Changes in microglial activation within the hindbrain, nodose ganglia, and the spinal cord following subdiaphragmatic vagotomy

Gallaher, Zachary R.; Ryu, Vitaly; Herzog, Thiebaut; Ritter, Robert C.; Czaja, Krzysztof

doi:10.1016/j.neulet.2012.01.079

Cited by 42 publications

(39 citation statements)

References 49 publications

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“…Interestingly, our previous studies revealed that damage to peripheral axons of the vagus (subdiaphragmatic vagotomy) also induced transient decrease in the density of vagal afferents projecting to the NTS (Ballsmider et al 2015, Peters et al 2013) followed by vagal inputs sprouting. Vagal damage also resulted in microglia activation in the NTS and DMV (Gallaher et al 2012). We previously found that vagal afferent remodeling led to alterations in frequency and amplitude of glutamate release in the NTS (Peters et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted the above study minocycline was administered directly into the spinal cord at a dose of 10, 50 or 100 μg/kg. Direct anti-inflammatory effects of minocycline have been reported for doses ranging from 20 to 100 mg/kg (Amin et al 2015, Gallaher et al 2012, Kumar and Addepalli 2011). Minocycline may alleviate inflammation via a decrease in bacteria-driven cytokine production.…”

Section: Discussionmentioning

confidence: 99%

“…For visualization of vagal afferents, the hindbrain sections were incubated with isolectin B4 biotin-conjugated antibody (IB4, 1:400, cat# B-1205, Vector Laboratories, CA) for 12 h at room temperature (Shehab 2009), followed by ExtrAvidin-CY3 (1:600, E-4142, Sigma-Aldrich) for 2 h. Negative controls were performed by omission of primary antibodies. Sections were mounted in ProLong (Molecular Probes, OR) and examined under Nikon 80-I fluorescent microscope as previously described (Gallaher et al 2012, Peters et al 2013). …”

Section: Methodsmentioning

confidence: 99%

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Energy‑dense diet triggers changes in gut microbiota, reorganization of gut‑brain vagal communication and increases body fat accumulation

Vaughn¹,

Cooper²,

Lorenzo³

et al. 2017

Acta Neurobiologiae Experimentalis

130

105

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Obesity is associated with consumption of energy-dense diets and development of systemic inflammation. Gut microbiota play a role in energy harvest and inflammation and can influence the change from lean to obese phenotypes. The nucleus of the solitary tract (NTS) is a brain target for gastrointestinal signals modulating satiety and alterations in gut-brain vagal pathway may promote overeating and obesity. Therefore, we tested the hypothesis that high-fat diet-induced changes in gut microbiota alter vagal gut-brain communication associated with increased body fat accumulation. Sprague-Dawley rats consumed a low energy-dense rodent diet (LFD; 3.1 kcal/g) or high energy-dense diet (HFD, 5.24 kcal/g). Minocycline was used to manipulate gut microbiota composition. 16S Sequencing was used to determine microbiota composition. Immunofluorescence against IB4 and Iba1 was used to determine NTS reorganization and microglia activation. Nodose ganglia from LFD rats were isolated and co-cultured with different bacteria strains to determine neurotoxicity. HFD altered gut microbiota with increases in Firmicutes/Bacteriodetes ratio and in pro-inflammatory Proteobacteria proliferation. HFD triggered reorganization of vagal afferents and microglia activation in the NTS, associated with weight gain. Minocycline-treated HFD rats exhibited microbiota profile comparable to LFD animals. Minocycline suppressed HFD-induced reorganization of vagal afferents and microglia activation in the NTS, and reduced body fat accumulation. Proteobacteria isolated from cecum of HFD rats were toxic to vagal afferent neurons in culture. Our findings show that diet-induced shift in gut microbiome may disrupt vagal gut-brain communication resulting in microglia activation and increased body fat accumulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Energy‑dense diet triggers changes in gut microbiota, reorganization of gut‑brain vagal communication and increases body fat accumulation

