The cholesterol ester cycle regulates signalling complexes and synapse damage caused by amyloid-ß

Cholesterol is required for the formation and function of some signalling platforms. In synaptosomes, amyloid-β (Aβ) oligomers, the causative agent in Alzheimer's disease, bind to cellular prion proteins (PrPC) resulting in increased cholesterol concentrations, translocation of cytoplasmic phospholipase A2 (cPLA2, also known as PLA2G4A) to lipid rafts, and activation of cPLA2. The formation of Aβ-PrPC complexes is controlled by the cholesterol ester cycle. In this study, Aβ activated cholesterol ester hydrolases, which released cholesterol from stores of cholesterol esters and stabilised Aβ-PrPC complexes, resulting in activated cPLA2. Conversely, cholesterol esterification reduced cholesterol concentrations causing the dispersal of Aβ-PrPC complexes. In cultured neurons, the cholesterol ester cycle regulated Aβ-induced synapse damage; cholesterol ester hydrolase inhibitors protected neurons, while inhibition of cholesterol esterification significantly increased Aβ-induced synapse damage. An understanding of the molecular mechanisms involved in the dispersal of signalling complexes is important as failure to deactivate signalling pathways can lead to pathology. This study demonstrates that esterification of cholesterol is a key factor in the dispersal of Aβ-induced signalling platforms involved in the activation of cPLA2 and synapse degeneration

External Responsiveness of the SuperOpTM Device to Assess Recovery After Exercise : A Pilot Study

Post-exercise recovery is a complex process involving a return of performance and a physiological or perceptual feeling close to pre-exercise status. The hypothesis of this study is that the device investigated here is effective in evaluating the recovery state of professional cyclists in order to plan effective training. Ten professional male cyclists belonging to the same team were enrolled in this study. Participants performed a 7-day exercise program [D1, D4, and D7: low-intensity training; D2 and D5: passive recovery; D3: maximum oxygen consumption (VO2Max) test (for maximum mechanical power assessment only); and D6: constant load test]. During the week of monitoring, each morning before getting up, the device assessed each participant's so-called Organic Readiness {OR [arbitrary unit (a.u.)]}, based on blood pressure (BP), heart rate (HR), features of past exercise session, and following self-perceived condition. Based on its readings and algorithm, the device graphically displayed four different colors/values, indicating general exercise recommendations: green/3 = \u201cyou can train hard,\u201d yellow/2 = \u201cyou can train averagely,\u201d orange/1 = \u201cyou can train lightly,\u201d or red/0 = \u201cyou should recover passively.\u201d During the week of research, morning OR values and Bonferroni post-hoc comparisons showed significant differences between days and, namely, values (1) D2 (after low intensity training) was higher than D4 (after VO2Max test; P = 0.033 and d = 1.296) and (2) D3 and D6 (after passive recovery) were higher than D4 (after VO2Max test; P = 0.006 and d = 2.519) and D5 (after low intensity training; P = 0.033 and d = 1.341). The receiver operating characteristic analysis area under curve (AUC) recorded a result of 0.727 and could differentiate between D3 and D4 with a sensitivity and a specificity of 80%. Preliminarily, the device investigated is a sufficiently effective and sensitive/specific device to assess the recovery state of athletes in order to plan effective training

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

Neurotransmitter receptor trafficking during synaptic plasticity requires the concerted action of multiple signaling pathways and the protein transport machinery. However, little is known about the contribution of lipid metabolism during these processes. In this paper, we addressed the question of the role of cholesterol in synaptic changes during long-term potentiation (LTP). We found that N-methyl-d-aspartate-type glutamate receptor (NMDAR) activation during LTP induction leads to a rapid and sustained loss or redistribution of intracellular cholesterol in the neuron. A reduction in cholesterol, in turn, leads to the activation of Cdc42 and the mobilization of GluA1-containing α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) from Rab11-recycling endosomes into the synaptic membrane, leading to synaptic potentiation. This process is accompanied by an increase of NMDAR function and an enhancement of LTP. These results imply that cholesterol acts as a sensor of NMDAR activation and as a trigger of downstream signaling to engage small GTPase (guanosine triphosphatase) activation and AMPAR synaptic delivery during LTP.Peer Reviewe

Ruolo del colesterolo nella fisiologia delle sinapsi

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Educação sexual no ensino: uma sequência didática pelos caminhos do protagonismo dos alunos

Artigo Científico apresentado ao Curso Superior de Licenciatura em Ciências Biológicas, do Instituto Federal de Educação, Ciência e Tecnologia de Rondônia - Campus Colorado do Oeste, como requisito parcial para obtenção do título de Licenciada em Ciências Biológicas.A educação sexual no ambiente escolar é um assunto imprescindível a ser tratado para o desenvolvimento integral dos alunos e para a construção de uma sociedade informada e responsável. Este estudo analisa uma sequência didática voltada para a educação sexual, com o objetivo de promover o protagonismo dos alunos no processo de ensino aprendizagem. A pesquisa foi realizada em uma escola pública com alunos do ensino fundamental. A estrutura metodológica adota uma abordagem qualitativa, utilizando entrevistas estruturadas com professores e análise das atividades didáticas. A metodologia da sequência didática se baseia em teorias pedagógicas que valorizam o diálogo e a participação ativa dos alunos. Os resultados mostram que, apesar de desafios como resistências culturais e falta de formação dos professores, a educação sexual pode ampliar o conhecimento dos alunos e promover uma abordagem mais reflexiva sobre o cuidado com o corpo e a saúde. O estudo enriquece o debate sobre práticas pedagógicas inclusivas e destaca a importância de continuar investindo na formação docente e na integração da educação sexual no currículo escolar.Sex education in the school environment is an essential subject to be addressed for the integral development of students and for the construction of an informed and responsible society. This study analyzes a teaching sequence focused on sex education, with the objective of promoting the protagonism of students in the teaching-learning process. The research was conducted in a public school with elementary school students. The methodological framework adopts a qualitative approach, using structured interviews with teachers and analysis of teaching activities. The methodology of the teaching sequence is based on pedagogical theories that value dialogue and active participation of students. The results show that, despite challenges such as cultural resistance and lack of teacher training, teacher training, sex education can expand students' knowledge and promote a more reflective approach to caring for the body and health. The study enriches the debate on inclusive pedagogical practices and highlights the importance of continuing to invest in teacher training and the integration of sex education into the school curriculum