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Silvertown J.D.,Ontario Cancer Institute | Neschadim A.,University of Toronto | Liu H.-N.,Center for Research in Neurodegenerative Diseases | Walia J.S.,Ontario Cancer Institute | And 5 more authors.
Regulatory Peptides | Year: 2010

Evidence suggests that relaxin-3 may have biological functions in the reproductive and central nervous systems. To date, however, relaxin-3 biodistribution has only been investigated in the mouse, rat, pig and teleost fish. Characterizing relaxin-3 gene structure, expression patterns, and function in non-human primates and humans is critical to delineating its biological significance. Experiments were performed to clone the rhesus macaque orthologues of the relaxin-3 peptide hormone and its cognitive receptors (RXFP1 and RXFP4). An investigation of rhesus relaxin-3 bioactivity and RXFP1 binding properties was also performed. Next we sought to investigate relaxin-3 immunoreactivity in human and rhesus macaque tissues. Immunohistofluorescence staining for relaxin-3 in the brain, testis, and prostate indicated predominant immunostaining in the ventral and dorsal tegmental nuclei, interstitial space surrounding the seminiferous tubules, and prostatic stromal cells, respectively. Further, in studies designed towards exploring biological functions, we observed neuroprotective actions of rhesus relaxin-3 on human neuronal cell cultures. Taken together, this study broadens the significance of relaxin-3 as a peptide involved in both neuronal cell function and reproductive tissues in primates. © 2009 Elsevier B.V. All rights reserved. Source

Cerri S.,Center for Research in Neurodegenerative Diseases | Greco R.,National Neurological Institute | Levandis G.,Center for Research in Neurodegenerative Diseases | Ghezzi C.,Center for Research in Neurodegenerative Diseases | And 6 more authors.
Stem Cells Translational Medicine | Year: 2015

Mesenchymal stemcells (MSCs) have been proposed as a potential therapeutic tool for Parkinson’s disease (PD) and systemic administration of these cells has been tested in preclinical and clinical studies. However, no information on survival and actual capacity of MSCs to reach the brain has been provided. In this study,weevaluatedhoming of intraarterially infused ratMSCs (rMSCs) in thebrain of rats bearing a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal tract, to establishwhether the toxininduced damage is sufficient to grant MSC passage across the blood-brain barrier (BBB) or if a transient BBBdisruptionisnecessary.The rMSCdistributioninperipheralorgans and theeffects of cell infusionon neurodegenerative process andmotor deficitswere also investigated. rMSCswere infused 14 days after 6-OHDA injection. A hyperosmolar solution of mannitol was used to transiently permeabilize the BBB. Behavioralimpairmentwas assessedbyadjusting steptestandresponsetoapomorphine.Animalswere sacrificed 7 and 28 days after cell infusion. Our work shows that appreciable delivery of rMSCs to the brainof6-OHDA-lesionedanimalscanbeobtainedonlyaftermannitol pretreatment.Anotablepercentage of infused cells accumulated in peripheral organs. Infusion of rMSCs did notmodify the progression of 6-OHDA-induced damage or themotor impairment at the stepping test, but induced progressive normalization of the pathological response (contralateral turning) to apomorphine administration. These findings suggest thatmany aspects should be further investigated before considering any translation of MSC systemic administration into the clinical setting for PD treatment. © AlphaMed Press. Source

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