| Full text | |
| Author(s): |
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
Total Authors: 10
|
| Document type: | Journal article |
| Source: | JOURNAL OF ALZHEIMER'S DISEASE; v. 94, n. 3, p. 18-pg., 2023-01-01. |
| Abstract | |
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. (AU) | |
| FAPESP's process: | 21/13622-6 - Assessing anxiety and painful hypersensitivity as comorbidities associated with Epilepsy: effects of cannabidiol treatment and the role of CB1, TRPV1 and 5-HT1A receptors |
| Grantee: | Willian Lazarini Lopes |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 14/50891-1 - INCT 2014: Translational Medicine |
| Grantee: | Jaime Eduardo Cecilio Hallak |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/21155-3 - Wistar audiogenic rat (WAR): a possible model for the study of Alzheimer's Disease related to insulin resistance |
| Grantee: | Suélen Santos Alves |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 19/02787-4 - Effects of cannabidiol vehiculated in nanoemulsion in rats submitted to the chemical model of temporal lobe epilepsy |
| Grantee: | Gabriel Servilha Menezes |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 19/00849-2 - Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS) |
| Grantee: | Rui Milton Patrício da Silva Junior |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 19/05957-8 - Epilepsies and neuropsyquiatric comorbidities: characterization of the effects of the treatment with cannabidiol and HUF-101 in in vivo and in vitro experimental models |
| Grantee: | Norberto Garcia Cairasco |
| Support Opportunities: | Regular Research Grants |