Abstract
Background: The inflammasome is hypothesised to be a key mediator of the response to physiological and psychological stressors, and its dysregulation could be implicated in the
development of major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1b and IL-18, two pro-inflammatory cytokines involved in neuroimmunomodulation, neuroinflammation, and neurodegeneration. In this study, mice
with genetic deficiency or pharmacological inhibition of caspase-1 (casp1) were screened for anxiety-like, depressive-like and locomotor activity at baseline and after chronic stress. The microbiota-gut-brain (MGB) axis is a complex multi-organ bidirectional signaling system between
the microbiota and the brain that plays a fundamental role in host physiology, homeostasis, development, metabolism and behavior. A growing body of work shows reproducible and consistent effects of microbial states on mice behavior, supporting a role for microbiota in
modulating behavior.
Methods: Mice with genetic deficiency or pharmacological inhibition of caspase 1 (casp1) were screened for anxiety-like, depressive-like and locomotor activity at baseline and after
chronic stress. Fecal pellets were collected and gut microbiota was evaluated in wild-type mice after stress with pharmacological inhibition of casp1 and compared to controls.
Results: Genetic deficiency of casp1 decreased depressive and anxiety-like behaviors, and increased locomotor activity and skills. Moreover, casp1 deficiency prevented the exacerbation of anxiety-like behaviors following chronic stress; furthermore, pharmacological casp1 antagonism
prevented stress-induced increase in depressive-like behavior. Restraint stress or pharmacological inhibition of casp1 affected fecal microbiome composition and were both
associated with a dysbiotic state. Analysis of individual bacterial taxon relative abundance provided evidence of both synergistic and antagonistic effects of chronic restraint
and casp1 inhibition.
Conclusions: Casp1 inhibition has a protective effect modulating the relationship between stress and microbiota composition, which support the concept of a microbiota-gut-inflammasome-brain (MGIB) axis, in which the gut microbiota via the inflammasome signaling platform modulates inflammatory pathways that will alter brain function and affect anxiety- and depressive-like behaviors. Our data suggest that the MGIB
development of major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1b and IL-18, two pro-inflammatory cytokines involved in neuroimmunomodulation, neuroinflammation, and neurodegeneration. In this study, mice
with genetic deficiency or pharmacological inhibition of caspase-1 (casp1) were screened for anxiety-like, depressive-like and locomotor activity at baseline and after chronic stress. The microbiota-gut-brain (MGB) axis is a complex multi-organ bidirectional signaling system between
the microbiota and the brain that plays a fundamental role in host physiology, homeostasis, development, metabolism and behavior. A growing body of work shows reproducible and consistent effects of microbial states on mice behavior, supporting a role for microbiota in
modulating behavior.
Methods: Mice with genetic deficiency or pharmacological inhibition of caspase 1 (casp1) were screened for anxiety-like, depressive-like and locomotor activity at baseline and after
chronic stress. Fecal pellets were collected and gut microbiota was evaluated in wild-type mice after stress with pharmacological inhibition of casp1 and compared to controls.
Results: Genetic deficiency of casp1 decreased depressive and anxiety-like behaviors, and increased locomotor activity and skills. Moreover, casp1 deficiency prevented the exacerbation of anxiety-like behaviors following chronic stress; furthermore, pharmacological casp1 antagonism
prevented stress-induced increase in depressive-like behavior. Restraint stress or pharmacological inhibition of casp1 affected fecal microbiome composition and were both
associated with a dysbiotic state. Analysis of individual bacterial taxon relative abundance provided evidence of both synergistic and antagonistic effects of chronic restraint
and casp1 inhibition.
Conclusions: Casp1 inhibition has a protective effect modulating the relationship between stress and microbiota composition, which support the concept of a microbiota-gut-inflammasome-brain (MGIB) axis, in which the gut microbiota via the inflammasome signaling platform modulates inflammatory pathways that will alter brain function and affect anxiety- and depressive-like behaviors. Our data suggest that the MGIB
| Original language | English |
|---|---|
| Publication status | Published or Issued - Dec 2015 |
| Event | 54th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) - Hollywood, United States Duration: 6 Dec 2015 → 10 Dec 2015 |
Conference
| Conference | 54th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) |
|---|---|
| Country/Territory | United States |
| City | Hollywood |
| Period | 6/12/15 → 10/12/15 |