POTENTIAL ROLE OF ANGIOTENSIN II AT2 RECEPTORS IN PURKINJE CELLS MIGRATION.

SÁNCHEZ SI; ME ARCE; CIUFFO GM

Los Cocos, Cba.

Congreso; Reunion de la Soc. Arg. de Neurociencias; 2009

Soc. Arg. de Neurociencias

POTENTIAL ROLE OF ANGIOTENSIN II AT2 RECEPTORS IN PURKINJE CELLS MIGRATION. Sanchez SI., Arce ME., Seltzer AM., Ciuffo GM. IMIBIO-SL CONICET- Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis. Angiotensin II (Ang II), the active component of the renin–angiotensin system, binds and activates two major subtype of receptors, namely AT1 and AT2. In the fetus, AT2 receptors predominate in all tissues and decline shortly after birth, being restricted to a few organs including brain. Interpretation of the function of Ang II in cerebellum necessitates a thorough understanding about the localization of Ang II receptors. A clear complementary pattern of AT1 and AT2 binding labeled by [125I] Ang II was  observed on adjacent layers in young rats within the cerebellar cortex. By using specific markers of the Purkinje cells (PCs) (Zebrin II and calbindin), we demonstrated that Ang II AT2 receptors co-localized with the PCs as a monolayer, in correspondence with the well-defined layer observed by binding autoradiography at differential developmental stages (P8 to P60). Blockade of AT2 receptors with PD12319 during late pregnancy caused a lost of AT2 binding in the external granular layer (EGL) in P0 pups. A detailed histological analysis evidenced an enlarged EGL in the cerebellar cortex. It is well known that PCs migrate early during fetal stage (E14) toward the cerebellar cortex. Cote et al. 1999, showed a role of Ang II AT2 receptors in cerebellar neuron migration.  PCs regulate proliferation of the granulose cells (Carletti, 2008). The lack of receptor stimulation during prenatal period by pharmacological blockade altered developing cerebellum. The enlarged EGL in the cerebellar cortex and the lack of binding at the EGL, suggest a potential role of Ang II AT2 receptors during PCs migration.