Sleep deprivation modulates APOE and LDL receptor-related protein 1 through thyroid hormone T4 and impairs Aβ clearance in hippocampus of rats

Autor(es)

Mello da Luz, Marcio Henrique ; Volejnik Pino, Jessica Monteiro ; Monico-Neto, Marcos ; de Amorim, Priscila Nicolicht ; Moreira Antunes, Hanna Karen ; Porcionatto, Marimelia Aparecida ; Lee, Kil Sun

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE; v. 1869, n. 6, p. 12-pg., 2023-08-01.

Resumo

Alzheimer's disease is the most common form of dementia. One of its pathological hallmarks is A beta accumulation, which is influenced by APOE genotype and expression, as well as by sleep homeostasis. However, conflicting mechanisms for APOE roles in A beta clearance have been reported, and the relationship between APOE and sleep also remains unclear. In this study, we aimed to investigate how hormonal alteration caused by sleep deprivation affects APOE and its receptors in rats, and to evaluate the role of different cell types in A ss clearance. Paradoxical sleep deprivation for 96 h increased A beta level in hippocampus with concomitant reduction of APOE and LRP1 at the time point within the resting period. Sleep deprivation also significantly reduced T4 levels in both active and resting times. To evaluate the effect of T4 variation, C6 glial cells and primary brain endothelial cells were treated with T4. High T4 level (300 ng/mL) increased APOE, but reduced LRP1 and LDL-R in C6 cells, while in primary endothelial cells, LDL-R levels were increased. Treatment of C6 cells with exogenous APOE reduced LRP1 and A beta uptake. These results suggest that T4 modulates LRP1 and LDL-R in both cell types, but in the opposite manner, thus, sleep deprivation might modify the ratio of the receptors in blood-brain barrier and glial cells by altering T4 levels. Considering that LRP1 and LDL-R are important for A beta clearance, sleep deprivation might also affect the degree of participation of glia in A beta clearance, and consequently, turnover of A beta in the brain. (AU)

• Processo FAPESP: 18/12605-8 - Desenvolvimento de microplataformas brain-on-a-chip para modelagem do sistema nervoso central in vitro
• Beneficiário: Marimélia Aparecida Porcionatto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/04297-6 - Impactos da nutrição e do sono no perfil de expressão, solubilidade e função das proteínas neurais.
• Beneficiário: Kil Sun Lee
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/10404-2 - Avaliação dos efeitos da privação de sono no metabolismo e função de peptídeos beta-amiloide
• Beneficiário: Márcio Henrique Mello da Luz
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/21511-0 - Estudo da relação entre a homeostase de ferro e o metabolismo de macronutrientes associada a patologia da obesidade
• Beneficiário: Kil Sun Lee
• Modalidade de apoio: Auxílio à Pesquisa - Regular