| Autor: |
Donegan JJ; Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, TX, USA., Tyson JA; Department of Psychiatry, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, USA., Branch SY; Department of Physiology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, TX, USA., Beckstead MJ; Department of Physiology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, TX, USA., Anderson SA; Department of Psychiatry, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, USA., Lodge DJ; Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, TX, USA. |
| Abstrakt: |
An increasing literature suggests that schizophrenia is associated with a reduction in hippocampal interneuron function. Thus, we posit that stem cell-derived interneuron transplants may be an effective therapeutic strategy to reduce hippocampal hyperactivity and attenuate behavioral deficits in schizophrenia. Here we used a dual-reporter embryonic stem cell line to generate enriched populations of parvalbumin (PV)- or somatostatin (SST)-positive interneurons, which were transplanted into the ventral hippocampus of the methylazoxymethanol rodent model of schizophrenia. These interneuron transplants integrate within the existing circuitry, reduce hippocampal hyperactivity and normalize aberrant dopamine neuron activity. Further, interneuron transplants alleviate behaviors that model negative and cognitive symptoms, including deficits in social interaction and cognitive inflexibility. Interestingly, PV- and SST-enriched transplants produced differential effects on behavior, with PV-enriched populations effectively normalizing all the behaviors examined. These data suggest that the stem cell-derived interneuron transplants may represent a novel therapeutic strategy for schizophrenia. |
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