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Inhibition of stress resilience and adult hippocampal neurogenesis by platelet-derived LPA16:0 in anxiety

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Τίτλος: Inhibition of stress resilience and adult hippocampal neurogenesis by platelet-derived LPA16:0 in anxiety
Συγγραφείς: Larrieu, Thomas, Grieco, Fabio, Carron, Charline, Vilademunt, Marta, Weber, Crystal, Ginggen, Kyllian, Delacrétaz, Aurélie, Gallart-Ayala, Hector, Tsuda, Mumeko C, Cameron, Heather A, Eap, Chin B, Ivanisevic, Julijana, Magistretti, Pierre, Salta, Evgenia, Tosoni, Giorgia, Ayyildiz, Dilara, Telley, Ludovic, Dayer, Alexandre, Piguet, Camille, Toni, Nicolas
Πηγή: Larrieu, T, Grieco, F, Carron, C, Vilademunt, M, Weber, C, Ginggen, K, Delacrétaz, A, Gallart-Ayala, H, Tsuda, M C, Cameron, H A, Eap, C B, Ivanisevic, J, Magistretti, P, Salta, E, Tosoni, G, Ayyildiz, D, Telley, L, Dayer, A, Piguet, C & Toni, N 2026, 'Inhibition of stress resilience and adult hippocampal neurogenesis by platelet-derived LPA16:0 in anxiety', Nature Communications, vol. 17, 2424. https://doi.org/10.1038/s41467-026-69240-3
Έτος έκδοσης: 2026
Συλλογή: KNAW: Research Explorer (Koninklijke Nederlandse Akademie van Wetenschappen / Royal Netherlands Academy of Arts and Sciences)
Περιγραφή: Anxiety is an aggravating comorbidity of many psychiatric disorders that is often underdiagnosed and undertreated, and little is known on the mechanisms underlying its regulation. Here, we find that serum LPA16:0 abundance increases with trait anxiety in both humans and mice; while high LPA16:0 levels are sufficient to reduce the in vitro proliferation of adult hippocampal neural stem/progenitor cells. In humans, the main LPA receptor LPA1, bears single nucleotide polymorphism variants associated with anxiety. In mice, LPA16:0 decreases hippocampal neurogenesis and stress resilience, whereas LPA1 antagonism or the reduction of platelets, the main source of circulating LPA16:0, increases adult neurogenesis and resilience to acute stress. Conditional knockdown of LPA₁ receptor in neural stem cells is sufficient to enhance cell proliferation in the dentate gyrus. Finally, the inhibition of adult neurogenesis abolishes the beneficial effect of LPA1 antagonism on resilience against both acute and chronic stress. Together, these findings identify circulating LPA16:0 as a biomarker of trait anxiety and LPA16:0-LPA1 signaling as a regulation mechanism of mood-related behavior through the decrease of adult neurogenesis.
Τύπος εγγράφου: article in journal/newspaper
Περιγραφή αρχείου: application/pdf
Γλώσσα: English
ISSN: 2041-1723
Relation: info:eu-repo/semantics/altIdentifier/pmid/41651838; info:eu-repo/semantics/altIdentifier/hdl/https://hdl.handle.net/20.500.11755/76934a99-8f64-4ef0-9918-36f82db99583; info:eu-repo/semantics/altIdentifier/pissn/2041-1723
DOI: 10.1038/s41467-026-69240-3
Διαθεσιμότητα: https://pure.knaw.nl/portal/en/publications/76934a99-8f64-4ef0-9918-36f82db99583
https://doi.org/10.1038/s41467-026-69240-3
https://hdl.handle.net/20.500.11755/76934a99-8f64-4ef0-9918-36f82db99583
https://pure.knaw.nl/ws/files/2428516974/Larrieu2026.pdf
Rights: info:eu-repo/semantics/openAccess
Αριθμός Καταχώρησης: edsbas.615C8863
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  – Url: https://dx.doi.org/doi:10.1038/s41467-026-69240-3
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  Data: Anxiety is an aggravating comorbidity of many psychiatric disorders that is often underdiagnosed and undertreated, and little is known on the mechanisms underlying its regulation. Here, we find that serum LPA16:0 abundance increases with trait anxiety in both humans and mice; while high LPA16:0 levels are sufficient to reduce the in vitro proliferation of adult hippocampal neural stem/progenitor cells. In humans, the main LPA receptor LPA1, bears single nucleotide polymorphism variants associated with anxiety. In mice, LPA16:0 decreases hippocampal neurogenesis and stress resilience, whereas LPA1 antagonism or the reduction of platelets, the main source of circulating LPA16:0, increases adult neurogenesis and resilience to acute stress. Conditional knockdown of LPA₁ receptor in neural stem cells is sufficient to enhance cell proliferation in the dentate gyrus. Finally, the inhibition of adult neurogenesis abolishes the beneficial effect of LPA1 antagonism on resilience against both acute and chronic stress. Together, these findings identify circulating LPA16:0 as a biomarker of trait anxiety and LPA16:0-LPA1 signaling as a regulation mechanism of mood-related behavior through the decrease of adult neurogenesis.
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