Differential proteome of the striatum from hemiparkinsonian rats displays vivid structural remodeling processes.
Parkinson's disease is a multifactorial, neurodegenerative disease where etiopathogenetic mechanisms are not fully understood. Animal models like the neurotoxic 6-OHDA-hemiparkinsonian rat model are used for standardized experiments. Here, we analyzed proteome changes of the striatum three months after 6-OHDA lesions of the nigral dopaminergic cell population. Striata were removed and proteins were separated by 2DE followed by differential spot analysis. Proteins in spots were identified by MALDI-TOF-MS. Most up-regulations of proteins were concerning energy metabolism in mitochondria. Proteins of calcium homeostasis like annexin A3, annexin A7, calbindin, calmodulin, calreticulin, and reticulocalbin 1 also were differentially regulated. Moreover, proteins involved in antioxidative mechanisms like superoxide dismutase, protein disulfide isomerase 1 and 3, N(G),N(G)-dimethylarginindimethyl-aminotransferase 2, and thioredoxin-dependent peroxide reductase were up-regulated. Interestingly, most cytoskeletal proteins belonging to the axon cytoskeleton and synapse were up-regulated pointing to long-distance axon remodeling. In addition, transcription factors, proteins of nucleic acid metabolism, chaperones, and degrading proteins (UCHL1) were up-regulated as well. In conclusion, the neurotoxin-induced proteome alterations indicate vivid long-distance remodeling processes of dendrites, axons, and synapses that are still ongoing even three months after perturbation, indicating a high plasticity and regeneration potential in the adult rat brain.
Lessner
Grit
G
Department of Anatomy, Gertrudenstrasse 9, 18055 Rostock, Germany.
Schmitt
Oliver
O
Haas
Stefan J-P
SJ
Mikkat
Stefan
S
Kreutzer
Michael
M
Wree
Andreas
A
Glocker
Michael O
MO
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D007150:Immunohistochemistry; D008297:Male; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D020543:Proteome / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D020543:Proteome; D016627:Oxidopamine; D002118:Calcium