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Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Univ, IECNSIR, Univ Hosp, Frodingsgatan 12,Bldg 28, SE-75421 Uppsala, Sweden.;Univ Med & Pharm, Dept Clin Neurosci, Cluj Napoca, Romania.;Univ Basque Country, Dept Neurosci, Bilbao, Spain..
Univ Med & Pharm, Dept Clin Neurosci, Cluj Napoca, Romania.;RoNeuro Inst Neurol Res & Diagnost, 37 Mircea Eliade St, Cluj Napoca 400364, Romania..
Univ Basque Country, Dept Neurosci, Bilbao, Spain.;BioCruces Hlth Res Inst, Nanoneurosurg Grp, Baracaldo 48903, Bizkaia, Spain.;Univ Autonoma Chile, Fac Hlth Sci, Santiago, Chile..
Banaras Hindu Univ, Dept Biomat, Sch Biomed Engn, Indian Inst Technol, Varanasi, Uttar Pradesh, India..
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 300-311Article in journal (Refereed) Published
Abstract [en]

Neprilysin (NPL), the rate-limiting enzyme for amyloid beta peptide (A beta P), appears to play a crucial role in the pathogenesis of Alzheimer's disease (AD). Since mesenchymal stem cells (MSCs) and/or cerebrolysin (CBL, a combination of neurotrophic factors and active peptide fragments) have neuroprotective effects in various CNS disorders, we examined nanowired delivery of MSCs and CBL on NPL content and brain pathology in AD using a rat model. AD-like symptoms were produced by intraventricular (i.c.v.) administration of A beta P (1-40) in the left lateral ventricle (250 ng/10 mu l, once daily) for 4 weeks. After 30 days, the rats were examined for NPL and A beta P concentrations in the brain and related pathology. Co-administration of TiO2-nanowired MSCs (10(6) cells) with 2.5 ml/kg CBL (i.v.) once daily for 1 week after 2 weeks of A beta P infusion significantly increased the NPL in the hippocampus (400 pg/g) from the untreated control group (120 pg/g; control 420 +/- 8 pg/g brain) along with a significant decrease in the A beta P deposition (45 pg/g from untreated control 75 pg/g; saline control 40 +/- 4 pg/g). Interestingly, these changes were much less evident when the MSCs or CBL treatment was given alone. Neuronal damages, gliosis, and myelin vesiculation were also markedly reduced by the combined treatment of TiO2, MSCs, and CBL in AD. These observations are the first to show that co-administration of TiO2-nanowired CBL and MSCs has superior neuroprotective effects in AD probably due to increasing the brain NPL level effectively, not reported earlier.

Place, publisher, year, edition, pages
Humana Press, 2018. Vol. 55, no 1, p. 300-311
Keywords [en]
Alzheimer's disease (AD), Neprilysin (NPL), Amyloid-beta peptide (a beta P), Mesenchymal stem cells (MSCs), Cerebrolysin (CBL), TiO2 nanowires, Nanodelivery
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-346902DOI: 10.1007/s12035-017-0742-9ISI: 000424702600030PubMedID: 28844104OAI: oai:DiVA.org:uu-346902DiVA, id: diva2:1195153
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved

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Sharma, Hari ShankerSharma, Aruna

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