Synaptic remodeling follows upper motor neuron hyperexcitability in a rodent model of TDP-43.

ABSTRACT: Amyotrophic Lateral Sclerosis (ALS) is an incurable disease characterized by relentlessly progressive degeneration of the corticomotor system. Cortical hyperexcitability has been identified as an early pre-symptomatic biomarker of ALS. This suggests that hyperexcitability occurs upstream in the ALS pathological cascade and may even be part of the mechanism that drives development of symptoms or loss of motor neurons in the spinal cord. However, many studies also indicate a loss to the synaptic machinery that mediates synaptic input which raises the question of which is the driver of disease, and which is a homeostatic response. Herein, we used an inducible mouse model of TDP-43 mediated ALS that permits for the construction of detailed phenotypic timelines. Our work comprehensively describ

SUBMITTER: Dyer MS 

PROVIDER: S-EPMC10628445 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature