SOMATOSTATIN RECEPTORS IN THE HUMAN CEREBELLUM DURING DEVELOPMENT

The ontogeny of somatostatin receptors (SRIF-R) was studied in the human cerebellum from mid-gestation to the 15th month postnatal. The brains were collected 3-26 h after death, from 18 fetuses and infants, and from 4 adults aged from 48 to 82. SRIF-R were characterized by membrane-binding assay and their localization was determined by in vitro autoradiography. Both techniques were conducted with two radio-ligands: [I-125-Tyr0,(D)Trp8]S14 and D-Phe-Cys-I-125-Tyr-(D)Trp-Lys-Thr-Cys-Thr-ol (I-125-SMS 204-090). Membrane-binding studies carried out with each radioligand showed the presence of a single population of saturable, high affinity binding sites. Neither were the K(d) values for either ligand (assessed by Scatchard analysis) changed appreciably during development, mean K(d) values being 0.36 +/- 0.04 nM and 0.56 +/-0.11 nM for [I-125-Tyr0,(D)Trp8]S14 and I-125-SMS 204-090, respectively. Although inter-individual fluctuations of the B(max) were observed, the concentration of SRIF-R in the cerebellum of fetuses and infants up to 8 months appeared to be at least 2- to 10-fold higher than in the adult cerebellum. No appreciable differences in the B(max) values were found using either radioligand. The highest density of SRIF-R was observed in the cerebellar cortex of fetuses, in particular in the external granule cell layer (EGC), where stem cells of the granule cells are generated and enter the differentiation process. A high density of SRIF-R also occurred in the internal granule cell layer. In the molecular layer (ML) moderate labelling was detected as long as the EGC was present (from 20 weeks antenatal to 8 months postnatal), and during migration of granule cells through the ML. These observations strongly suggest that, in the cerebellar cortex, SRIF-R are mainly expressed by granule cells. A moderate density of SRIF-R was observed in the medulla from 20 weeks of fetal life to the 8th month postnatal, a maturation stage which corresponds to the establishment of the 3-layer organization of the human cerebellar cortex. No autoradiographic labelling was observed in the deep nuclei of the cerebellum. These results show that SRIF-R, expressed in the cerebellar cortex of human fetuses long before the onset of synaptic transmission, are likely borne by neuroblasts of the EGC. The occurrence of high concentrations of SRIF-R during fetal life and the first months postnatal suggests that SRIF may exert neurotrophic activities during maturation of the cerebellum.