Abstracts

Rationale: The glucose uptake is increased through Na+/glucose cotransporter 1 (SGLT1) in hippocampus under epileptic seizure (J. Neurochem 1997; 69; 84-94). We showed that SGLT1 inhibition by phlorizin, a specific SGLT inhibitor, increased neuronal death in hippocampal subfields. It is known that the T1R2/T1R3 sweet is expressed in hippocampus (Front Integr Neurosci. 2009; 19; 1-15). Besides, glucose activates this heterodimer through the adenylate cyclase-cAMP-PKA route and increases SGLT1 expression (Eur. J. Biochem, 2003; 270, 3377-3388). We evaluated the effect of glucose availability in the neurodegeneration process. Methods: Experimental procedures were approved by the Ethical Committee for Animal Research of UFAL (04/2016). Male Wistar rats (n=28 [240-340g]) were submitted to stereotaxic surgery for implantation of a cannula in the hilus of dentate gyrus of hippocampus. The animals VEH+PILO and GLU+PILO received microinjections of vehicle (VEH, saline 0.9%, 1L) or glucose (GLU, increases SGLT expression, 2mM), respectively, in hippocampus followed 30 minutes later by pilocarpine (PILO) (1.2mg/L). In addition, PILO+GLU received GLU (1mM or 2mM) after 5 minutes of PILO. Animals were perfused after 24 hours of SE and neurodegeneration was evaluated by histochemistry of Fluoro-Jade (FJ). FJ positive neurons (FJ+) were counted (ImageJ?"NIH) in dorsal, medial and ventral hippocampus. Results were expressed as meanSEM, compared by one-way ANOVA followed by post-hoc test Student-Newman-Keuls. Results: FJ+ neurons in CA3 region on ventral hippocampus (269±45) were higher (p < 0.05) compared with in dorsal hippocampus (56±7) and medial (79±18) only in GLU+PILO rats. Furthermore, total number of FJ+ in CA3 (405±44) and CA1 (457±35) of hippocampus were higher (p < 0.05) in GLU+PILO than VEH+PILO (CA3, 170±61, CA1, 221±52). However, PILO+GLU (2mM) animals had a decreased number (p < 0.05) of FJ+ in hilus of dentate gyrus (28±10), CA3 (116±65) and CA1 (61±32) compared to GLU+PILO (hilus, 173±15, CA3, 405±44 and CA1, 457±35). Similarly, in PILO+GLU 1mM the total number of FJ+ reduced in hilus (76±9), CA3 (191±24) and CA1 (173±46) regarding to the same region of GLU+PILO group. In addition, FJ+ total neurons decreased in the hilus of PILO+GLU 2mM (28±10) and was unchanged in PILO+GLU 1 mM (76±9) compared to VEH+PILO (141±45). Conclusions: Together, these preliminary data suggest that possibly the administration of intrahippocampal glucose protects brain in the earlier stage of epileptogenic processes. Funding: FAPEAL, CNPQ.