Does the mesenchymal stem cell therapy improve the streptozotocin-induced neurodegeneration in rats

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Does the mesenchymal stem cell therapy improve the streptozotocin-induced neurodegeneration in rats
  ADbrain whichmaybe exacerbated by underlying conditions such as diabe-tes.ADtransgenicmousemodelswhichpresentwithAbpathologyshowde-creased memory function and treatment with a novel, patented formulation,zinc plus cyclo(his-pro) (ZC) maybe beneficial in both reducing Ab levelsand increasing memory function. In this study we treated R1.40 transgenicmice with ZC and tested for learning and working memory on a BarnesMaze in correlation with AD specific pathology.  Methods:  Nine to twelvemonth old huAPP-YAC transgenic mice (R1.40 strain) were treated with10 ml/L Zn plus 1.9 mg/L cyclo(his-pro) (ZC) in water ad libitum, with con-trols having no treatmentadded to water. Mice weretested on a BarnesMazefor measurement of learning and working memory deficits for 6 months.Postmortem, brains were harvested and analyzed for AD specific pathology. Results:  This study has shown that the novel formulation ZC alters learningbehavior and AD specific pathology in the R1.40 transgenic mouse model of AD.  Conclusions:  This study is beneficial in the ongoing pursuit of novelformulation for the treatment of Alzheimer’s disease. P3-398 DOESTHEMESENCHYMALSTEMCELLTHERAPYIMPROVE THE STREPTOZOTOCIN-INDUCEDNEURODEGENERATION IN RATS?Ahmet Turan Isik 1 , Turgay Celik 2 , Ali Ugur Ur al 3 , Murat Tosun 4 ,Gokhan Ulusoy 5 , Ergun Bozoglu 6 , Elvin Akdag 7 , Birsen Elibol 8 ,  1 GulhaneSchool of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Ankara, Turkey;  2 Gulhane School of Medicine, Department of  Pharmacology, Ankara, Turkey;  3 Gulhane School of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, Turkey;  4  Afyon Ko-catepe University Medical Faculty Department of Histology Embryology, Afyonkarahisar, Turkey;  5 Gulhane School of Medicine, Department of  Pharmacology, Ankara, Turkey;  6  Gulhane School of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Ankara, Turkey; 7   Department of Pharmacology, Gulhane School of Medicine, Ankara, Tur-key;  8  Department of Biological Science, Middle East Technical University, Ankara, Turkey. Contact e-mail: Background:  The stem cell therapy seems like to have a place in clinicalmanagement of Alzheimer Disease (AD), due to the current therapies for AD isn’t curative and is only a temporary measure. The goal of the current study was investigated the roles of the bone marrow-derived mesenchymalstem cells (BM-MSCs) therapy in the streptozotocin (STZ) induced neuro-degeneration in rats and was examined the engraftment capability of stemcells and effects of BM-MSCs therapy on the cognitive symptoms (water maze tests) in this model.  Methods:  Seventy-five female Wistar ratswere included in the study. 15 Naive rats of 75 were non-operated for con-trol (Group I). While STZ was given to rats via intra-cerebroventricular (ICV) injection for Alzheimer model (STZ Group); artificial CSF wasgiven to the others via ICV for sham group (Group II). After the demon-stration of acquisition impairment, STZ Group was divided as Group III,IV and V. Group II(SHAM+Vh) and III(STZ+Vh) were administered vehi-cle (0.5 ml, IV), Group IV and V(STZ+ BM-MSCs) were received 10 6 BM-MSCs and 10 6 BM-MSCs(twice, once a week), respectively. Follow-ing treatment period after the reevaluation of memory test, all the rats weresacrificed and all the brains were extracted for histopathological examina-tion.  Results:  Significant neuronal loss was shown in the STZ treated rats,when compared with Group I and II (p < 0.001). The prominent improve-ment in the test performance of rats was demonstrated by BM-MSCs ther-apy, although this was not statistically significant. However, BM-MSCswas significantly improved the neuronal loss in rats hippocampus CA1 re-gion in Group V as compared with the Group III (p < 0.001). Furthermore,significant neovascularization was also seen in Group V. Improvements inboth test performance and histopathology of the rats in Group V was better than Group IV (p < 0.01).  