Human neuromuscular junction three-dimensional organoid models and the insight in motor disorders

The neuromuscular junction(NMJ),a peripheral synaptic connection between motoneurons and skeletal muscle fibers,controls movement.Dysregulation of NMJs has been implicated in various motor disorders.Because of their large size and easy accessibility,NMJs have been extensively investigated in the neuroscience field and have greatly contributed to our understanding of the fundamental principles of synapses in the central nervous system.Researchers have tried multiple ways to develop models to recreate NMJs.Rapid progress in the research and development of tissue-like organoids has made it possible to produce human NMJ three-dimensional(3D)models in vitro,providing an additional powerful strategy to study NMJs.Here,we introduce the most recent advances of human embryonic stem cell-or induced pluripotent stem cell-derived organoids to model 3D NMJs.

Prevalence and Characterization of the Cerebral Palsy in Maceio,a Northeast City of Brazil

Background: Cerebral palsy is a group of disorders arising from a static damage or brain development defects occurring during fetal life and in the first months of life. Methods: The sample consisted of 800 individuals living in 50 districts of the city of Maceio. A standardized questionnaire was applied. Results: The prevalence of cerebral palsy in the sample was 5/1000. All were born at term, 75% were male, 50% had severe cerebral palsy and 50% was moderate. 75% had quadriplegia and 25% had diplegia. Fifty percent of the cerebral palsy was caused by meningitis and 50% for prolonged labor. Conclusions: The prevalence of cerebral palsy in Maceió is 140.38% higher than the highest prevalence found in developed countries, predominantly in low-income and related to postnatal infection in families.

Quercetin prevents spinal motor neuron degeneration induced by chronic excitotoxic stimulus by a sirtuin 1-dependent mechanism

Background:Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders.Effective therapeutic strategies are an unmet need for these disorders.Polyphenols,such as quercetin and resveratrol,are plant-derived compounds that activate sirtuins(SIRTs)and have shown promising results in some models of neuronal death,although their effects have been scarcely tested in models of motor neuron degeneration.Methods:In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion ofα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA)into the rat spinal cord tissue.Quercetin and resveratrol were co-infused with AMPA and motor behavior and muscle strength were assessed daily for up to ten days.Then,animals were fixed and lumbar spinal cord tissue was analyzed by histological and immunocytological procedures.Results:We found that the chronic infusion of AMPA[1 mM]caused a progressive motor neuron degeneration,accompanied by astrogliosis and microgliosis,and motor deficits and paralysis of the rear limbs.Quercetin infusion ameliorated AMPA-induced paralysis,rescued motor neurons,and prevented both astrogliosis and microgliosis,and these protective effects were prevented by EX527,a very selective SIRT1 inhibitor.In contrast,neither resveratrol nor EX527 alone improved motor behavior deficits or reduced motor neuron degeneration,albeit both reduced gliosis.Conclusions:These results suggest that quercetin exerts its beneficial effects through a SIRT1-mediated mechanism,and thus SIRT1 plays an important role in excitotoxic neurodegeneration and therefore its pharmacological modulation might provide opportunities for therapy in motor neuron disorders.