Reduced anxiety-like behavior and central neurochemical change in germ-free mice: Behavior in germ-free mice

In the citing paper

“For example, some studies involving GF Swiss Webster mice show a decreased anxiety-like behavior (Arentsen et al., 2018;Clarke et al., 2013;Neufeld et al., 2011) whereas the opposite has been found in male GF BALB/c mice (Chen et al., 2017b;Nishino et al., 2013).”

In the citing paper

“Due to the lack of commensal microbes, GF animals have impaired immune systems, dysregulated hormone signaling, altered metabolism, and differences in neurotransmission from conventional counterparts (Kawase et al., 2017;Neufeld et al., 2011;Pan et al., 2018;Sudo et al., 2004;Weger et al., 2019).”

In the citing paper

“GF studies also show that microbes can also regulate NMDA receptors (NMDAR) (Neufeld et al., 2011)”

In the citing paper

“In addition, expression of NMDAR and BDNF is significantly reduced in GF mice [572, 581, 582]”

In the citing paper

“Preliminary studies have demonstrated that alterations in the GI microbiota can lead to long-term increased anxiety (69, 115, 116) and altered exploratory behavior in mice (18, 19).”

In the citing paper

“microbial abundance has been shown to alter the expression of neurotransmitter receptors in the brain (51, 189, 191).”

In the citing paper

“These findings have subsequently been reproduced, with both male and female mice demonstrating enhanced stress reactivity to a novel environmental stressors (189, 350, 351).”

In the citing paper

“Indeed, germ-free animals show widespread neurodevelopmental changes, associated with alterations in monoaminergic neurotransmission in the CNS (189).”

In the citing paper

“These changes include increased hippocampal dopamine D1 receptor mRNA levels and decreased dopamine D1 receptor in the striatum and nucleus accumbens, as well as increased serotonin in the blood and hippocampus, with decreased serotonin receptor expression, respectively.”

In the citing paper

“Behavioral differences in germ-free mice include their anxiolytic-like manner when compared to SPF controls, although some studies report increased anxiety-like behavior in different species (124, 189, 351, 376).”

In the citing paper

“Several metabolomic studies show alterations in the dopamine and serotonin systems (124, 189, 350, 378–380).”

In the citing paper

“Interestingly, these cognitive deficits in rodents can be corrected through the colonization of the intestine via a fecal transplant from the control group, but only if it occurs early in life.”

In the citing paper

“These studies show that rodents lacking all gut bacteria from birth (germ-free animals) have memory deficits28 and behavioral abnormalities29, 30 when compared to animals with normal gut microbiota.”

In the citing paper

“Early experiments using germ-free (GF) or specific pathogen-free (SPF) mice treated with antibiotics, to reduce the microbial diversity within the intestine, showed that several neurological problems occur in mice with reduced or lack of proper mature gut microbiota (7, 10, 14, 15, 34, 80, 81).”

In the citing paper

“In details, compared to colonized mice, GF mice showed exaggerated hypothalamic–pituitary–adrenal (HPA) restrain stress reaction (10), impared social behaviors (12, 15, 82), reduced anxiety-like behavior (7, 81–83) and increased motor and rearing activity (80, 84).”

In the citing paper

“The developmental abnormalities found in GF mice are totally reversible by colonization with intestinal bacteria early in life but not in adulthood, suggesting that the microbiome influences brain development.9,10”

In the citing paper

“Some investigations have shown neurochemical changes as a result of gut microbiome dysfunction, such as altered levels of brain-derived neurotropic factor (BDNF), reduced serotonin receptor expression, reduced synaptic plasticity gene expression, and increased striatal monoamine turnover [10–12].”

In the citing paper

“GF mouse models have shown that the serotonergic system in the brain is also influenced by the microbiota [24, 26], whereby excess peripheral Trp may cross the BBB to influence the rate serotonin synthesis in the brain [108].”

In the citing paper

“These findings suggest that gut microbes not only regulate gene expression in the mouse brain (Hoban et al., 2016; Neufeld et al., 2011; Stilling et al., 2015), but also affect alternative splicing (Stilling et al., 2018), and can regulate the production of specific isoforms of genes that have been implicated in ASD.”

In the citing paper

“In particular, studies using GF animals that demonstrated aberrant behavior and neurochemical profile were critical in establishing the link between the gut microbiota and brain development and processes (211-217).”

In the citing paper

“Animal studies have demonstrated that the gut microbiota plays a crucial role in anxiety (Neufeld et al., 2011), cognitive performance (Desbonnet et al., 2015), repetitive behaviors (Desbonnet et al., 2014) and social communications (Buffington et al., 2016; Sherwin et al., 2017).”