Pyramidal cell axon initial segment in Alzheimer´s disease

The axon initial segment (AIS) is a region of the neuron that is critical for action potential generation as well as for the regulation of neural activity. This specialized structure—characterized by the expression of different types of ion channels as well as adhesion, scaffolding and cytoskeleton...

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Detalhes bibliográficos
Autores: Antón Fernández, Alejandro, León Espinosa, Gonzalo, DeFelipe, Javier, Muñoz Céspedes, Alberto
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/123806
Acesso em linha:https://hdl.handle.net/20.500.14352/123806
Access Level:acceso abierto
Palavra-chave:576
612.8
616.894-053.9
612.822
Biología celular (Biología)
Neurociencias (Biológicas)
2407 Biología Celular
2490 Neurociencias
3207.11 Neuropatología
2411.12 Fisiología del Sistema Nervioso Central
Descrição
Resumo:The axon initial segment (AIS) is a region of the neuron that is critical for action potential generation as well as for the regulation of neural activity. This specialized structure—characterized by the expression of different types of ion channels as well as adhesion, scaffolding and cytoskeleton proteins—is subjected to morpho-functional plastic changes in length and position upon variations in neural activity or in pathological conditions. In the present study, using immunocytochemistry with the AT8 antibody (phospho-tau S202/T205) and 3D confocal microscopy reconstruction techniques in brain tissue from Alzheimer’s disease patients, we found that around half of the cortical pyramidal neurons with hyperphosphorylated tau showed changes in AIS length and position in comparison with AT8-negative neurons from the same cortical layers. We observed a wide variety of AIS alterations in neurons with hyperphosphorylated tau, although the most common changes were a proximal shift or a lengthening of the AISs. Similar results were found in neocortical tissue from non-demented cases with neurons containing hyperphosphorylated tau. These findings support the notion that the accumulation of phospho-tau is associated with structural alterations of the AIS that are likely to have an impact on normal neuronal activity, which might contribute to neuronal dysfunction in AD.