title: Updates in the pathophysiological mechanisms of Parkinson's disease: Emerging role of bone marrow mesenchymal stem cells.
abstract: OBJECTIVE
  To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson's disease (PD) pathophysiology.
  
  
  METHODS
  MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.
  
  
  RESULTS
  BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.
  
  
  CONCLUSIONS
  The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.
authors.affiliation: Hanaa H Ahmed, Emad F Eskandar, Hadeer A Aglan, Hormones Department, Medical Research Division, National Research Centre, Giza 12622, Egypt.
authors.forename: Hanaa H
authors.initials: HH
authors.lastname: Ahmed
authors.affiliation: Hanaa H Ahmed, Emad F Eskandar, Hadeer A Aglan, Hormones Department, Medical Research Division, National Research Centre, Giza 12622, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Salem
authors.affiliation: Hanaa H Ahmed, Emad F Eskandar, Hadeer A Aglan, Hormones Department, Medical Research Division, National Research Centre, Giza 12622, Egypt.
authors.forename: Hazem M
authors.initials: HM
authors.lastname: Atta
authors.affiliation: Hanaa H Ahmed, Emad F Eskandar, Hadeer A Aglan, Hormones Department, Medical Research Division, National Research Centre, Giza 12622, Egypt.
authors.forename: Emad F
authors.initials: EF
authors.lastname: Eskandar
authors.affiliation: Hanaa H Ahmed, Emad F Eskandar, Hadeer A Aglan, Hormones Department, Medical Research Division, National Research Centre, Giza 12622, Egypt.
authors.forename: Abdel Razik H
authors.initials: AR
authors.lastname: Farrag
authors.affiliation: Hanaa H Ahmed, Emad F Eskandar, Hadeer A Aglan, Hormones Department, Medical Research Division, National Research Centre, Giza 12622, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ghazy
authors.affiliation: Hanaa H Ahmed, Emad F Eskandar, Hadeer A Aglan, Hormones Department, Medical Research Division, National Research Centre, Giza 12622, Egypt.
authors.forename: Neveen A
authors.initials: NA
authors.lastname: Salem
authors.affiliation: Hanaa H Ahmed, Emad F Eskandar, Hadeer A Aglan, Hormones Department, Medical Research Division, National Research Centre, Giza 12622, Egypt.
authors.forename: Hadeer A
authors.initials: HA
authors.lastname: Aglan
keywords: Anti-apoptotic effect; Anti-inflammatory action; Bone marrow derived mesenchymal stem cells; Neurogenic potential; Ovariectomy; Parkinson’s disease; Pathophysiology; Rotenone