Expression of secretin in the rat prenatal and postnatal cerebellum

Abstract

The brain-gut peptide secretin has been used to treat subjects suffering from the neurodevelopmental disorder autism despite the controversy on its therapeutic efficacy. Recent evidence indicated that secretin and its receptors are expressed particularly prominently in the cerebellum, an area consistently reported to be affected in autism. This raises the interesting hypothesis that secretin may play a role in the normal development of the cerebellum and perhaps the etiology of autism. As a first step to prove this hypothesis we examined the expression of secretin peptide in the prenatal and neonatal rat cerebella. Standard immunohistochemical technique using antibodies against rat secretin was employed to study the expression of secretin in prenatal rat cerebella at E11, E14, E17, E20 and E22, as well as neonatal rat cerebella at P1, P4, P7, P11 and P14. Immunoreactive cells were visualized by 3,3-diaminobenzide tetrahydrochloride. Specificity of immunostainings was examined by performing controls either in the absence of primary antibody or liquid phase pre-absorption of secretin antiserum with secretin peptide. There were widespread immunopositive signals in neuronal somata in the cerebella at these developmental stages. As early as the prenatal stage at E17, secretin was found to be consistently expressed in the Purkinje cell layer. At prenatal stage E22 and all the neonatal stages being examined in this study, immunoreactivity for secretin was prominently detected in the medial deep nucleus of the developing cerebellum. These results suggest that secretin plays a role in the development of the cerebellum at neonatal and early postnatal stages. Furthermore, during these developmental stages, the Purkinje neuron is a source of secretin. Acknowledgement: Supported by the National Natural Science Foundation of China and the Research Grants Council of Hong Kong (N_CUHK 427/03).