RT Journal Article
T1 Differential regulation of innate immune system in frontal cortex and hippocampus in a “double-hit” neurodevelopmental model in rats
A1 González Bris, Álvaro
A1 Mac-Dowell Mata, Karina Soledad
A1 Martín Hernández, David
A1 Moreno Moreno, Beatriz
A1 Muñoz Madrigal, José Luis
A1 García Bueno, Borja
A1 Caso Fernández, Javier Rubén
A1 Leza Cerro, Juan Carlos
AB Neurodevelopmental disorders (NDs) are neuropsychiatric conditions affecting central nervous system development, characterized by cognitive and behavioural alterations. Inflammation has been recently linked to NDs. Animal models are essential for understanding their pathophysiology and identifying therapeutic targets. Double-hit models can reproduce neurodevelopmental and neuroinflammatory impairments.Sixty-seven newborn rats were assigned to four groups: Control, Maternal deprivation (MD, 24-h-deprivation), Isolation (Iso, 5 weeks), and Maternal deprivation ​+ ​Isolation (MD ​+ ​Iso, also known as double-hit). Cognitive dysfunction was assessed using behavioural tests. Inflammasome, MAPKs, and TLRs inflammatory elements expression in the frontal cortex (FC) and hippocampus (HP) was analysed through western blot and qRT-PCR. Oxidative/nitrosative (O/N) evaluation and corticosterone levels were measured in plasma samples.Double-hit group was affected in executive and working memory. Most inflammasomes and TLRs inflammatory responses were increased in FC compared to the control group, whilst MAPKs were downregulated. Conversely, hippocampal inflammasome and inflammatory components were reduced after the double-hit exposure, while MAPKs were elevated.Our findings reveal differential regulation of innate immune system components in FC and HP in the double-hit group. Further investigations on MAPKs are necessary to understand their role in regulating HP neuroinflammatory status, potentially linking our MAPKs results to cognitive impairments through their proliferative and anti-inflammatory activity.
PB Elsevier
SN 1933-7213
YR 2023
FD 2023-10-28
LK https://hdl.handle.net/20.500.14352/110048
UL https://hdl.handle.net/20.500.14352/110048
LA eng
NO Álvaro G. Bris, Karina S. MacDowell, Cristina Ulecia-Morón, David Martín-Hernández, Beatriz Moreno, José L.M. Madrigal, Borja García-Bueno, Javier R. Caso, Juan C. Leza, Differential regulation of innate immune system in frontal cortex and hippocampus in a “double-hit” neurodevelopmental model in rats, Neurotherapeutics, Volume 21, Issue 1, 2024, e00300, ISSN 1878-7479, https://doi.org/10.1016/j.neurot.2023.10.010.
NO Ministerio de Economía, Industria y Competitividad (España)
NO Ministerio de Ciencia e Innovación (España)
NO Instituto de Salud Carlos III (España)
NO Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)
DS Docta Complutense
RD 21 abr 2025