TY - JOUR
T1 - Mesenchymal stem cells protect from sub-chronic phencyclidine insult in vivo and counteract changes in astrocyte gene expression in vitro
AU - Barzilay, Ran
AU - Ganz, Javier
AU - Sadan, Ofer
AU - Ben-Zur, Tali
AU - Bren, Ziv
AU - Hinden, Noa
AU - Taler, Michal
AU - Lev, Nirit
AU - Gil-Ad, Irit
AU - Weizman, Abraham
AU - Offen, Daniel
N1 - Funding Information:
Funding for this study was provided by unrestricted grants supplied to the Nueroscience and the Biological psychiatry labs at the Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University. Additionally, specific funding was provided by the National Institute of Psychobiology in Israel (NIPI). Neither Tel Aviv University nor the NIPI played a further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
Funding Information:
This work was supported in part by the National Institute of Psychobiology in Israel , Grant no. 0601564281 .
PY - 2013/9
Y1 - 2013/9
N2 - Mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine strategies in brain diseases. Experimental studies have shown that repeated administration of phencyclidine (PCP) leads to schizophrenia-like behavioral changes in mice. The aim of the present study was to explore the effectiveness of MSC transplantation into the hippocampus in attenuating PCP-induced social behavior deficits. PCP was administered subcutaneously to C57bl mice (10. mg/kg daily) for 2 weeks. On the first day of PCP administration, adult human MSCs were transplanted into the hippocampus. A week after the last PCP dose, the mice underwent social preference testing. MSC transplantation was associated with a significant reduction in the adverse social behavior induced by PCP. Immunohistochemical analysis revealed that the stem cells survived in the mouse brain, and hippocampal Western blot analysis revealed a statistical trend towards a decrease in cleaved caspase 3 protein levels in the stem cell treated group. Upon in vitro co-culture of astrocytes and MSCs, the MSCs, in the presence of PCP, positively regulated astrocyte expression of genes involved in glutamate metabolism and antioxidant defenses. These findings suggest that MSC transplantation into the hippocampus may serve as a novel neuroprotective tool for the treatment of the PCP-induced schizophrenia-like social endophenotype. The mechanism underlying the beneficial behavioral effect may involve modulation of host astrocyte functioning, including glutamate processing and antioxidant capacity.
AB - Mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine strategies in brain diseases. Experimental studies have shown that repeated administration of phencyclidine (PCP) leads to schizophrenia-like behavioral changes in mice. The aim of the present study was to explore the effectiveness of MSC transplantation into the hippocampus in attenuating PCP-induced social behavior deficits. PCP was administered subcutaneously to C57bl mice (10. mg/kg daily) for 2 weeks. On the first day of PCP administration, adult human MSCs were transplanted into the hippocampus. A week after the last PCP dose, the mice underwent social preference testing. MSC transplantation was associated with a significant reduction in the adverse social behavior induced by PCP. Immunohistochemical analysis revealed that the stem cells survived in the mouse brain, and hippocampal Western blot analysis revealed a statistical trend towards a decrease in cleaved caspase 3 protein levels in the stem cell treated group. Upon in vitro co-culture of astrocytes and MSCs, the MSCs, in the presence of PCP, positively regulated astrocyte expression of genes involved in glutamate metabolism and antioxidant defenses. These findings suggest that MSC transplantation into the hippocampus may serve as a novel neuroprotective tool for the treatment of the PCP-induced schizophrenia-like social endophenotype. The mechanism underlying the beneficial behavioral effect may involve modulation of host astrocyte functioning, including glutamate processing and antioxidant capacity.
KW - Animal model
KW - Phencyclidine
KW - Regenerative medicine
KW - Schizophrenia
KW - Social behavior
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=84884208147&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2012.10.002
DO - 10.1016/j.euroneuro.2012.10.002
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C2 - 23116946
AN - SCOPUS:84884208147
SN - 0924-977X
VL - 23
SP - 1115
EP - 1123
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 9
ER -