| Texto completo | |
| Autor(es): |
Vicente, Mariane C.
;
Stabile, Angelita M.
;
Amorim, Mateus
;
Anibal Silva, Conceicao E.
;
Patrone, Luis Gustavo A.
;
Cunha, Thiago M.
;
Bicego, Kenia C.
;
Almeida, Maria C.
;
Carrettiero, Daniel C.
;
Gargaglioni, Luciane H.
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF ALZHEIMER'S DISEASE; v. 95, n. 1, p. 21-pg., 2023-01-01. |
| Resumo | |
Background: Neuroinflammation in Alzheimer's disease (AD) can occur due to excessive activation of microglia in response to the accumulation of amyloid-beta peptide (A beta). Previously, we demonstrated an increased expression of this peptide in the locus coeruleus (LC) in a sporadic model for AD (streptozotocin, STZ; 2 mg/kg, ICV). We hypothesized that the STZ-AD model exhibits neuroinflammation, and treatment with an inhibitor of microglia (minocycline) can reverse the cognitive, respiratory, sleep, and molecular disorders of this model. Objective: To evaluate the effect of minocycline treatment in STZ model disorders. Methods: We treated control and STZ-treated rats for five days with minocycline (30 mg/kg, IP) and evaluated cognitive performance, chemoreflex response to hypercapnia and hypoxia, and total sleep time. Additionally, quantification of A beta, microglia analyses, and relative expression of cytokines in the LC were performed. Results: Minocycline treatment improved learning and memory, which was concomitant with a decrease in microglial cell density and re-establishment of morphological changes induced by STZ in the LC region. Minocycline did not reverse the STZ-induced increase in CO2 sensitivity during wakefulness. However, it restored the daytime sleep-wake cycle in STZ-treated animals to the same levels as those observed in control animals. In the LC, levels of A and expression of Il10, Il1b, and Mcp1 mRNA remained unaffected by minocycline, but we found a strong trend of minocycline effect on Tnf-alpha. Conclusion: Our findings suggest that minocycline effectively reduces microglial recruitment and the inflammatory morphological profile in the LC, while it recovers cognitive performance and restores the sleep-wake pattern impaired by STZ. (AU) | |
| Processo FAPESP: | 16/04412-0 - Alterações neuroanatômicas e funcionais do sistema respiratório no sono e na vigília em um modelo experimental para Doença de Alzheimer |
| Beneficiário: | Mariane Cristine Vicente |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 16/24577-3 - Alterações neuroanatômicas e funcionais do sistema respiratório no sono e na vigília em um modelo experimental para doença de Alzheimer |
| Beneficiário: | Luciane Helena Gargaglioni Batalhão |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |