title: Protection of MPTP-induced neuroinflammation and neurodegeneration by rotigotine-loaded microspheres.
abstract: OBJECTIVE
  The aim of the study is to evaluate the neuroprotective effects of continuous dopaminergic stimulation (CDS) by rotigotine-loaded microspheres (RoMS) in a mouse model of MPTP-induced Parkinson's disease (PD) and to elucidate the potential mechanism underlying these effects.
  
  
  METHODS
  Male C57BL/6 mice were treated either intramuscularly once with RoMS or twice daily for two weeks with rotigotine, and from the 9th day, MPTP (30 mg/kg, i.p.) was injected for the last 5 days. Following treatment, Parkinsonism scores were calculated and oxidative stress-related indicators in the striatum were performed. Neuroinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were detected in the striatum. Expression of apoptosis-related proteins B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) was measured in the striatum by Western blot. Nigral tyrosine hydroxylase (TH)-positive neurons and microglial cell markers, i.e., ionized calcium binding adaptor molecule-1 (Iba-1) and neuronal synaptosomes, were quantified to assess the neuroprotective efficacy of RoMS.
  
  
  RESULTS
  The administration of rotigotine significantly improved the Parkinsonism score, protected dopaminergic neurons with antioxidants, reduced microglial cell activation and the release of neuroinflammatory cytokines, and balanced the expression of Bcl-2 and Bax in MPTP-treated mice. Interestingly, the neuroprotective properties of rotigotine were remarkably amplified by CDS treatment with RoMS.
  
  
  CONCLUSIONS
  These results suggest that CDS therapy can play a neuroprotective role in an MPTP mouse model. Neuroprotective disease-modifying therapy may have the potential benefits of early treatment by normalizing compensatory mechanisms and may also help to delay dyskinesia in the later stages of PD.
authors: School of Pharmacy, Yantai University, Yantai 264005, PR China. Electronic address: xin523@sina.com.
authors: Xin
authors: X
authors: Yu
authors: School of Pharmacy, Yantai University, Yantai 264005, PR China.
authors: Jun-Yi
authors: JY
authors: Yao
authors: State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies, Yantai 264003, PR China.
authors: Jie
authors: J
authors: He
authors: School of Pharmacy, Yantai University, Yantai 264005, PR China; State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies, Yantai 264003, PR China. Electronic address: Tianjingwei@luye.cn.
authors: Jing-Wei
authors: JW
authors: Tian
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D020267:MPTP Poisoning / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: Continuous dopaminergic stimulation; Neuroprotection; Parkinson's disease; Rotigotine-loaded microspheres