Inflammasome Activation in the Brain: Impact on Depressive-Like Behaviour

Julio Licinio, Antonio Inserra, Martin Lewis, Chenglong Yu, Claudio A. Mastronardi, Geraint Rogers, Lex Leong, Jocelyn Choo, Steven Wesselingh, Ma-Li Wong

Research output: Contribution to conferencePosterpeer-review


Background: Inflammasome activation causes the matura- tion of caspase-1 (casp1, aka interleukin converting enzyme), an enzyme that plays a role in a number of physiological and pathophysiological processes both in the CNS and periphery (i.e., immune response, microglia activation, LTP, synaptic plasticity, adipocyte differentiation, chronic inflammation). We investigated the behavioural phenotype of genetic deficiency and pharmacological inhibition of caspase 1 at baseline and after chronic stress. We also studied simulta- neous gut microbiota changes.

Methods: Adult male mice (WT and casp1 knockout) were submitted to a battery of behavioural tests at baseline and after chronic restraint stress (4 h/day for 3 weeks). Forced swim test, open field test, novelty suppressed feeding, elevated plus maze, sucrose preference test and rotarod were performed. Fecal pellets were collected and used in 16S rRNA gene amplicon sequencing.

Results: Genetic caspase-1 deficiency decreased depressive- and anxiety-like behaviors, and increased locomotor activity. Pharmacological caspase-1 antagonism improved stress- induced depressive like behaviour; fecal microbiota profiling with 16S rRNA showed increased in the relative abundance of the genus Akkermansia and Blautia. We will present new metagenomics data disclosing the bacteria species involved and their network analysis. 
Conclusions: The protective effect of caspase-1 inhibition in the exacerbation of post-stress depressive-like behaviour may involve the modulation of the relationship between stress and gut microbiota composition via inflammasome signal- ling pathways. We propose that the gut-microbiota- inflammasome-brain axis may be a viable novel therapeutic target for depression.
Original languageEnglish
Number of pages1
Publication statusPublished or Issued - 2016
EventAmerican College of Neuropsychopharmacology (ACNP) 55th Annual Meeting - Florida, United States
Duration: 4 Dec 20168 Dec 2016
Conference number: 55th


ConferenceAmerican College of Neuropsychopharmacology (ACNP) 55th Annual Meeting
Abbreviated titleACNP
Country/TerritoryUnited States
Internet address

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