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

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-ß (Aß) 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.

A Genetic Model of Epilepsy with a Partial Alzheimer's Disease-Like Phenotype and Central Insulin Resistance.

Studies have suggested an important connection between epilepsy and Alzheimer's disease (AD), mostly due to the high number of patients diagnosed with AD who develop epileptic seizures later on. However, this link is not well understood. Previous studies from our group have identified memory impairment and metabolic abnormalities in the Wistar audiogenic rat (WAR) strain, a genetic model of epilepsy. Our goal was to investigate AD behavioral and molecular alterations, including brain insulin resistance, in naïve (seizure-free) animals of the WAR strain. We used the Morris water maze (MWM) test to evaluate spatial learning and memory performance and hippocampal tissue to verify possible molecular and immunohistochemical alterations. WARs presented worse performance in the MWM test (p < 0.0001), higher levels of hyperphosphorylated tau (S396) (p < 0.0001) and phosphorylated glycogen synthase kinase 3 (S21/9) (p < 0.05), and lower insulin receptor levels (p < 0.05). Conversely, WARs and Wistar controls present progressive increase in amyloid fibrils (p < 0.0001) and low levels of soluble amyloid-ß. Interestingly, the detected alterations were age-dependent, reaching larger differences in aged than in young adult animals. In summary, the present study provides evidence of a partial AD-like phenotype, including altered regulation of insulin signaling, in a genetic model of epilepsy. Together, these data contribute to the understanding of the connection between epilepsy and AD as comorbidities. Moreover, since both tau hyperphosphorylation and altered insulin signaling have already been reported in epilepsy and AD, these two events should be considered as important components in the interconnection between epilepsy and AD pathogenesis and, therefore, potential therapeutic targets in this field.

Cognitive Abilities, Debt, Roads and their Impact on Deaths in Traffic in Brazil / Habilidades Cognitivas, Endividamento, Rodovias e seus Impactos nos Óbitos no Trânsito

Abstract Deaths in traffic represent a global and multicausal problem. We verified, through a linear regression model, that cognitive abilities (CA) and population indebtedness (PI) predict, together, 56% of the variation of death rates in the traffic (DT) of the twenty-seven states of Brazil. CA's are related to a greater control of the attention and, possibly, to a greater compliance with norms for preventing traffic accidents, has a greater impact than PI on DT, since PI associates to only one deficit of people's attention resources. The decrease of PI and the improvement of CA can decrease DT.

Resumo Os óbitos no trânsito representam um problema global e multicausal. Verificamos, por meio de um modelo de regressão linear, que as habilidades cognitivas (HC) e o endividamento populacional (ENDP), predizem, juntos, 56% da variação das taxas de óbitos no trânsito (TOT) das 27 unidades federativas (UF) do Brasil. As HC, por estarem relacionadas a um maior controle da atenção e, possivelmente, a um maior cumprimento de normas de prevenção contra acidentes de trânsito, possuem um impacto maior que o ENDP sobre as TOT, já que o ENDP associa somente a um deficit dos recursos de atenção das pessoas. A diminuição do ENDP e a melhoria das HC podem reduzir as TOT.