structures involved in behavioral conditioning of stress adaptation and visceral reflex reactions. This study predicts a possible cellular mechanism, activation of third ventricular ependymal and subependymal cells, and central regulatory actions of secretin. The physiological effects of secretin on behavioral, endocrine, autonomic and sensory neuronal activation patterns, together, contribute to central c-fos activation. These findings mandate further investigation of secretin as a brain/gut stress regulatory hormone.