Results making a significant contribution to understand the mechanisms of ALS neurodegeneration, and may providing insights to identify new targets for possible therapeutic manipulations

Following the project selected in 2011 by the Thierry Latran Foundation : What is the Origin of the Hyper-excitability of cortical and spinal motor neuron in ALS ? ( PI Daniel Zytnicki, CNRS, Paris) 

Cristina Zona, one of the co-applicants introduce her paper just published in Cerebral Cortex and titled:

“Altered Functionality, Morphology, and Vesicular Glutamate Transporter Expression of Cortical Motor Neurons from a Presymptomatic Mouse Model of Amyotrophic Lateral Sclerosis” 
by Saba L, Viscomi MT Caioli S, Pignataro A, Bisicchia E, Pieri M, Molinari M, Ammassari-Teule M and Zona C.

Despite various hypotheses about the responsible mechanisms, the etiology of ALS remains elusive, and the involvement of motor cortex in its pathophysiology is not completely understood. Notably in this work, for the first time, a primary role of the motor cortical area in the ALS pathology has been ascertained. In particular, early functional, morphological and biochemical alterations in cortical motor neurons from presymptomatic G93A mouse model of fALS have been outlined. Data reported in this study demonstrate changes in the cortical excitatory neurotransmission of primary  motor neurons, indicative of their hyperexcitability status, in association with an abnormal neuronal architecture and a higher expression level of an important protein involved in the signal transmission. The importance of this study has been to detect these cortical network abnormalities just in very presymptomatic mice, giving a strong support for the view that cortex plays a key role in the pathogenesis of ALS.

These results make a significant contribution to understand the mechanisms of ALS neurodegeneration, and may provide insights to identify new targets for possible therapeutic manipulations. “