Cortical synaptic and dendritic spine abnormalities in a presymptomatic TDP-43 model of amyotrophic lateral sclerosis
| Autor: | Matthew J. Fogarty, Shyuan T. Ngo, Mark C. Bellingham, John D. Lee, Peter G. Noakes, Paul M. Klenowski, Selena E. Bartlett, Joy R. Drieberg-Thompson, Massimo A. Hilliard |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Dendritic spine Dendritic Spines Excitotoxicity Neural degeneration Neurotransmission Biology medicine.disease_cause Synaptic Transmission Article Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Patch clamp Amyotrophic lateral sclerosis Cells Cultured Mice Knockout Multidisciplinary Pyramidal Cells Amyotrophic Lateral Sclerosis Motor Cortex Excitatory Postsynaptic Potentials medicine.disease DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Nerve Degeneration Synapses Excitatory postsynaptic potential Female 030217 neurology & neurosurgery Motor cortex |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep37968 |
| Popis: | Layer V pyramidal neurons (LVPNs) within the motor cortex integrate sensory cues and co-ordinate voluntary control of motor output. In amyotrophic lateral sclerosis (ALS) LVPNs and spinal motor neurons degenerate. The pathogenesis of neural degeneration is unknown in ALS; 10% of cases have a genetic cause, whereas 90% are sporadic, with most of the latter showing TDP-43 inclusions. Clinical and experimental evidence implicate excitotoxicity as a prime aetiological candidate. Using patch clamp and dye-filling techniques in brain slices, combined with high-resolution confocal microscopy, we report increased excitatory synaptic inputs and dendritic spine densities in early presymptomatic mice carrying a TDP-43Q331K mutation. These findings demonstrate substantive alterations in the motor cortex neural network, long before an overt degenerative phenotype has been reported. We conclude that increased excitatory neurotransmission is a common pathophysiology amongst differing genetic cases of ALS and may be of relevance to the 95% of sporadic ALS cases that exhibit TDP-43 inclusions. |
| Databáze: | OpenAIRE |
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