Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia

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dc.contributor.author Hadar, R.
dc.contributor.author Bikovski, L.
dc.contributor.author Soto Montenegro, Mª Luisa
dc.contributor.author Schimke, J.
dc.contributor.author Maier, P.
dc.contributor.author Ewing, S.
dc.contributor.author Voget, M.
dc.contributor.author Wieske, Franziska
dc.contributor.author Goetz, T.
dc.contributor.author Desco Menéndez, Manuel
dc.contributor.author Hamani, Clement
dc.contributor.author Pascau González-Garzón, Javier
dc.contributor.author Weiner, Ina
dc.contributor.author Winter, Christine
dc.date.accessioned 2021-06-21T10:37:28Z
dc.date.available 2021-06-21T10:37:28Z
dc.date.issued 2017-04-04
dc.identifier.bibliographicCitation Molecular Psychiatry (2018) 23(4), 943–951.
dc.identifier.issn 1359-4184
dc.identifier.uri http://hdl.handle.net/10016/32900
dc.description.abstract The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia’s neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.
dc.description.sponsorship We thank Renate Winter, Doris Zschaber and Roselies Pickert for excellent technical assistance. This research was conducted under the EraNet Neuron framework (DBS_F20rat) and supported by the BMBF, Germany (B01EW1103, 01EE1403A), Fundación Mapfre, Comunidad de Madrid and the Ministry of Economy and Competitiveness ISCIII-FIS grants (PI14/00860, CPII/00005) co-financed by ERDF (FEDER) Funds from the European Commission, ‘A way of making Europe’, Spain (PI14/00860, CPII/00005, MV1500002), the CSO-MOH, Israel (3-8580) and the Canadian Institutes of Health Research, Canada (CIHR, 110068), and co-financed by the DFG, Germany (WI 2140/1-1/2; WI 2140/2-1).
dc.format.extent 8
dc.language.iso eng
dc.publisher Springer Nature
dc.rights © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1359-4184/18
dc.subject.other Deep brain stimulation
dc.subject.other Animal disease models
dc.subject.other Psychotic disorders
dc.subject.other Schizophrenia
dc.subject.other Neurotransmitter agents
dc.subject.other Sensory gating
dc.subject.other Dopamine
dc.subject.other Brain
dc.subject.other Neuroscience
dc.title Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia
dc.type article
dc.description.status Publicado
dc.subject.eciencia Biología y Biomedicina
dc.subject.eciencia Medicina
dc.identifier.doi https://doi.org/10.1038/mp.2017.52
dc.rights.accessRights openAccess
dc.relation.projectID Gobierno de España. PI14/00860
dc.relation.projectID Gobierno de España. CPII/00005
dc.type.version acceptedVersion
dc.identifier.publicationfirstpage 943
dc.identifier.publicationissue 4
dc.identifier.publicationlastpage 951
dc.identifier.publicationtitle MOLECULAR PSYCHIATRY
dc.identifier.publicationvolume 23
dc.identifier.uxxi AR/0000021234
dc.affiliation.dpto UC3M. Departamento de Bioingeniería
dc.affiliation.grupoinv UC3M. Grupo de Investigación: Biomedical Imaging and Instrumentation Group
dc.affiliation.grupoinv UC3M. Grupo de Investigación: BSEL - Laboratorio de Ciencia e Ingeniería Biomédica
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