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Author Notes:
R. Barzilay, Laboratory of Neuroscience, Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Sackler Faculty of Medicine, Tel Aviv University, Petach Tikva 49100, Israel. E-mail: barzilyr@post.tau.ac.il
The authors declare no conflict of interest.
Subject:
Research Funding:
This research was supported by the National Institute for Psychobiology in Israel.
Keywords:
- Science & Technology
- Life Sciences & Biomedicine
- Psychiatry
- animal model
- BDNF
- phencyclidine
- schizophrenia
- social behavior
- stem cells
- PREFRONTAL CORTEX
- ANIMAL-MODELS
- PSYCHIATRIC-DISORDERS
- PARKINSONS-DISEASE
- NEURAL PROTEINS
- SCHIZOPHRENIA
- NEUROPROTECTION
- DYSFUNCTION
- DEPRESSION
Intracerebral adult stem cells transplantation increases brain-derived neurotrophic factor levels and protects against phencyclidine-induced social deficit in mice
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Abstract:
Stem cell-based regenerative therapy is considered a promising cellular therapeutic approach for the patients with incurable brain diseases. Mesenchymal stem cells (MSCs) represent an attractive cell source for regenerative medicine strategies for the treatment of the diseased brain. Previous studies have shown that these cells improve behavioral deficits in animal models of neurological disorders such as Parkinson's and Huntington's diseases. In the current study, we examined the capability of intracerebral human MSCs transplantation (medial pre-frontal cortex) to prevent the social impairment displayed by mice after withdrawal from daily phencyclidine (PCP) administration (10 mg kg -1 daily for 14 days). Our results show that MSCs transplantation significantly prevented the PCP-induced social deficit, as assessed by the social preference test. In contrast, the PCP-induced social impairment was not modified by daily clozapine treatment. Tissue analysis revealed that the human MSCs survived in the mouse brain throughout the course of the experiment (23 days). Significantly increased cortical brain-derived neurotrophic factor levels were observed in the MSCs-treated group as compared with sham-operated controls. Furthermore, western blot analysis revealed that the ratio of phosphorylated Akt to Akt was significantly elevated in the MSCs-treated mice compared with the sham controls. Our results demonstrate that intracerebral transplantation of MSCs is beneficial in attenuating the social deficits induced by sub-chronic PCP administration. We suggest a novel therapeutic approach for the treatment of schizophrenia-like negative symptoms in animal models of the disorder.
Copyright information:
© 2011 Macmillan Publishers Limited All rights reserved.
This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).
