BLOCKAGE OF ANG II AT2 RECEPTORS MODIFIES CHARACTERISTIC PURKINJE CELLS MONOLAYERING IN DEVELOPING CEREBELLUM.

SOLER GARCÍA F; SÁNCHEZ S.; CIUFFO G; FUENTES L.

Congreso; XXXII Reunión Anual de la Sociedad de Biología de Cuyo; 2014

Sociedad de Biología de Cuyo

Angiotensin II (Ang II) exerts its physiological effects through binding to two receptor subtypes: AT1 and AT2 receptors. Ang II AT2 receptor expression is highly modulated during development. In the fetus, AT2 receptors predominate in all tissues and decline shortly after birth, being restricted to a few organs including cerebellum. In this organ, AT2 receptors are located only in the Purkinje cells membrane; these cells are the ones that orchestrate the process of postnatal cerebelarcorticogenesis. The aim of the present study was to analyze theeffect of antagonist of Ang II type 2 receptors on the developing cerebellum. Treatment was performed during the last week of pregnancy with vehicle (control) and PD 123319 (AT2 antagonist, 1.0 mg/kg/day). The offspring was analyzed at different ages: PN3, PN5 and PN8. Morphological studies by histological analysis and indirect Immunofluorescence usinganti-calbindinantibody were performing. The detailed analysis revealed alterations in cerebellar layering: increased thickness of the EGL arises from increased proliferation of granule cell precursors, impaired formation of the characteristic Purkinje cell monolayer and arrest in dendriticarborization. Consequently, the present study demonstrates changes in cerebellar layering and Purkinje cell development in animals born from mothers treated with PD123319. Although treatment lasted for one week before birth we observed important effects on cerebellum development in P8 animals indicating that the damage continued even when there was no longer exposure to the drugs. These observations confirm previous assumptions that Ang II AT2 receptor plays an important role in cerebellum development.