الفهرس 
contentsOnly 14 pages are availabe for public view
 |  | from | 196 |  |  |
| | | from | 196 | | |
Abstract
PD is a progressive neurodegenartive disorder with extremely high psychosocial impacts and noticeable declines in patients’ quality of life. It’s defined by characteristic physical symptoms of bradykinesia, tremor, rigidity, and postural instability which are not obvious until approximate 70–80% of dopaminergic neurons are lost, suggesting that, there is a large population with asymptomatic early-stage disease for which currently there is no diagnosis. The cardinal biochemical abnormality in PD is the profound deficit in brain dopamine level attributed to the loss of dopaminergic neurons in the nigrostriatal system. While the pathological hallmarks of the disease are intracellular protein aggregates termed Lewy bodies, which are found in surviving neurons in the brains of PD patients. A common theme shared by PD and many other neurodegenerative disorders is the abnormal folding or clearance of potentially different cytotoxic protein species, including the ubiquitous presynaptic protein α-synuclein. Targeting α-synuclein aggregation is one of the main therapeutic approaches to develop disease-modifying agents. Heat shock proteins that can mediate the proper folding and refolding of client proteins, are vital to cell function and survival and thus have been explored as potential therapeutic agents. Important to PD, these molecules are capable of preventing α-synuclein misfolding and aggregation as shown in PD animal models. Furthermore, heat shock proteins are closely linked to pathways of protein degradation, like the ubiquitin-proteasome system and autophagy, and are thus able to remove irreversibly misfolded proteins.Therefore, one of the important strategies to remove the toxic protein aggregates from cells and to refold misfolded proteins, is to activate HSPs. Several strategies including physical exercise and phytochemicals (e.g., ferulic acid ) may induce HSPs in animal models of PDs. Therefore, upregulation of HSPs by these strategies is a promising therapeutic approach to relieve the adverse effect of accumulated misfolded proteins in several neurodegenerative diseases.In this study we investigated and compared the effects of exercise (Ex), ferulic acid (FR), and their combination on rotenone (ROT)-induced Parkinson disease (PD) in mice as well as the role of Hsp70 in this protective mechanisms. Thirty five male C57BL/6 mice were allocated into 5 groups, 1) Normal control (CTL) group, 2) ROT group (mice received ROT 3 mg/Kg i.p. for 70 days), 3) FR group (mice received ROT + FR at 20 mg/kg/day), 4) Ex group (mice received ROT + swimming Ex) and 5) FR+Ex group (mice received ROT + FR and Ex).Manual and software behavioral assessment of motor and exploratory behaviour were done using ANY-box behavioural tests at basal, 3, 5,7, and 10 weeks from the start of the experiment. Furthermore, after the end of experiment and scarifying of the mice, immunohisto-chemical examination of the dopaminergic system was done, using anti-TH antibody, anti- Hsp70 antibody and anti α-synuclein antibody. Conclusion: ROT- injection for 70 days in mice caused significant deteriorations in motor and exploratory behavior of mice. Also, ROT caused significant reduction in density of DAergic neurons (TH density) and in the expression of Hsp70 and formation of α-synuclein aggregates in corpus striatum which ensure development of PD model.