TY - JOUR

T1 - The role of T-cells in neurobehavioural development

T2 - Insights from the immunodeficient nude mice

AU - Bauer-Negrini, Guilherme

AU - Deckmann, Iohanna

AU - Schwingel, Gustavo Brum

AU - Hirsch, Mauro Mozael

AU - Fontes-Dutra, Mellanie

AU - Carello-Collar, Giovanna

AU - Halliwell, Diane E

AU - Paraskevaidi, Maria

AU - Morais, Camilo L M

AU - Martin, Francis L

AU - Riesgo, Rudimar

AU - Gottfried, Carmem

AU - Bambini-Junior, Victorio

N1 - Copyright © 2021. Published by Elsevier B.V.

PY - 2022/2/10

Y1 - 2022/2/10

N2 - Mice homozygous for the nude mutation (Foxn1nu) are hairless and exhibit congenital dysgenesis of the thymic epithelium, resulting in a primary immunodeficiency of mature T-cells, and have been used for decades in research with tumour grafts. Early studies have already demonstrated social behaviour impairments and central nervous system (CNS) alterations in these animals, but did not address the complex interplay between CNS, immune system and behavioural alterations. Here we investigate the impact of T-cell immunodeficiency on behaviours relevant to the study of neurodevelopmental and neuropsychiatric disorders. Moreover, we aimed to characterise in a multidisciplinary manner the alterations related to those findings, through evaluation of the excitatory/inhibitory synaptic proteins, cytokines expression and biological spectrum signature of different biomolecules in nude mice CNS. We demonstrate that BALB/c nude mice display sociability impairments, a complex pattern of repetitive behaviours and higher sensitivity to thermal nociception. These animals also have a reduced IFN-γ gene expression in the prefrontal cortex and an absence of T-cells in meningeal tissue, both known modulators of social behaviour. Furthermore, excitatory synaptic protein PSD-95 immunoreactivity was also reduced in the prefrontal cortex, suggesting an intricate involvement of social behaviour related mechanisms. Lastly, employing biospectroscopy analysis, we have demonstrated that BALB/c nude mice have a different CNS spectrochemical signature compared to their heterozygous littermates. Altogether, our results show a comprehensive behavioural analysis of BALB/c nude mice and potential neuroimmunological influences involved with the observed alterations.

AB - Mice homozygous for the nude mutation (Foxn1nu) are hairless and exhibit congenital dysgenesis of the thymic epithelium, resulting in a primary immunodeficiency of mature T-cells, and have been used for decades in research with tumour grafts. Early studies have already demonstrated social behaviour impairments and central nervous system (CNS) alterations in these animals, but did not address the complex interplay between CNS, immune system and behavioural alterations. Here we investigate the impact of T-cell immunodeficiency on behaviours relevant to the study of neurodevelopmental and neuropsychiatric disorders. Moreover, we aimed to characterise in a multidisciplinary manner the alterations related to those findings, through evaluation of the excitatory/inhibitory synaptic proteins, cytokines expression and biological spectrum signature of different biomolecules in nude mice CNS. We demonstrate that BALB/c nude mice display sociability impairments, a complex pattern of repetitive behaviours and higher sensitivity to thermal nociception. These animals also have a reduced IFN-γ gene expression in the prefrontal cortex and an absence of T-cells in meningeal tissue, both known modulators of social behaviour. Furthermore, excitatory synaptic protein PSD-95 immunoreactivity was also reduced in the prefrontal cortex, suggesting an intricate involvement of social behaviour related mechanisms. Lastly, employing biospectroscopy analysis, we have demonstrated that BALB/c nude mice have a different CNS spectrochemical signature compared to their heterozygous littermates. Altogether, our results show a comprehensive behavioural analysis of BALB/c nude mice and potential neuroimmunological influences involved with the observed alterations.

KW - Animals

KW - Mental Disorders/immunology

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Nude

KW - Mutation/genetics

KW - Neurodevelopmental Disorders/immunology

KW - T-Lymphocytes/immunology

U2 - 10.1016/j.bbr.2021.113629

DO - 10.1016/j.bbr.2021.113629

M3 - Journal article

C2 - 34656692

VL - 418

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

M1 - 113629

ER -