PMID- 29656361
OWN - NLM
STAT- MEDLINE
DCOM- 20190118
LR  - 20210109
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 55
IP  - 12
DP  - 2018 Dec
TI  - Characterization of the Mitochondrial Aerobic Metabolism in the Pre- and 
      Perisynaptic Districts of the SOD1(G93A) Mouse Model of Amyotrophic Lateral 
      Sclerosis.
PG  - 9220-9233
LID - 10.1007/s12035-018-1059-z [doi]
AB  - 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.
FAU - Ravera, Silvia
AU  - Ravera S
AD  - Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, 
      16148, Genoa, Italy.
FAU - Bonifacino, Tiziana
AU  - Bonifacino T
AD  - Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, 
      16148, Genoa, Italy.
FAU - Bartolucci, Martina
AU  - Bartolucci M
AD  - Department of Pharmacy, Laboratory of Biochemistry, University of Genoa, 16132, 
      Genoa, Italy.
FAU - Milanese, Marco
AU  - Milanese M
AD  - Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, 
      16148, Genoa, Italy.
AD  - Center of Excellence for Biomedical Research, University of Genoa, 16132, Genoa, 
      Italy.
FAU - Gallia, Elena
AU  - Gallia E
AD  - Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, 
      16148, Genoa, Italy.
FAU - Provenzano, Francesca
AU  - Provenzano F
AD  - Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, 
      16148, Genoa, Italy.
FAU - Cortese, Katia
AU  - Cortese K
AD  - Department of Experimental Medicine, Human Anatomy, University of Genoa, 16132, 
      Genoa, Italy.
FAU - Panfoli, Isabella
AU  - Panfoli I
AD  - Department of Pharmacy, Laboratory of Biochemistry, University of Genoa, 16132, 
      Genoa, Italy.
FAU - Bonanno, Giambattista
AU  - Bonanno G
AUID- ORCID: 0000-0003-3744-5786
AD  - Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, 
      16148, Genoa, Italy. bonanno@difar.unige.it.
AD  - Center of Excellence for Biomedical Research, University of Genoa, 16132, Genoa, 
      Italy. bonanno@difar.unige.it.
LA  - eng
GR  - PRIN project n. 2016058401/Italian Ministry of University/
GR  - SIR project n. RBSI14B1Z/Italian Ministry of University/
GR  - project n. April16/848-791/Motor Neurone Disease Association/United Kingdom
PT  - Journal Article
DEP - 20180414
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Mitochondrial Proteins)
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
SB  - IM
MH  - Adenosine Monophosphate/metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Aerobiosis
MH  - Amyotrophic Lateral Sclerosis/*metabolism/pathology
MH  - Animals
MH  - Brain/metabolism
MH  - Disease Models, Animal
MH  - Energy Metabolism
MH  - Humans
MH  - Lipid Peroxidation
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitochondria/*metabolism/ultrastructure
MH  - Mitochondrial Proteins/metabolism
MH  - Neuroglia/metabolism
MH  - Oxygen Consumption
MH  - Spinal Cord/metabolism
MH  - Superoxide Dismutase-1/*metabolism
MH  - Synapses/*metabolism/ultrastructure
MH  - Synaptosomes/metabolism/ultrastructure
OTO - NOTNLM
OT  - Amyotrophic lateral sclerosis
OT  - Gliosomes
OT  - Oxidative phosphorylation
OT  - SOD1 G93A mouse
OT  - Synaptosomes
EDAT- 2018/04/16 06:00
MHDA- 2019/01/19 06:00
CRDT- 2018/04/16 06:00
PHST- 2017/12/27 00:00 [received]
PHST- 2018/04/03 00:00 [accepted]
PHST- 2018/04/16 06:00 [pubmed]
PHST- 2019/01/19 06:00 [medline]
PHST- 2018/04/16 06:00 [entrez]
AID - 10.1007/s12035-018-1059-z [pii]
AID - 10.1007/s12035-018-1059-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2018 Dec;55(12):9220-9233. doi: 10.1007/s12035-018-1059-z. Epub 
      2018 Apr 14.