TY - JOUR
T1 - Role of gut microbiota in the GBR12909 model of mania-like behavior in mice
AU - de Miranda, Aline Silva
AU - Vieira, Érica Leandro Marciano
AU - dos Reis Bastos, Juliana
AU - Ferreira, Rodrigo Novaes
AU - Nicoli, Jacques R.
AU - Teixeira, Mauro Martins
AU - Vieira, Leda Quercia
AU - Moreira, Fabrício A.
AU - Teixeira, Antônio Lúcio
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/9/15
Y1 - 2020/9/15
N2 - Growing evidence suggests a role for brain-gut-microbiota axis in affective disorders including major depression and bipolar disorder (BD). Herein, we aim to explore, by employing germ-free (GF) mice, the effect of the indigenous microbiota in the development of mania-like behavior. Conventional and GF mice were evaluated for the hyperlocomotion induced by the dopamine transporter inhibitor GBR12909 (15 mg/Kg), a validated model for mania-like behavior. Inflammatory mediators and neurotrophic factors were quantified in the prefrontal cortex, hippocampus and striatum. Mice lacking indigenous microbiota were less susceptible to the mania-like behavior induced by GBR12909. This effect was associated with decreased levels of inflammatory cytokines such as IL-6 and TNF-α, along with increased concentrations of anti- inflammatory cytokines (IL-10) and of neurotrophins (BDNF and NGF). We provided the first evidence that gut-microbiota-brain axis participates in the development of mania-like behavior in rodents, possibly through neuroimmunepathways.
AB - Growing evidence suggests a role for brain-gut-microbiota axis in affective disorders including major depression and bipolar disorder (BD). Herein, we aim to explore, by employing germ-free (GF) mice, the effect of the indigenous microbiota in the development of mania-like behavior. Conventional and GF mice were evaluated for the hyperlocomotion induced by the dopamine transporter inhibitor GBR12909 (15 mg/Kg), a validated model for mania-like behavior. Inflammatory mediators and neurotrophic factors were quantified in the prefrontal cortex, hippocampus and striatum. Mice lacking indigenous microbiota were less susceptible to the mania-like behavior induced by GBR12909. This effect was associated with decreased levels of inflammatory cytokines such as IL-6 and TNF-α, along with increased concentrations of anti- inflammatory cytokines (IL-10) and of neurotrophins (BDNF and NGF). We provided the first evidence that gut-microbiota-brain axis participates in the development of mania-like behavior in rodents, possibly through neuroimmunepathways.
KW - Bipolar disorder
KW - GBR12909
KW - Gut-microbiota-brain axis
KW - Inflammation
KW - Mania
KW - Neurotrophic factors
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U2 - 10.1016/j.jneuroim.2020.577292
DO - 10.1016/j.jneuroim.2020.577292
M3 - Article
C2 - 32580070
AN - SCOPUS:85086644428
SN - 0165-5728
VL - 346
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
M1 - 577292
ER -