Nanodelivery of Cerebrolysin and Rearing in Enriched Environment Induce Neuroprotective Effects in a Preclinical Rat Model of Parkinson's Disease
Autor: | Luisa Ugedo, Asya Ozkizilcik, Aruna Sharma, José Vicente Lafuente, José Ángel Ruiz-Ortega, Hari Shanker Sharma, Hodei Cepeda, Herbert Moessler, Catalina Requejo, Ryan Tian |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Parkinson's disease Neuroscience (miscellaneous) Striatum Pharmacology Environment Neuroprotection Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Drug Delivery Systems Parkinsonian Disorders Dopamine hemic and lymphatic diseases medicine Animals Amino Acids Protein kinase B Environmental enrichment Tyrosine hydroxylase business.industry medicine.disease Rats Disease Models Animal 030104 developmental biology Neuroprotective Agents Neurology chemistry Cerebrolysin Immunology Nanoparticles business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Molecular neurobiology. 55(1) |
ISSN: | 1559-1182 |
Popis: | 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. |
Databáze: | OpenAIRE |
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