Both increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. We have previously described how interleukin-1 (IL-1) β, a pro-inflammatory cytokine increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. Here, using the same human in vitro model, we show how omega-3 (ω-3) polyunsaturated fatty acids and conventional antidepressants reverse this reduction in neurogenesis, while differentially affecting the kynurenine pathway. We allowed neural cells to proliferate for 3 days and further differentiate for 7 days in the presence of IL-1β (10 ng/ml) and either the selective serotonin reuptake inhibitor sertraline (1 µM), the serotonin and norepinephrine reuptake inhibitor venlafaxine (1 µM), or the ω-3 fatty acids eicosapentaenoic acid (EPA, 10 µM) or docosahexaenoic acid (DHA, 10 µM). Co-incubation with each of these compounds reversed the IL-1β-induced reduction in neurogenesis (DCX- and MAP2-positive neurons), indicative of a protective effect. Moreover, EPA and DHA also reversed the IL-1β-induced increase in kynurenine, as well as mRNA levels of indolamine-2,3-dioxygenase (IDO); while DHA and sertraline reverted the IL-1β-induced increase in quinolinic acid and mRNA levels of kynurenine 3-monooxygenase (KMO). Our results show common effects of monoaminergic antidepressants and ω-3 fatty acids on the reduction of neurogenesis caused by IL-1β, but acting through both common and different kynurenine pathway-related mechanisms. Further characterization of their individual properties will be of benefit towards improving a future personalized medicine approach.

Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants / Borsini, Alessandra; Alboni, Silvia; Horowitz, Mark A.; Tojo, Luis M.; Cannazza, Giuseppe; Su, Kuan-Pin; Pariante, Carmine M.; Zunszain, Patricia A.. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 65:(2017), pp. 230-238. [10.1016/j.bbi.2017.05.006]

Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants

Alboni, Silvia;Cannazza, Giuseppe;
2017

Abstract

Both increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. We have previously described how interleukin-1 (IL-1) β, a pro-inflammatory cytokine increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. Here, using the same human in vitro model, we show how omega-3 (ω-3) polyunsaturated fatty acids and conventional antidepressants reverse this reduction in neurogenesis, while differentially affecting the kynurenine pathway. We allowed neural cells to proliferate for 3 days and further differentiate for 7 days in the presence of IL-1β (10 ng/ml) and either the selective serotonin reuptake inhibitor sertraline (1 µM), the serotonin and norepinephrine reuptake inhibitor venlafaxine (1 µM), or the ω-3 fatty acids eicosapentaenoic acid (EPA, 10 µM) or docosahexaenoic acid (DHA, 10 µM). Co-incubation with each of these compounds reversed the IL-1β-induced reduction in neurogenesis (DCX- and MAP2-positive neurons), indicative of a protective effect. Moreover, EPA and DHA also reversed the IL-1β-induced increase in kynurenine, as well as mRNA levels of indolamine-2,3-dioxygenase (IDO); while DHA and sertraline reverted the IL-1β-induced increase in quinolinic acid and mRNA levels of kynurenine 3-monooxygenase (KMO). Our results show common effects of monoaminergic antidepressants and ω-3 fatty acids on the reduction of neurogenesis caused by IL-1β, but acting through both common and different kynurenine pathway-related mechanisms. Further characterization of their individual properties will be of benefit towards improving a future personalized medicine approach.
2017
18-mag-2017
65
230
238
Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants / Borsini, Alessandra; Alboni, Silvia; Horowitz, Mark A.; Tojo, Luis M.; Cannazza, Giuseppe; Su, Kuan-Pin; Pariante, Carmine M.; Zunszain, Patricia A.. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 65:(2017), pp. 230-238. [10.1016/j.bbi.2017.05.006]
Borsini, Alessandra; Alboni, Silvia; Horowitz, Mark A.; Tojo, Luis M.; Cannazza, Giuseppe; Su, Kuan-Pin; Pariante, Carmine M.; Zunszain, Patricia A.
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0889159117301526-main.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 811.8 kB
Formato Adobe PDF
811.8 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1159108
Citazioni
  • ???jsp.display-item.citation.pmc??? 57
  • Scopus 90
  • ???jsp.display-item.citation.isi??? 85
social impact