Excitotoxic lesion by hypoxia-ischemia alters expression and distribution of AP-2 coat proteins and expression of NMDA-R in certain areas of rat brain

TRONCOSO,ME; FORMICA SAIG, PJ; SOSA MA; SELTZER, AM

Huerta Grande. Córdoba. Argentina

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2013

Sociedad Argentina de Investigaciones en Neurociencias

Introduction: AP-2 is a protein adaptor complex involved in the clathrin-mediated endocytosis, that interacts with motifs of the cytoplasmic domain of glutamate receptors, as a step in formation of clathrin coated vesicles. These receptors are known to be important players in the excitotoxic lesions and in neurodegenerative diseases. Aims: As the NMDA receptors (NMDA-R) are recognized by AP-2, and assuming that membrane-bound AP-2 is an index of endocytic activity, we studied the expression and distribution of AP-2 in areas of rat brain subjected to excitotoxic lesion by hypoxia-ischemia, and attempted to correlate with expression of NMDAR. Methods: Seven days old rats (Wistar- Kyoto) received hypoxia-ischemia treatment by ligature of the left carotid artery followed by short exposure to 100% N2 .Brain tissues were obtained 72 h after lesion, and α-2 subunit of AP-2 was evaluated by WB in membranes and cytosols from hippocampus (HIP), striatum (ST) and motor cortex (MC). Expression of NMDA-R was also studied in the membranes of the areas under study. Results: We observed that AP-2 bound to membranes tends to increase in the MC and HIP but not in the ST. In turn, expression of the NMDA-R was also increased in the injured tissues (bilaterally). Conclusions: These results indicate that certain brain areas undergo modifications in the endocytic machinery due to excitotoxic lesion, altering possibly the distribution of NMDA-R and, consequently, the glutamatergic synapses. (Libro de Resumenes pp168)