Synapse Dysfunction of Layer V Pyramidal Neurons Precedes Neurodegeneration in a Mouse Model of TDP-43 Proteinopathies
作者： Emily E. Handley , Kimberley A. Pitman , Edgar Dawkins , Kaylene M. Young , Rosemary M. Clark
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摘要: TDP-43 is a major protein component of pathological neuronal inclusions that are present in frontotemporal dementia and amyotrophic lateral sclerosis. We report plays an important role dendritic spine formation the cortex. The density spines on YFP+ pyramidal neurons both motor somatosensory cortex Thy1-YFP mice, increased significantly from postnatal day 30 (P30), to peak at P60, before being pruned by P90. By comparison, was reduced Thy1-YFP::TDP-43A315T transgenic mice prior symptom onset (P60), (P90). Morphological spine-type analysis revealed there significant impairment development basal mushroom compared control. Furthermore, reductions corresponded mislocalisation immunoreactivity lowered efficacy synaptic transmission as determined electrophysiology P60. conclude mutated has effect associated with attenuated neural transmission.
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