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Nanodelivery of Cerebrolysin and Rearing in Enriched Environment Induce Neuroprotective Effects in a Preclinical Rat Model of Parkinson's Disease
Univ Basque Country UPV EHU, Dept Neurosci, LaNCE, Leioa, Vizcaya, Spain..
Univ Basque Country UPV EHU, Dept Pharmacol, Leioa, Vizcaya, Spain..
Univ Basque Country UPV EHU, Dept Neurosci, LaNCE, Leioa, Vizcaya, Spain..
Uppsala Univ, Int Expt CNS Injury & Repair, Uppsala, Sweden..
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 286-299Article in journal (Refereed) Published
Abstract [en]

Rearing in enriched environment (EE) improves the recuperation in animal models of Parkinson's disease (PD). Administration of TiO2-nanowired cerebrolysin (CBL) could represent an additional strategy to protect or repair the nigrostriatal system. This study aims to explore morphofunctional and biochemical changes in a preclinical stage of PD testing the synergistic efficiency of combining both strategies, housing in EE, and nanodelivery of CBL. Sprague-Dawley male rats receiving intrastriatally 6-hydroxydopamine after a short evolution time were segregated into CBL group (rats receiving nanowired CBL), EE group (rats housed in EE), CBL + EE group (rats housed in EE and receiving nanowired CBL), and control group (rats without additional treatment). Prodromic stage and treatment effects were characterized by the presence of motor symptoms (amphetamine-induced rotational behavior test). Tyrosine hydroxylase (TH) immunohistochemistry and Western blot (p-Akt/Akt and p-ERK/ERK 1/2 as survival markers and caspase-3 as apoptotic marker) were performed in striatum and SN. A decrease in motor symptoms was shown by rats receiving CBL. EE monitoring cages revealed that rats from CBL + EE group showed more significant number of laps in the wheel than EE group. In SN, CBL + EE group also presented the highest neuronal density. Moreover, p-Akt/Akt and p-ERK/ERK 1/2 ratio was significant higher and caspase-3 expression was lower in CBL + EE group. In conclusion, the combination of CBL and EE provided evidence of neuoprotective-neurorestorative mechanisms by which this combined strategy promoted morphofunctional improvement by activation of survival pathways after dopamine depletion in a preclinical model of PD.

Place, publisher, year, edition, pages
Humana Press, 2018. Vol. 55, no 1, p. 286-299
Keywords [en]
Parkinson'sdisease, 6-OHDA, Preclinical stage, Nanowired cerebrolysin, Enriched environment, Neuroprotection
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-346901DOI: 10.1007/s12035-017-0741-xISI: 000424702600029PubMedID: 28840482OAI: oai:DiVA.org:uu-346901DiVA, id: diva2:1195176
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved

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Sharma, H.S.

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