A carregar...
Publicação
Inhibitory circuitry in motor neuron disease : changes in spinal and corticospinal mechanisms in amyotrophic lateral sclerosis and its variants
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 4.72 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
A Esclerose Lateral Amiotrófica (ELA) é uma doença neurodegenerativa rapidamente progressiva que principalmente afeta os neurónios motores da medula espinal, do tronco cerebral, e do córtex. Deste processo resulta a gradual perda da função motora e da capacidade respiratória, em geral originando a morte poucos anos após os primeiros sintomas. Apesar de décadas de intensa investigação, a etiopatogenia desta doença permanece elusiva, não existindo atualmente cura para esta doença devastadora. A origem da ELA é extraordinariamente complexa, envolvendo uma intricada interação de fatores genéticos, ambientais e celulares. Entre os aspetos multifacetados que contribuem para o início e progressão da doença, o papel dos mecanismos inibitórios espinhais e supraespinhais é uma área de investigação fascinante. Estes mecanismos desempenham um papel crucial, mas ainda não completamente compreendido, na modulação da excitabilidade dos neurónios motores e na integridade dos circuitos motores, influenciando assim o início e progressão da ELA. Há uma significativa quantidade de evidências de estudos em animais, in vitro, histopatológicos, imagem e neurofisiológicos que implicam mecanismos inibitórios corticais, principalmente controlados por interneurónios GABAérgicos e glicinérgicos, na fisiopatologia da ELA. A disfunção do controle inibitório da excitabilidade dos motoneurónios contribui para, e possivelmente origina, a típica degeneração do sistema motor. Em relação ao controle da função motora a nível segmentar da medula espinhal, esses mecanismos estão menos estudados na ELA, apesar de seu potencial relevante papel na fisiopatologia desta doença.
Amyotrophic Lateral Sclerosis (ALS) is a relentlessly progressive and devastating neurodegenerative disorder that primarily affects motor neurons within the spinal cord, brainstem and brain. This debilitating condition culminates in the gradual loss of motor function, leading to muscle weakness, atrophy, and eventually paralysis, typically with a fatal outcome within a few years after the first symptoms. Despite decades of research, the precise etiology of ALS remains elusive, and there is currently no cure for this devastating disease. The pathophysiology of ALS is extraordinarily complex, involving an intricate interplay of genetic, environmental, and cellular factors. Among the multifaceted aspects contributing to the disease's onset and progression, the role of inhibitory spinal and supraspinal mechanisms is a compelling area of investigation. These mechanisms play a pivotal yet still not completely understood role in modulating the excitability of motor neurons and the integrity of motor circuits, thereby influencing the manifestation and progression of ALS. There is an accumulated amount of evidence from animal, in vitro, histopathological, imaging, and neurophysiological studies implying cortical inhibitory mechanisms, mainly controlled by GABAergic and glycinergic interneurons, in ALS pathophysiology. The pathological decrease in inhibitory control of motoneurons excitability contributes, and possibly leads, to characteristic degeneration of the motor system. Regarding segmental spinal control of motor function, these mechanisms are much less studied in ALS, despite their possible significant role to the pathophysiology of this disease.
Amyotrophic Lateral Sclerosis (ALS) is a relentlessly progressive and devastating neurodegenerative disorder that primarily affects motor neurons within the spinal cord, brainstem and brain. This debilitating condition culminates in the gradual loss of motor function, leading to muscle weakness, atrophy, and eventually paralysis, typically with a fatal outcome within a few years after the first symptoms. Despite decades of research, the precise etiology of ALS remains elusive, and there is currently no cure for this devastating disease. The pathophysiology of ALS is extraordinarily complex, involving an intricate interplay of genetic, environmental, and cellular factors. Among the multifaceted aspects contributing to the disease's onset and progression, the role of inhibitory spinal and supraspinal mechanisms is a compelling area of investigation. These mechanisms play a pivotal yet still not completely understood role in modulating the excitability of motor neurons and the integrity of motor circuits, thereby influencing the manifestation and progression of ALS. There is an accumulated amount of evidence from animal, in vitro, histopathological, imaging, and neurophysiological studies implying cortical inhibitory mechanisms, mainly controlled by GABAergic and glycinergic interneurons, in ALS pathophysiology. The pathological decrease in inhibitory control of motoneurons excitability contributes, and possibly leads, to characteristic degeneration of the motor system. Regarding segmental spinal control of motor function, these mechanisms are much less studied in ALS, despite their possible significant role to the pathophysiology of this disease.
Descrição
Tese de doutoramento em Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2024
Palavras-chave
Amyotrophic lateral sclerosis Motor neuron disease Interneurons Inhibitory circuits Segmental spinal inhibition Cortical inhibition Esclerose lateral amiotrófica doença do neurónio motor Interneurónios Circuitos inibitórios inibição espinhal segmentar Inibição cortical