Modulation of anxiety-like behavior in galactooligosaccharide-fed mice: A potential role for bacterial tryptophan metabolites and reduced microglial reactivity

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 121, P. 229 - 243

Published: July 26, 2024

Prebiotic galactooligosaccharides (GOS) reduce anxiety-like behaviors in mice and humans. However, the biological pathways behind these behavioral changes are not well understood. To begin to study pathways, we utilized C57BL/6 that were fed a standard diet with or without GOS supplementation for 3 weeks prior testing on open field. After testing, colonic contents serum collected bacteriome (16S rRNA gene sequencing, only) metabolome (UPLC-MS, data) analyses. As expected, significantly reduced behavior (i.e., increased time center) decreased cytokine expression (Tnfa Ccl2) prefrontal cortex. Notably, center of field was correlated methyl-indole-3-acetic acid (methyl-IAA). This metabolite is methylated form indole-3-acetic (IAA) derived from bacterial metabolism tryptophan. Sequencing analyses showed Lachnospiraceae UCG006 Akkermansia; taxa known metabolize both determine extent which methyl-IAA can affect behavior, intraperitoneally injected methyl-IAA. Mice given had reduction field, along lower Tnfa Methyl-IAA also found TNF-α (as as CCL2) production by LPS-stimulated BV2 microglia. Together, data support novel pathway through reduces suggests microglial chemokine production, turn behavior.

Language: Английский

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Post-weaning social isolation alters sociability in a sex-specific manner

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Aug. 29, 2024

Adolescence is a critical period for brain development in humans and stress exposure during this time can have lasting effects on behavior development. Social isolation loneliness are particularly salient stressors that lead to detrimental mental health outcomes females, although most of the preclinical work social has been done male animals. Our lab developed model post-weaning adolescent leads increased drug reward sensitivity altered neuronal structure limbic regions. The current study utilized determine impact three-chamber interaction task both adolescence adulthood. We found while does not alter (PND45), it sex-specific young adulthood (PND60), potentiating mice decreasing female mice. As early life activate microglia leading alterations pruning, we next examined inhibiting microglial activation with daily minocycline administration first 3 weeks these changes interaction. During adolescence, dampened mice, having no effect females. In contrast, adulthood, did males, socially isolated males exhibiting higher levels compared their group housed counterparts. treatment reversed group, mimicking what seen naïve males. Taken together, alters but

Language: Английский

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Cytokines and Chemokines in the Nervous System in Health and Disease

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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Cerebellar microglia: On the edge between neuroinflammation and neuroregulation

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 21(1), P. 156 - 172

Published: Oct. 22, 2024

The cerebellum is receiving increasing attention for its cognitive, emotional, and social functions, as well unique metabolic profiles. Cerebellar microglia exhibit specialized highly immunogenic phenotypes under both physiological pathological conditions. These immune cells communicate with intrinsic systemic factors contribute to the structural functional compartmentalization of cerebellum. In this review, we discuss roles in cerebellar microenvironment, neuroinflammation, adaptation, neuronal activity, associated molecular cellular mechanisms, potential therapeutic strategies targeting context neuroinflammation. Future directions unresolved questions field are further highlighted, particularly regarding interventions microglia, mechanisms activities circuitry, connectivity, neurofunctional outcomes their activity. morphology performance influenced by that actively monitored healthy diseased states. Under conditions, local subsets diverse responses altered microenvironment Microglia undergo early maturation during embryonic stage display specialized, phenotypes. summary, have capacity serve regulatory tools influence across a wide range neurological including neurodevelopmental, neurodegenerative, metabolic, stress-related disorders.

Language: Английский

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Excision of mesenteric lymph nodes alters gut microbiota and impairs social dominance in adult mice

Brain and Behavior, Journal Year: 2023, Volume and Issue: 13(7)

Published: May 8, 2023

Introduction Mesenteric lymph nodes (MLNs) are central in immune anatomy. MLNs associated with the composition of gut microbiota, affecting system and system. Gut microbiota was found to differ among individuals different social hierarchies. Nowadays, excision is more frequently involved gastrointestinal surgery; however, potential side effects on dominance still unknown. Methods were removed from male mice (7–8 weeks old). Four after MLN removal, test performed investigate dominance; hippocampal serum interleukin (IL)‐1β, IL‐10, tumor necrosis factor‐alpha (TNF‐α) investigated; histopathology used evaluate local inflammation ileum. The then examined understand possible mechanism, finally intraperitoneal injection IL‐10 validate effect dominance. Results There a decrease operation group compared control group, as well levels, but no difference IL‐1β TNF‐α ileum removal. 16S rRNA sequencing analysis showed that relative abundance class Clostridia decreased group. This positively levels. Furthermore, subset increased Conclusions Our findings suggested contributed maintaining dominance, which might be reduced imbalance specific flora microbiota.

Language: Английский

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