Absence of gut microbiota influences lipopolysaccharide-induced behavioral changes in mice.
Changes in the microbiota composition of gastrointestinal tract are emerging as potential players in the physiopathology of neuropsychiatric disorders. In the present work we evaluated the relationship between the absence of gut microbiota and neuroinflammatory mechanisms in a murine model of LPS-induced behavioral alterations. Germ-free (GF) or conventional male mice received a single i.p. injection of lipopolysaccharide (LPS i.p.; 0.83mg/Kg) or PBS, and after 24h they were tested for depressive-like behaviors (forced swimming test, tail suspension test - TST, or sucrose preference test - SPT). After behavioral evaluation, animals were analyzed for possible changes in neuroplasticity by means of BDNF, NGF and cytokines levels in prefrontal cortex and hippocampus, and the expression of Iba-1 (microglial activation marker) in the hippocampus, and the cellular activity marker, ΔFosB, in the dorsal raphe nucleus. In conventional mice, LPS induced depressive-like behaviors. LPS-induced changes were followed by up-regulation of the expression of TNF and Iba-1 in the hippocampus. The same effects were not observed in GF mice. Behavioral effects of LPS were not observed in GF mice submitted to TST. GF mice present a lower response to the anhedonia-like effect induced by LPS when compared to conventional animals (SPT). There was up-regulation of ΔFosB in the dorsal raphe nucleus in the absence of gut microbiota, events not influenced by LPS treatment. Our results suggest that gut-microbiota interactions influence depressive-like behaviors, raphe nucleus activation and activation of pro-inflammatory mechanisms within the hippocampus.
Infectious Disease and Tropical Medicine Graduate Program, School of Medicine, UFMG, Belo Horizonte, MG, Brazil; Department of Pharmacology, School of Medicine of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
Alline C
AC
Campos
Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Natalia P
NP
Rocha
Department of Microbiology, Institute of Biological Sciences, UFMG, Belo Horizonte, MG, Brazil.
Jacques R
JR
Nicoli
Department of Biochemistry and Immunology, Institute of Biological Sciences, UFMG, Belo Horizonte, MG, Brazil.
Leda Q
LQ
Vieira
Infectious Disease and Tropical Medicine Graduate Program, School of Medicine, UFMG, Belo Horizonte, MG, Brazil; Department of Biochemistry and Immunology, Institute of Biological Sciences, UFMG, Belo Horizonte, MG, Brazil.
Mauro M
MM
Teixeira
Infectious Disease and Tropical Medicine Graduate Program, School of Medicine, UFMG, Belo Horizonte, MG, Brazil; Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: altexr@gmail.com.
Antonio L
AL
Teixeira
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects; D003863:Depression / Q000139:chemically induced / Q000378:metabolism*; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000378:metabolism*; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D020932:Nerve Growth Factor
Cytokines; Gut microbiota; Microglia; Raphe nucleus; Sickness behavior