Differential Proteome of the Striatum from Hemiparkinsonian Rats Displays Vivid Structural Remodeling Processes

Abstract

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.

MicroRNA-7 Regulates the Function of Mitochondrial Permeability Transition Pore by Targeting VDAC1 Expression

“…VDAC1 protein and mRNA levels were reported to be elevated following administration of mitochondrial complex I inhibitors, such as rotenone and MPP ϩ (26,27). VDAC1 expression was also increased in striatal extracts of 6-hydroxydopamine-treated rats (35). Another study reported that VDAC1 protein level is elevated in the striatum and cortex of parkin null mice (36).…”

Reduced Calreticulin Levels Link Endoplasmic Reticulum Stress and Fas-Triggered Cell Death in Motoneurons Vulnerable to ALS

“…In particular, laser-captured motoneurons from presymptomatic mSOD1 mice showed a 30% decrease in CRT mRNA (Perrin et al, 2005) and reduced CRT protein levels are apparent in symptomatic mSOD1 spinal cord (Teuling et al, 2007). Moreover, CRT is downregulated in cortical neurons of Alzheimer's patient brains (Taguchi et al, 2000) and in striatal neurons of hemiparkinsonian rats (Lessner et al, 2010). Although no functional studies were carried out, it is striking that ER stress is activated in all the above contexts (Wang and Takahashi, 2007;Lee et al, 2010;Lessner et al, 2010).…”

“…Moreover, CRT is downregulated in cortical neurons of Alzheimer's patient brains (Taguchi et al, 2000) and in striatal neurons of hemiparkinsonian rats (Lessner et al, 2010). Although no functional studies were carried out, it is striking that ER stress is activated in all the above contexts (Wang and Takahashi, 2007;Lee et al, 2010;Lessner et al, 2010). Reductions in CRT may therefore play a general role in neurodegeneration.…”

Differential Proteomics of the Cerebral Cortex of Juvenile, Adult and Aged Rats: An Ontogenetic Study

“…The extraction of proteins was performed according to published standardized protocols [26,30,31]. In the following the steps are described shortly.…”

“…Several studies [24][25][26] focus on the transplantation of immortalized progenitor cells in 6-OHDA Hemiparkinson animal models [24,25] and the differences in the abundance of this area of the brain at different points of development [26]. Hovakimyan et al [24] and Haas et al [25] as well as Schwarz and Freed [27] showed that the micro-environment of neonatal brains seems to be important for the differentiation of transplanted neuronal progenitors.…”