A carregar...
Publicação
Bioenergetics and metabolism in neural regeneration
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 1018.69 KB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
De acordo com a evidência atual, o sistema nervoso e especialmente o cérebro, têm
uma elevada procura energética. Em condições normais, a bioenergética neuronal está
bem definida, sendo aceite que o cérebro recorre à glucose como principal fonte
energética. No entanto, na ausência de glucose, é necessário recorrer a substratos
diferentes, tais como lactato, glicogénio, corpos cetónicos e ácidos gordos.
A regeneração neuronal no SNC é bastante limitada por mecanismos intrínsecos e
por fatores externos, em comparação à regeneração no SNP. Após uma lesão, os
neurónios danificados precisam de ser regenerados e os perdidos têm de ser repostos
através da neurogénese. Ambos os processos requerem largas quantidades de energia,
por isso é crucial esclarecer os mecanismos metabólicos que permitem uma produção
suficiente de energia para suportar a regeneração e os fatores condicionantes desse
processo.
A neurogénese descreve a formação de novos neurónios, através da ativação,
proliferação e diferenciação de células estaminais neuronais. Normalmente, econtramse quiescentes e dependentes de um perfil metabólico específico para manter as funções
e características. Durante a neurogénese, os atributos e as necessidades metabólicas das
células estaminais neuronais alteram-se, bem como as suas fontes energéticas.
Um aspeto promissor das células estaminais neuronais é a sua utilização em
enxertos para ajudar na recuperação de tecidos danificados, não só pela formação de
novas células mas também pela secreção de fatores de crescimento e outras moléculas
ativas que atuam nas células circundantes para promover a regeneração neuronal. A
transferência recentemente descrita entre neurónios pode salvar células disfuncionais e
potencialmente aumentar a regeneração.
Nesta monografia, são abordadas as principais fontes de energeia no cérebro, os
processos inerentes à regeneração neuronal e como são suportados metabolicamente.
Por ultimo, é explicado o papel essencial das células estaminias neuronais e o seu perfil
metabólico juntamente com alguns factores que afetam a plasticidade neuronal
According to the current evidence, the nervous system and especially the brain has a high energetic demand. In regular conditions, neuronal bioenergetics are well defined, being generally accepted that the brain resorts to glucose as the principal energetic source. Nonetheless, in the absence of glucose or in increased energetic requirements, it is necessary to resort to alternative fuels such as lactate, glycogen, ketone bodies and fatty acids. Neural regeneration in the central nervous system of adult humans is severely impaired, both by intrinsic mechanisms and by extrinsic factors, when compared to the regeneration that occurs in peripheral nervous system neurons. Upon an injury, damaged neurons must be regenerated, and lost ones need to be replaced by neurogenesis. These processes have enormous energetic requirements, so it is crucial to clarify the metabolic mechanisms that allows cells to produce sufficient energy to regenerate and what factors can affect this process. Neurogenesis describes the formation of new neurons through activation, proliferation and differentiation of NSCs. Normally, NSCs are in a quiescent state that depends on a specific metabolic profile to maintain functions and the characteristic properties. During the various steps of neurogenesis, NSCs attributes and metabolic needs changes, as well as their energetic sources to ensure enough ATP is provided. A promising aspect of NSCs is their utilization in grafts to help with damaged tissue regeneration, not only by proliferation and differentiation but also by secreting growth factors and other active molecules that act on the surrounding cells to promote neuroregeneration. The recently described mitochondrial exchange between CNS neurons can rescue dysfunctional cells and enhance regeneration. The principal energy sources in the brain, the axonal regeneration processes and how they are metabolically supported are addressed in this thesis. Lastly, it is explained the fundamental role of NSCs and their metabolic prolife in neuroregeneration along with some factors that affected neuronal plasticity.
According to the current evidence, the nervous system and especially the brain has a high energetic demand. In regular conditions, neuronal bioenergetics are well defined, being generally accepted that the brain resorts to glucose as the principal energetic source. Nonetheless, in the absence of glucose or in increased energetic requirements, it is necessary to resort to alternative fuels such as lactate, glycogen, ketone bodies and fatty acids. Neural regeneration in the central nervous system of adult humans is severely impaired, both by intrinsic mechanisms and by extrinsic factors, when compared to the regeneration that occurs in peripheral nervous system neurons. Upon an injury, damaged neurons must be regenerated, and lost ones need to be replaced by neurogenesis. These processes have enormous energetic requirements, so it is crucial to clarify the metabolic mechanisms that allows cells to produce sufficient energy to regenerate and what factors can affect this process. Neurogenesis describes the formation of new neurons through activation, proliferation and differentiation of NSCs. Normally, NSCs are in a quiescent state that depends on a specific metabolic profile to maintain functions and the characteristic properties. During the various steps of neurogenesis, NSCs attributes and metabolic needs changes, as well as their energetic sources to ensure enough ATP is provided. A promising aspect of NSCs is their utilization in grafts to help with damaged tissue regeneration, not only by proliferation and differentiation but also by secreting growth factors and other active molecules that act on the surrounding cells to promote neuroregeneration. The recently described mitochondrial exchange between CNS neurons can rescue dysfunctional cells and enhance regeneration. The principal energy sources in the brain, the axonal regeneration processes and how they are metabolically supported are addressed in this thesis. Lastly, it is explained the fundamental role of NSCs and their metabolic prolife in neuroregeneration along with some factors that affected neuronal plasticity.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Neural metabolism Mitochondria Axonal regeneration Neurogenesis Neural stem cells Mestrado integrado - 2021