Autor(es)

da Luz, Marcio H. M. ; Pino, Jessica M. V. ; Santos, Tiago G. ; Antunes, Hanna K. M. ; Martins, Vilma R. ; De Souza, Altay A. L. ; Torquato, Ricardo J. S. ; Lee, Kil S.

• Tipo de documento: Artigo Científico
• Fonte: Journal of Neurochemistry; v. 153, n. 3, p. 13-pg., 2020-02-05.

Resumo

PrP (c) is a glycoprotein capable to interact with several molecules and mediates diverse signaling pathways. Among numerous ligands, laminin (LN) is known to promote neurite outgrowth and memory consolidation, while amyloid-beta oligomers (A beta o) trigger synaptic dysfunction. In both pathways, mGluR1 is recruited as co-receptor. The involvement of PrP (c)/mGluR1 in these opposite functions suggests that this complex is a key element in the regulation of synaptic activity. Considering that sleep-wake cycle is important for synaptic homeostasis, we aimed to investigate how sleep deprivation affects the expression of PrP (c) and its ligands, laminin, A beta o, and mGluR1, a multicomplex that can interfere with neuronal plasticity. To address this question, hippocampi of control (CT) and sleep deprived (SD) C57BL/6 mice were collected at two time points of circadian period (13 hr and 21 hr). We observed that sleep deprivation reduced PrP (c) and mGluR1 levels with higher effect in active state (21 hr). Sleep deprivation also caused accumulation of A beta peptides in rest period (13 hr), while laminin levels were not affected. In vitro binding assay showed that A beta o can compete with LN for PrP (c) binding. The influence of A beta o was also observed in neuritogenesis. LN alone promoted longer neurite outgrowth than non-treated cells in both Prnp(+/+) and Prnp(0/0) genotypes. A beta o alone did not show any effects, but when added together with LN, it attenuated the effects of LN only in Prnp(+/+) cells. Altogether, our findings indicate that sleep deprivation regulates the availability of PrP (c) and A beta peptides, and based on our in vitro assays, these alterations induced by sleep deprivation can negatively affect LN-PrP (c) interaction, which is known to play roles in neuronal plasticity. (AU)

• 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