Sex-dependent role of CD300f immune receptor in generalized anxiety disorder
Generalized Anxiety Disorder (GAD) presents a high prevalence in the population, leading to distress and disability. Immune system alterations have been associated with anxiety-related behaviors in rodents and GAD patients. CD300f immune receptors are highly expressed in microglia and participate no...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-02-01
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| Series: | Brain, Behavior, & Immunity - Health |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354620301563 |
| _version_ | 1831559382178988032 |
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| author | Fernanda N. Kaufmann Natalia Lago Daniela Alí-Ruiz Karen Jansen Luciano D.M. Souza Ricardo A. Silva Diogo R. Lara Gabriele Ghisleni Hugo Peluffo Manuella P. Kaster |
| author_facet | Fernanda N. Kaufmann Natalia Lago Daniela Alí-Ruiz Karen Jansen Luciano D.M. Souza Ricardo A. Silva Diogo R. Lara Gabriele Ghisleni Hugo Peluffo Manuella P. Kaster |
| author_sort | Fernanda N. Kaufmann |
| collection | DOAJ |
| description | Generalized Anxiety Disorder (GAD) presents a high prevalence in the population, leading to distress and disability. Immune system alterations have been associated with anxiety-related behaviors in rodents and GAD patients. CD300f immune receptors are highly expressed in microglia and participate not only in the modulation of immune responses but also in pruning and reshaping synapses. It was recently demonstrated that CD300f might be influential in the pathogenesis of depression in a sex-dependent manner. Here, we evaluated the role of CD300f immune receptor in anxiety, using CD300f knockout mice (CD300f−/−) and patients with GAD. We observed that male CD300f−/− mice had numerous behavioral changes associated with a low-anxiety phenotype, including increased open field central locomotion and rearing behaviors, more exploration in the open arms of the elevated plus-maze test, and decreased latency to eat in the novelty suppressed feeding test. In a cross-sectional population-based study, including 1111 subjects, we evaluated a common single-nucleotide polymorphism rs2034310 (C/T) in the cytoplasmatic tail of CD300f gene in individuals with GAD. Notably, we observed that the T allele of the rs2034310 polymorphism conferred protection against GAD in men, even after adjusting for confounding variables. Overall, our data demonstrate that CD300f immune receptors are involved in the modulation of pathological anxiety behaviors in a sex-dependent manner. The biological basis of these sex differences is still poorly understood, but it may provide significant clues regarding the neuropathophysiological mechanisms of GAD and can pave the way for future specific pharmacological interventions. |
| first_indexed | 2024-12-17T05:27:11Z |
| format | Article |
| id | doaj.art-3f2975e20a2241058699e53d2666105e |
| institution | Directory Open Access Journal |
| issn | 2666-3546 |
| language | English |
| last_indexed | 2024-12-17T05:27:11Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj.art-3f2975e20a2241058699e53d2666105e2022-12-21T22:01:49ZengElsevierBrain, Behavior, & Immunity - Health2666-35462021-02-0111100191Sex-dependent role of CD300f immune receptor in generalized anxiety disorderFernanda N. Kaufmann0Natalia Lago1Daniela Alí-Ruiz2Karen Jansen3Luciano D.M. Souza4Ricardo A. Silva5Diogo R. Lara6Gabriele Ghisleni7Hugo Peluffo8Manuella P. Kaster9Department of Psychiatry and Neuroscience, Faculty of Medicine and CERVO Brain Research Center, Université Laval, Quebec City, CanadaNeuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, UruguayNeuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, UruguayDepartment of Life and Health Sciences, Catholic University of Pelotas, Rio Grande do Sul, BrazilDepartment of Life and Health Sciences, Catholic University of Pelotas, Rio Grande do Sul, BrazilDepartment of Life and Health Sciences, Catholic University of Pelotas, Rio Grande do Sul, BrazilDepartment of Cellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, BrazilDepartment of Life and Health Sciences, Catholic University of Pelotas, Rio Grande do Sul, BrazilNeuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, UruguayDepartment of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil; Corresponding author.Generalized Anxiety Disorder (GAD) presents a high prevalence in the population, leading to distress and disability. Immune system alterations have been associated with anxiety-related behaviors in rodents and GAD patients. CD300f immune receptors are highly expressed in microglia and participate not only in the modulation of immune responses but also in pruning and reshaping synapses. It was recently demonstrated that CD300f might be influential in the pathogenesis of depression in a sex-dependent manner. Here, we evaluated the role of CD300f immune receptor in anxiety, using CD300f knockout mice (CD300f−/−) and patients with GAD. We observed that male CD300f−/− mice had numerous behavioral changes associated with a low-anxiety phenotype, including increased open field central locomotion and rearing behaviors, more exploration in the open arms of the elevated plus-maze test, and decreased latency to eat in the novelty suppressed feeding test. In a cross-sectional population-based study, including 1111 subjects, we evaluated a common single-nucleotide polymorphism rs2034310 (C/T) in the cytoplasmatic tail of CD300f gene in individuals with GAD. Notably, we observed that the T allele of the rs2034310 polymorphism conferred protection against GAD in men, even after adjusting for confounding variables. Overall, our data demonstrate that CD300f immune receptors are involved in the modulation of pathological anxiety behaviors in a sex-dependent manner. The biological basis of these sex differences is still poorly understood, but it may provide significant clues regarding the neuropathophysiological mechanisms of GAD and can pave the way for future specific pharmacological interventions.http://www.sciencedirect.com/science/article/pii/S2666354620301563Generalized anxiety disorderImmune systemCD300f receptorsPolymorphism |
| spellingShingle | Fernanda N. Kaufmann Natalia Lago Daniela Alí-Ruiz Karen Jansen Luciano D.M. Souza Ricardo A. Silva Diogo R. Lara Gabriele Ghisleni Hugo Peluffo Manuella P. Kaster Sex-dependent role of CD300f immune receptor in generalized anxiety disorder Brain, Behavior, & Immunity - Health Generalized anxiety disorder Immune system CD300f receptors Polymorphism |
| title | Sex-dependent role of CD300f immune receptor in generalized anxiety disorder |
| title_full | Sex-dependent role of CD300f immune receptor in generalized anxiety disorder |
| title_fullStr | Sex-dependent role of CD300f immune receptor in generalized anxiety disorder |
| title_full_unstemmed | Sex-dependent role of CD300f immune receptor in generalized anxiety disorder |
| title_short | Sex-dependent role of CD300f immune receptor in generalized anxiety disorder |
| title_sort | sex dependent role of cd300f immune receptor in generalized anxiety disorder |
| topic | Generalized anxiety disorder Immune system CD300f receptors Polymorphism |
| url | http://www.sciencedirect.com/science/article/pii/S2666354620301563 |
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