Highlights d Microglia lacking Rhoa become neurotoxic d Rhoa ablation in microglia leads to amyloidosis, synapse loss, and memory deficits d Rhoa ablation in microglia is sufficient to produce an AD-like pathology d Rhoa activation
Anthocyanins are naturally occurring polyphenols commonly found in fruits and vegetables. Numerous studies have described that anthocyanin-rich foods may play a crucial role in the prevention and treatment of different pathological conditions, which have encouraged their consumption around the world. Anthocyanins exhibit a significant neuroprotective role, mainly due to their well-recognized antioxidant and anti-inflammatory properties. Neuroinflammation is an intricate process relevant in both homeostatic and pathological circumstances. Since the progression of several neurological disorders relies on neuroinflammatory process, targeting brain inflammation has been considered a promising strategy in those conditions. Recent data have shown the anti-neuroinflammatory abilities of many anthocyanins and of their metabolites in the onset and development of several neurological disorders. In this review, it will be discussed the importance and the applicability of these polyphenolic compounds as neuroprotective agents and it will be also scrutinized the molecular mechanisms underlying the modulation of neuroinflammation by these natural compounds in the context of several brain diseases.
Alcohol abuse adversely affects the lives of millions of people worldwide. Deficits in synaptic transmission and in microglial function are commonly found in human alcohol abusers and in animal models of alcohol intoxication. Here, we found that a protocol simulating chronic binge drinking in male mice resulted in aberrant synaptic pruning and substantial loss of excitatory synapses in the prefrontal cortex, which resulted in increased anxiety-like behavior. Mechanistically, alcohol intake increased the engulfment capacity of microglia in a manner dependent on the kinase Src, the subsequent activation of the transcription factor NF-κB, and the consequent production of the proinflammatory cytokine TNF. Pharmacological blockade of Src activation or of TNF production in microglia, genetic ablation of Tnf, or conditional ablation of microglia attenuated aberrant synaptic pruning, thereby preventing the neuronal and behavioral effects of the alcohol. Our data suggest that aberrant pruning of excitatory synapses by microglia may disrupt synaptic transmission in response to alcohol abuse.
São várias as razões que tornam a aprendizagem de programação um processo difícil, ao qual as abordagens de ensino tradicionais não têm conseguido responder eficazmente. Muitas soluções tecnológicas têm sido desenvolvidas, porém o problema subsiste. Para além de diversas razões apontadas por muitos autores como estando na origem deste problema, destacamos a elevada dificuldade apresentada pelos alunos para resolver problemas genéricos. Esta dificuldade é acentuada quando os problemas são mais orientados à programação, traduzindo-se na incapacidade de concepção de algoritmos. Encontra-se em desenvolvimento uma nova proposta que se centra essencialmente no desenvolvimento de competências de resolução de problemas, genéricos numa fase de conhecimento inicial e orientados à programação em fases cognitivas mais avançadas. Este novo ambiente assenta em duas estruturas basilares, os estilos de aprendizagem preferenciais de cada aluno e o seu nível cognitivo. Relativamente a este último aspecto incorpora também mecanismos para treinar as funções cognitivas em défice.
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