Somatostatin-14 induces different changes in the thymus of peripubertal and young adult rats

Abstract

Bearing in mind the role of somatostatin in thymus functions, and changes of somatostatin level and expression of its receptors during postnatal life, the aim of this study was to investigate whether centrally applied SRIH-14 induces different changes in the thymic compartments and thymocyte profile in peripubertal and young adult rats. To this end, 4- and 10-week-old male AO rats were cannulated and treated intracerebroventriculary with three doses of SRIH-14, applied every other day. In peripubertal rats, SRIH-14 decreases thymic relative weight and volume, as well as the volume of thymic compartments, especially of deep cortex, as a result of thymocytes loss by apoptosis. Also, SRIH-14 increases the percentage of immature thymocytes preceding the DPTCRαβlow cells (DNTCRαβ-/low, DPTCRαβ-, SPCD8TCRαβ-/low and SPCD4TCRαβ-/low), decreases the percentages of DPTCRαβlow and DPTCRαβhi cells, while the relative proportion of CD4+/CD8+TCRαβhi cells remained unaltered. In young adult rats, SRIH-14 does not lead to changes in relative thymus weight, although decreases the thymic cortex cellularity and volume. In addition, decreases the percentage of DPTCRαβ-/hi cells and increases the percentages of cells within DNTCRαβhi and both SP subpopulations, but much more of the CD8+TCRαβhi subset. These results suggest that the effects of SRIH-14 on the thymus and thymocytes subpopulations are age-dependent.

Sa obzirom da literaturni podaci ukazuju da somatostatin ima uticaja na funkciju timusa, kao i da se tokom postnatalnog života menja nivo somatostatina i ekspresija njegovih receptora u timusu, cilj ovog rada je bio da se ispita da li SRIH- 14 davan intracerebroventrikularno u prepubertalnih i mladih odraslih pacova, dovodi do različitih promena u zonama timusa i profilu timocitnih subsetova. Mužjacima pacova AO soja, starim 4 i 10 nedelja, ugrađene su kanile u treću moždanu komoru i oni su tretirani somatostatinom, ukupno tri doze, ubrizgane svakog drugog dana. U prepubertalnih pacova tretman somatostatinom dovodi do smanjenja relativne mase i zapremine timusa, kao i zapremine timusnih zona, naročito dubokog korteksa, što je bila posledica gubitka timocita apoptozom. Takođe, SRIH-14 je doveo do povećanja procenta timocita nezrelog fenotipa (DNTCRαβ-/low, DPTCRαβ-, SPCD8TCRαβ-/low i SPCD4TCRαβ-/low) prekusora DPTCRαβlow subpopulacije, smanjenja procenta DPTCRαβlow i DPTCRαβhi subsetova, dok je relativni odnos najzrelijih CD4TCRαβhi i CD8TCRαβhi timocita ostao neizmenjen. U mladih adulta primena somatostatina, iako dovodi do smanjena zapremine i celularosti korteksa ne dovodi do promena u relativnoj masi timusa. Procenat DPTCRαβ-/hi timocita je bio smanjen, dok je procentualno učešće DNTCRαβhi timocita i obe jednostruko pozitivne subpopulacije (CD4TCRαβhi i CD8TCRαβhi, više CD8TCRαβhi) u ukupnom broju timocita bilo povećano. Navedeni rezultati ukazuju da SRIH-14 različito utiče na morfologiju timusa i na subpopulacije timocita pacova u zavisnosti od uzrasta tretiranih životinja.