Maternal Immune Activation Induces Cortical Catecholaminergic Hypofunction and Cognitive Impairments in Offspring
dc.contributor.author | Pérez Palomar, Blanca | |
dc.contributor.author | Erdozáin Fernández, Amaia Maite | |
dc.contributor.author | Erkizia Santamaría, Inés | |
dc.contributor.author | Ortega Calvo, Jorge | |
dc.contributor.author | Meana Martínez, José Javier ![]() | |
dc.date.accessioned | 2024-05-07T16:43:42Z | |
dc.date.available | 2024-05-07T16:43:42Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Journal of Neuroimmune Pharmacology 18 : 348-365 (2023) | es_ES |
dc.identifier.issn | 1557-1890 | |
dc.identifier.issn | 1557-1904 | |
dc.identifier.uri | http://hdl.handle.net/10810/67656 | |
dc.description.abstract | Background Impairment of specific cognitive domains in schizophrenia has been associated with prefrontal cortex (PFC) catecholaminergic deficits. Among other factors, prenatal exposure to infections represents an environmental risk factor for schizophrenia development in adulthood. However, it remains largely unknown whether the prenatal infection-induced changes in the brain may be associated with concrete switches in a particular neurochemical circuit, and therefore, if they could alter behavioral functions. Methods In vitro and in vivo neurochemical evaluation of the PFC catecholaminergic systems was performed in offspring from mice undergoing maternal immune activation (MIA). The cognitive status was also evaluated. Prenatal viral infection was mimicked by polyriboinosinic-polyribocytidylic acid (poly(I:C)) administration to pregnant dams (7.5 mg/kg i.p., gestational day 9.5) and consequences were evaluated in adult offspring. Results MIA-treated offspring showed disrupted recognition memory in the novel object recognition task (t = 2.30, p = 0.031). This poly(I:C)-based group displayed decreased extracellular dopamine (DA) concentrations compared to controls (t = 3.17, p = 0.0068). Potassium-evoked release of DA and noradrenaline (NA) were impaired in the poly(I:C) group (DA: Ft[10,90] = 43.33, p < 0.0001; Ftr[1,90] = 1.224, p = 0.2972; Fi[10,90] = 5.916, p < 0.0001; n = 11); (NA: Ft[10,90] = 36.27, p < 0.0001; Ftr[1,90] = 1.841, p = 0.208; Fi[10,90] = 8.686, p < 0.0001; n = 11). In the same way, amphetamine‐evoked release of DA and NA were also impaired in the poly(I:C) group (DA: Ft[8,328] = 22.01, p < 0.0001; Ftr[1,328] = 4.507, p = 0.040; Fi[8,328] = 2.319, p = 0.020; n = 43); (NA: Ft[8,328] = 52.07; p < 0.0001; Ftr[1,328] = 4.322; p = 0.044; Fi[8,398] = 5.727; p < 0.0001; n = 43). This catecholamine imbalance was accompanied by increased dopamine D1 and D2 receptor expression (t = 2.64, p = 0.011 and t = 3.55, p = 0.0009; respectively), whereas tyrosine hydroxylase, DA and NA tissue content, DA and NA transporter (DAT/NET) expression and function were unaltered. Conclusions MIA induces in offspring a presynaptic catecholaminergic hypofunction in PFC with cognitive impairment. This poly(I:C)-based model reproduces catecholamine phenotypes reported in schizophrenia and represents an opportunity for the study of cognitive impairment associated to this disorder. | es_ES |
dc.description.sponsorship | Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by Grants SAF2013-48586-R; RTI2018-094414-A-I00 and PID2021–123508OB-I00, funded by MCIN/AEI/https://doi.org/10.13039/501100011033, by ERDF A way of making Europe and by the Basque Government (IT-1211-19; IT1512-22). BP-P received a predoctoral fellowship from the Spanish MECD. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer Nature | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2013-48586-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-094414-A-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2021–123508OB-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | maternal immune activation | es_ES |
dc.subject | microdialysis | es_ES |
dc.subject | dopamine | es_ES |
dc.subject | noradrenaline | es_ES |
dc.subject | D1 receptors | es_ES |
dc.subject | D2 receptors | es_ES |
dc.subject | cognitive impairment | es_ES |
dc.title | Maternal Immune Activation Induces Cortical Catecholaminergic Hypofunction and Cognitive Impairments in Offspring | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://link.springer.com/article/10.1007/s11481-023-10070-1 | es_ES |
dc.identifier.doi | 10.1007/s11481-023-10070-1 | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
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