Proteomic profiling of cervical and lumbar spinal cord reveals potential protective mechanisms in the wobbler mouse, a model of motor neuron degeneration.
The wobbler mouse is a model of selective motor neuron degeneration in the cervical spinal cord. Comparing cervical and lumbar tracts of control and diseased mice at the early stage of pathology by proteomic analysis, we identified 31 proteins by peptide mass fingerprint after tryptic digestion and MALDI-TOF analysis, that were differently represented among the four experimental groups. In healthy mice, patterns of protein expression differed between cervical and lumbar tract: proteins of cellular energetic metabolism pathway showed lower expression in the cervical tract, while cellular trafficking proteins were overrepresented. In wobbler mice, these differences disappeared and the expression pattern was similar between cervical and lumbar spinal cord. We found that most of the proteins differentially regulated in wobbler with respect to control cervical tract were related to astrogliosis or involved in glutamate-glutamine cycle, energy transduction and redox functions. Proteins overrepresented in the wobbler lumbar spinal cord were cytoskeleton proteins and cellular transport proteins, in particular the vesicle fusing ATPase and the isoform 2 of syntaxin-binding protein 1, involved in vesicle trafficking. We suggest that overexpression of proteins involved in vesicle trafficking, together with proteins counteracting mitochondrial dysfunction can have neuroprotective effects, preserving lumbar spinal cord motor neurons in wobbler mice.
Bastone
Antonio
A
Department of Biochemistry and Molecular Pharmacology, Mario Negri Institute for Pharmacological Research, Milano, Italy. antonio.bastone@marionegri.it
Fumagalli
Elena
E
Bigini
Paolo
P
Perini
Pietro
P
Bernardinello
Davide
D
Cagnotto
Alfredo
A
Mereghetti
Ilario
I
Curti
Daniela
D
Salmona
Mario
M
Mennini
Tiziana
T
D000818:Animals; D002574:Cervical Vertebrae; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008159:Lumbar Vertebrae; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D010101:Oxygen Consumption; D020543:Proteome / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
D009419:Nerve Tissue Proteins; D020543:Proteome