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...
| Autores: | , , , |
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| 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 |
| 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. |
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