Conclusions:  It seems like that BM-MSCs ther-apy might be provided the neuronal replacement in this model. In addition,it was also demonstrated that BM-MSCs therapy might be improved cog-nition in STZ induced neurodegeneration. These improving effects of BM-MSCs therapy should be needed to detail in further studies and give ushope for the future. P3-399 PREDICTING THE CHOLINESTERASES BINDINGSITES FOR PLANT DERIVED INHIBITORS:TEMPLATE TO DESIGN A DRUG FORSYMPTOMATIC TREATMENT OFALZHEIMER’SDISEASEVenkatachalam Lakshmi , Rathanam Boopathy,  Bharathiar University,Coimbatore, India. Contact e-mail: Background:  Central cholinergic system is considered as most important neurotransmitter system involved in regulation of cognitive functions.  Cho-linergicneuronalloss inhippocampalregionismainfeatureofAlzheimer’sdisease (AD) andenhancement of central cholinergicactivity is presentlythemainstayofpharmacotherapyofsenileAlzheimertypeofDementia. Cholin-esteraseinhibitors (ChEIs) are the only drugs so far approved for AD treat-ment. Therapeutically used inhibitors include  natural phytoconstituents and synthetic compounds, synthesized based on template natural phytocon-stituents. Also ChEIs have potential roles in VascularDementia, Parkinson’sDisease and Down Syndrome treatment. Methods: i)  In silico  dockingstudyof plant based inhibitors onto human acetylcholinesterase protein ii)  In silico docking study of plant based inhibitors onto human butyrylcholinesteraseprotein  Results:  i) The docking algorithm,  LigandFit  differentiates activeligands as inhibitors from inactive ones. ii) Of all scoring functions namelyDockScore,LigScore1,LigScore2,Jain,PLPandPMF, DockScore istheef-ficient scoring tool in predicting best binding inhibitor. iii)  Ser203, His447,Arg463,Tyr124,Trp86,Glu202,Phe295,Phe297andTyr337 are the res-idues important in inhibitor binding to hAChE. iv)  Ser198, Glu197, Asp70,Thr120,His438,Trp82,Gly116,Gly115,Phe329andTyr332 residuesareimportant in inhibitor binding to hBChE. Conclusions: The structure of best docked inhibitors can be used as template for designing new, selective andpowerful AD drugs. P3-400 NEURONAL DIFFERENTIATION OFMESENCHYMAL STEM CELLS FROM BONEMARROW OF HUMAN MASTOID PROCESS  IN VITRO Min-KyungSong 1 ,HyongHoCho 2 ,ByungChaeKim 2 ,HanSeongJeong 3 ,Su Jeong Jang 3 ,  1  Kwangju Christian Hospital, Gwangju, Korea;  2 Chonnam National University Hospital, Gwangju, Korea;  3 Chonnam National University Medical School, Gwangju, Korea. Contact e-mail:  Background: Neuraltissue has historicallybeen regardedas havingpoorre-generative capacity but recent advances in the growing fields of tissue engi-neering and regenerative medicine have opened new hopes for thetreatmentofnerveinjuriesandneurodegenerativedisorders.Reportsofneuraldifferentiation of mesenchymal stem cells suggest the possibility that thesecells may serve as a source for stem cell-based regenerative medicine to treat neurological disorders.The purposeof this studywas to generateneural cellsby differentiation of bone marrow-derived mesenchymal stem cells that iso-lated from human mastoid process.  Methods:  Human mesenchymal stemcells (hMSCs) isolated from human mastoid process bone marrow duringmastoidectomyforchronicotitismediasurgerywerecharacterizedusingfluo-rescence-activatedcellsorter.InductionofneuraldifferentiationfromhMSCswasperformedusingmitogenicfactors(basicfibroblastgrowthfactor,epider-mal growth factor, forskolin, isobutylmethylxanthine), and the characteriza-tion of differentiated hMSCs was performed using immunohistochemistry,RT-PCR and whole cell patch clamp technique.  Results:  hMSCs frombone marrow of mastoid process were isolated and cultured. Differentiatedcells from hMSCs expressed mRNA transcripts for neuron specific markers,TUJ1 and neurofilament proteins (NF-L, NF-M) as determined by RT-PCR,and neuron specific markers, suhc as NeuN, TUJ1, microtubule-associatedprotein-2 (MAP2) and glial fibrillary acidic protein by immunohistochemis-try. These cells showed voltage-dependent sodium currents that was blockedby tetrodotoxin.  Conclusions:  hMSCs, which were isolated from humanmastoid process bone marrow, were one of the good sources for stem cell-based regenerative medicine to treat neurological disorders.  Poster Presentations P3  S569
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