CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness
Posted by Ernesto on Tuesday, 3 June 2025
Autores:
Natalia Lago 1 , Fernanda N Kaufmann 2 , María Luciana Negro-Demontel 1 3 , Daniela Alí-Ruiz 1 , Gabriele Ghisleni 4 , Natalia Rego 5 , Andrea Arcas-García 6 , Nathalia Vitureira 1 7 , Karen Jansen 4 , Luciano M Souza 4 , Ricardo A Silva 4 , Diogo R Lara 8 , Bruno Pannunzio 1 3 , Juan Andrés Abin-Carriquiry 9 , Jesús Amo-Aparicio 10 , Celia Martin-Otal 6 , Hugo Naya 6 , Dorian B McGavern 11 , Joan Sayós 6 , Rubèn López-Vales 10 , Manuella P Kaster 2 , Hugo Peluffo 12 3
Revista (o libro):
Proc Natl Acad Sci U S A
Año:
2020
Mes-dia:
0324
issue, vol, paginas, etc:
117(12):6651-6662
doi:
10.1073/pnas.1911816117
PMID:
32152116
Abstract:
A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. We explored preclinical and clinical evidence for the role of the CD300f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD. We found that a prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) of the human CD300f receptor cytoplasmic tail inhibits the protein kinase C phosphorylation of a threonine and is associated with protection against MDD, mainly in women. Interestingly, CD300f-/- mice displayed several characteristic MDD traits such as augmented microglial numbers, increased interleukin 6 and interleukin 1 receptor antagonist messenger RNA, alterations in synaptic strength, and noradrenaline-dependent and persistent depressive-like and anhedonic behaviors in females. This behavioral phenotype could be potentiated inducing the lipopolysaccharide depression model. RNA sequencing and biochemical studies revealed an association with impaired microglial metabolic fitness. In conclusion, we report a clear association that links the function of the CD300f immune receptor with MDD in humans, depressive-like and anhedonic behaviors in female mice, and altered microglial metabolic reprogramming.
Afiliaciones:
1 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, 11400 Montevideo, Uruguay.
2 Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, 88040-900 Santa Catarina, Brazil.
3 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, 11200 Montevideo, Uruguay.
4 Department of Life and Health Sciences, Catholic University of Pelotas, 96015-560 Rio Grande do Sul, Brazil.
5 Bioinformatics Unit, Institut Pasteur de Montevideo, 11400 Montevideo, Uruguay.
6 Immune Regulation and Immunotherapy Group, CIBBIM-Nanomedicine, Vall d'Hebrón Institut de Recerca, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
7 Department of Physiology, Facultad de Medicina, Universidad de la República, 11200 Montevideo, Uruguay.
8 Department of Cellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul, 90619-900 Porto Alegre, Brazil.
9 Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, Uruguay.
10 Departament de Biologia Cel·lular, Fisiologia i Immunologia, Institut de Neurociències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
11 Viral Immunology and Intravital Imaging Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
12 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, 11400 Montevideo, Uruguay; hugo.peluffo@pasteur.edu.uy.
Enlace pubmed:
https://pubmed.ncbi.nlm.nih.gov/32152116/
Enlace full text:
https://www.pnas.org/doi/full/10.1073/pnas.1911816117
Cita:
Lago N, Kaufmann FN, Negro-Demontel ML, Alí-Ruiz D, Ghisleni G, Rego N, Arcas-García A, Vitureira N, Jansen K, Souza LM, Silva RA, Lara DR, Pannunzio B, Abin-Carriquiry JA, Amo-Aparicio J, Martin-Otal C, Naya H, McGavern DB, Sayós J, López-Vales R, Kaster MP, Peluffo H. CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6651-6662. doi: 10.1073/pnas.1911816117. Epub 2020 Mar 9. PMID: 32152116; PMCID: PMC7104369.