Vaughn¹,

Cooper²,

Lorenzo³

et al. 2017

Acta Neurobiologiae Experimentalis

130

105

View full text Add to dashboard Cite

show abstract

“…Electrophysiology also revealed transient decreases in spontaneous glutamate release, and the number of primary afferent inputs [52]. Other changes in the CNS induced by vagotomy, such as microglial activation within the hindbrain, nodose ganglia, and the spinal cord have also been described [53]. However, to our knowledge, no data about the potential role of subdiaphragmatic vagotomy on LTP has been previously described.…”

Section: Discussionmentioning

confidence: 99%

Dietary 2’-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents

et al. 2016

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2´-fucosyllactose (2´-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits.

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“…After blocking in 10% normal horse serum in Tris-phosphate buffered saline (TPBS, pH 7.4) sections were incubated overnight with a primary antibody against ionized calcium binding adaptor molecule 1 (Iba1) followed by an Alexa-488 secondary antibody (Invitrogen, CA) to visualize microglia activation as previously described [20]. The hindbrain sections were incubated with isolectin B4 biotin-conjugated (IB4) for 12 h at room temperature to visualize primary unmyelinated vagal afferents innervating the GI tract as previously described [21], followed by ExtrAvidin-CY3 (1:600, E-4142, Sigma-Aldrich) for 2 h. Negative controls were performed by omission of primary antibodies.…”

Section: Methodsmentioning

confidence: 99%

Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity

Sen

Cawthon

Ihde

et al. 2017

Physiology & Behavior

203

152

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Obesity is one of the major health issues in the United States. Consumption of diets rich in energy, notably from fats and sugars (high-fat/high-sugar diet: HF/HSD) is linked to the development of obesity and a popular dietary approach for weight loss is to reduce fat intake. Obesity research traditionally uses low and high fat diets and there has been limited investigation of the potential detrimental effects of a low-fat/high-sugar diet (LF/HSD) on body fat accumulation and health. Therefore, in the present study, we investigated the effects of HF/HSD and LF/HSD on microbiota composition, gut inflammation, gut-brain vagal communication and body fat accumulation. Specifically, we tested the hypothesis that LF/HSD changes the gut microbiota, induces gut inflammation and alters vagal gut-brain communication, associated with increased body fat accumulation. Sprague-Dawley rats were fed an HF/HSD, LF/HSD or control low-fat/low-sugar diet (LF/LSD) for 4 weeks. Body weight, caloric intake, and body composition were monitored daily and fecal samples were collected at baseline, 1, 6 and 27 days after the dietary switch. After four weeks, blood and tissues (gut, brain, liver and nodose ganglia) were sampled. Both HF/HSD and LF/HSD-fed rats displayed significant increases in body weight and body fat compared to LF/LSD-fed rats. 16S rRNA sequencing showed that both HF/HSD and LF/HSD-fed animals exhibited gut microbiota dysbiosis characterized by an overall decrease in bacterial diversity and an increase in Firmicutes/Bacteriodetes ratio. Dysbiosis was typified by a bloom in Clostridia and Bacilli and a marked decrease in Lactobacillus spp. LF/HSD-fed animals showed a specific increase in Sutterella and Bilophila, both Proteobacteria, abundances of which have been associated with liver damage. Expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNFα was upregulated in the cecum while levels of tight junction protein occludin were downregulated in both HF/HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation.

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Changes in microglial activation within the hindbrain, nodose ganglia, and the spinal cord following subdiaphragmatic vagotomy

Cited by 42 publications

References 49 publications

Energy‑dense diet triggers changes in gut microbiota, reorganization of gut‑brain vagal communication and increases body fat accumulation

Energy‑dense diet triggers changes in gut microbiota, reorganization of gut‑brain vagal communication and increases body fat accumulation

Dietary 2’-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents

Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity

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