Characterization of the Mitochondrial Aerobic Metabolism in the Pre- and Perisynaptic Districts of the SOD1 G93A Mouse Model of Amyotrophic Lateral Sclerosis

  • Silvia Ravera
  • Tiziana Bonifacino
  • Martina Bartolucci
  • Marco Milanese
  • Elena Gallia
  • Francesca Provenzano
  • Katia Cortese
  • Isabella Panfoli
  • Giambattista Bonanno


Amyotrophic lateral sclerosis (ALS) is an adult-onset fatal neurodegenerative disease characterized by muscle wasting, weakness, and spasticity due to a progressive degeneration of cortical, brainstem, and spinal motor neurons. The etiopathological causes are still largely obscure, although astrocytes definitely play a role in neuronal damage. Several mechanisms have been proposed to concur to neurodegeneration in ALS, including mitochondrial dysfunction. We have previously shown profound modifications of glutamate release and presynaptic plasticity in the spinal cord of the SOD1 G93A mouse model of ALS. In this work, we characterized, for the first time, the aerobic metabolism in two specific compartments actively involved in neurotransmission (i.e. the presynaptic district, using purified synaptosomes, and the perisynaptic astrocyte processes, using purified gliosomes) in SOD1 G93A mice at different stages of the disease. ATP/AMP ratio was lower in synaptosomes isolated from the spinal cord, but not from other brain areas, of SOD1 G93A vs. control mice. The energy impairment was linked to altered oxidative phosphorylation (OxPhos) and increment of lipid peroxidation. These metabolic dysfunctions were present during disease progression, starting at the very pre-symptomatic stages, and did not depend on a different number of mitochondria or a different expression of OxPhos proteins. Conversely, gliosomes showed a reduction of the ATP/AMP ratio only at the late stages of the disease and an increment of oxidative stress also in the absence of a significant decrement in OxPhos activity. Data suggest that the presynaptic neuronal moiety plays a pivotal role for synaptic energy metabolism dysfunctions in ALS. Changes in the perisynaptic compartment seem subordinated to neuronal damage.


Amyotrophic lateral sclerosis SOD1G93A mouse Oxidative phosphorylation Synaptosomes Gliosomes 



The authors are indebted to Mr. Giuseppe Marazzotta for his help in maintaining the SOD1 G93A and the wtSOD1 mouse colonies. The authors gratefully acknowledge the undergraduate students Cesare Cecchini, Mirna Nitro, and Roncallo Roberta, for their helpful technical support.


This work was supported by research grants from the Italian Ministry of University (PRIN Project No. 2016058401 to GB and SIR Project No. RBSI14B1Z to M.M.) and from the Motor Neuron Disease Association (Project No. April16/848-791) to GB.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Silvia Ravera
    • 1
  • Tiziana Bonifacino
    • 1
  • Martina Bartolucci
    • 2
  • Marco Milanese
    • 1
    • 3
  • Elena Gallia
    • 1
  • Francesca Provenzano
    • 1
  • Katia Cortese
    • 4
  • Isabella Panfoli
    • 2
  • Giambattista Bonanno
    • 1
    • 3
  1. 1.Department of Pharmacy, Unit of Pharmacology and ToxicologyUniversity of GenoaGenoaItaly
  2. 2.Department of Pharmacy, Laboratory of BiochemistryUniversity of GenoaGenoaItaly
  3. 3.Center of Excellence for Biomedical ResearchUniversity of GenoaGenoaItaly
  4. 4.Department of Experimental Medicine, Human AnatomyUniversity of GenoaGenoaItaly

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