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This research was supported by the Sao Paulo Research Foundation - FAPESP [grant numbers 17/21155-3, 19/02787-4, 19/05957-8, 19/165742, 19/00849-2, and 2021/13622-6], the National Institutes for Science and Technology (INCT) - "Translational Medicine", FAPESP [grant numbers 14/50891-1], National Council for Scientific and Technological Development (CNPq) [grant numbers 2022-2952, 305883/2014-3 and 465458/2014-9], Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) - Finance Code 001, and Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior - PROEX-CAPES. NGC holds a CNPq 1A Research Fellowship.

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Audiogenic Seizures in the Streptozotocin-Induced Rat Alzheimer's Disease Model

Publicat a:Journal Of Alzheimers Disease. 94 (3): 1179-1196 - 2023-01-01 94(3), DOI: 10.3233/JAD-230153

Autors: Alves, Suelen Santos; Antonio Cortes de Oliveira, Jose; Lazarini-Lopes, Willian; Servilha-Menezes, Gabriel; Grigorio-de-Sant'Ana, Mariana; Del Vecchio, Flavio; Focosi Mazzei, Rodrigo; Sousa Almeida, Sebastiao; Milton Patricio da Silva Junior, Rui; Garcia-Cairasco, Norberto

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Background: Alzheimer's disease (AD) is a neurodegenerative and progressive disorder with no cure and constant failures in clinical trials. The main AD hallmarks are amyloid-beta (A beta) plaques, neurofibrillary tangles, and neurodegeneration. However, many other events have been implicated in AD pathogenesis. Epilepsy is a common comorbidity of AD and there is important evidence indicating a bidirectional link between these two disorders. Some studies suggest that disturbed insulin signaling might play an important role in this connection. Objective: To understand the effects of neuronal insulin resistance in the AD-epilepsy link. Methods: We submitted the streptozotocin (STZ) induced rat AD Model (icv-STZ AD) to an acute acoustic stimulus (AS), a known trigger of seizures. We also assessed animals' performance in the memory test, the Morris water maze and the neuronal activity (c-Fos protein) induced by a single audiogenic seizure in regions that express high levels of insulin receptors. Results: We identified significant memory impairment and seizures in 71.43% of all icv-STZ/AS rats, in contrast to 22.22% of the vehicle group. After seizures, icv-STZ/AS rats presented higher number of c-Fos immunopositive cells in hippocampal, cortical, and hypothalamic regions. Conclusion: STZ may facilitate seizure generation and propagation by impairment of neuronal function, especially in regions that express high levels of insulin receptors. The data presented here indicate that the icv-STZ AD model might have implications not only for AD, but also for epilepsy. Finally, impaired insulin signaling might be one of the mechanisms by which AD presents a bidirectional connection to epilepsy.

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