bioRxiv ScienceSearch

Biology subjects

Mondo, E.

Publications and source records attributed to Mondo, E..

2 recordsLinked to original sources

Gut microbiome structure and adrenocortical activity in dogs with aggressive and phobic behavioral disorders

Accompanying human beings since the Paleolithic period, dogs has been recently regarded as a reliable model for the study of the gut microbiome connections with health and disease. In order to provide some glimpses on the connections between the gut microbiome layout and host behavior, we profiled the phylogenetic composition and structure of the canine gut microbiome of dogs with aggressive (n = 17), phobic (n = 15) and normal behavior (n = 17). According to our findings, aggressive behavioral disorder was found to be characterized by a peculiar gut microbiome structure, with high biodiversity and enrichment in generally subdominant bacterial genera. On the other hand, phobic dogs were enriched in Lactobacillus, a bacterial genus with known probiotic and psychobiotic properties. Although further studies are needed to validate our findings, our work supports the intriguing opportunity that different behavioral phenotypes in dogs may be associated with peculiar gut microbiome layouts, suggesting possible connections between the gut microbiome and the central nervous system and indicating the possible adoption of probiotic interventions aimed at restoring a balanced host-symbiont interplay for mitigating behavioral disorders.

microbiology

Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling

Microglia rapidly respond to changes in neural activity and inflammation to regulate synaptic connectivity. The extracellular signals, particularly neuron-derived molecules, that drive these microglial functions at synapses remains a key open question. Here, whisker lesioning, known to dampen cortical activity, induces microglia-mediated synapse elimination. We show that this synapse elimination is dependent on the microglial fractalkine receptor, CX3CR1, but not complement receptor 3, signaling. Further, mice deficient in the CX3CR1 ligand (CX3CL1) also have profound defects in synapse elimination. Single-cell RNAseq then revealed that Cx3cl1 is cortical neuron-derived and ADAM10, a metalloprotease that cleaves CX3CL1 into a secreted form, is upregulated specifically in layer IV neurons and microglia following whisker lesioning. Finally, inhibition of ADAM10 phenocopies Cx3cr1-/- and Cx3cl1-/- synapse elimination defects. Together, these results identify novel neuron-to-microglia signaling necessary for cortical synaptic remodeling and reveal context-dependent immune mechanisms are utilized to remodel synapses in the mammalian brain.

neuroscience