Multiple Layers of CDK5R1 Regulation in Alzheimer’s Disease Implicate Long Non-Coding RNAs

Cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) gene encodes for p35, the main activator of Cyclin-dependent kinase 5 (CDK5). The active p35/CDK5 complex is involved in numerous aspects of brain development and function, and its deregulation is closely associated to Alzheimer\u2019s disease (AD) onset and progression. We recently showed that miR-15/107 family can negatively regulate CDK5R1 expression modifying mRNA stability. Interestingly, miRNAs belonging to miR-15/107 family are downregulated in AD brain while CDK5R1 is upregulated. Long non-coding RNAs (lncRNAs) are emerging as master regulators of gene expression, including miRNAs, and their dysregulation has been implicated in the pathogenesis of AD. Here, we evaluated the existence of an additional layer of CDK5R1 expression regulation provided by lncRNAs. In particular, we focused on three lncRNAs potentially regulating CDK5R1 expression levels, based on existing data: NEAT1, HOTAIR, and MALAT1. We demonstrated that NEAT1 and HOTAIR negatively regulate CDK5R1 mRNA levels, while MALAT1 has a positive effect. We also showed that all three lncRNAs positively control miR-15/107 family of miRNAs. Moreover, we evaluated the expression of NEAT1, HOTAIR, and MALAT1 in AD and control brain tissues. Interestingly, NEAT1 displayed increased expression levels in temporal cortex and hippocampus of AD patients. Interestingly, we observed a strong positive correlation between CDK5R1 and NEAT1 expression levels in brain tissues, suggesting a possible neuroprotective role of NEAT1 in AD to compensate for increased CDK5R1 levels. Overall, our work provides evidence of another level of CDK5R1 expression regulation mediated by lncRNAs and points to NEAT1 as a biomarker, as well as a potential pharmacological target for AD therapy

Estudo da potenciação a longo prazo em fatias de hipocampo de ratos com epilepsia de curta, média e longa duração

30

Influência da epilepsia na potenciação de longa duração (LTP) em fatias hipocampais de ratos adultos

38

Environmental perception and activities in environmental education based on socio-ecological resilience

A concepção de ambiente para estudantes da educação básica e ensino médio foi obtida a partir da análise da percepção ambiental baseada em desenhos, enquanto as ações pró-ambientais mais importantes apontadas pelos estudantes foram capturadas por meio de um survey. Os dados de percepção ambiental e o nível das ações pró-ambientais foram correlacionados usando análise por componentes principais. A hipótese de que ações pró-ambientais significativas estão relacionadas com o nível de percepção ambiental foi confirmada. Portanto, atividades de ensino em educação ambiental baseada em resiliência sócio-ecológica são propostas para melhorar a percepção ambiental de estudantes e, consequentemente, conduzir a ações pró-ambientais efetivas