Neurobiology of disease
December 1, 2023
Youge Qu, Akifumi Eguchi, Li Ma et al.
26 citations
Pretreatment with MDMA for 14 days blocked anhedonia-like behavior and reduced synaptic proteins and brain-derived neurotrophic factor in the prefrontal cortex of mice exposed to chronic restraint stress. Cutting the subdiaphragmatic vagus nerve (vagotomy) blocked these beneficial effects. The gut microbiome showed differences in α-diversity between groups, and specific microbes varied between vehicle- and MDMA-treated stressed mice. Vagotomy prevented increases in three plasma compounds seen in MDMA-treated stressed mice, and two of those compounds correlated positively with several microbes. The data suggest that the gut-brain axis via the subdiaphragmatic vagus nerve may contribute to MDMA-induced stress resilience.
Pharmacology, biochemistry, and behavior
December 1, 2023
Guilin Liu, Li Ma, Youge Qu et al.
16 citations
Arketamine, but not the psychedelic drugs DOI or lisuride, produced long-lasting prophylactic effects in mouse models of depression. Male mice pretreated with arketamine six days before an immune challenge (lipopolysaccharide, LPS) showed reduced body weight loss, less spleen enlargement, less immobility in a forced swim test, and higher levels of the synaptic protein PSD-95 in the prefrontal cortex compared to mice pretreated with DOI or lisuride. Similarly, arketamine given one day before seven days of chronic restraint stress prevented increased immobility, restored sucrose preference, and protected PSD-95 expression. DOI and lisuride did not show these protective effects.
Pharmacology, biochemistry, and behavior
May 1, 2024
Li Ma, Akifumi Eguchi, Guilin Liu et al.
11 citations
Pretreatment with the antidepressant arketamine prevented stress-induced body weight loss, increased behavioral despair, decreased sucrose preference, and reduced synaptic protein expression in the prefrontal cortex of male mice exposed to chronic restraint stress. Gut microbiota analysis indicated that arketamine may restore stress-related changes in microbial abundance. Metabolomics identified four blood metabolites altered between stress-exposed and arketamine-pretreated mice. Network analysis linked synaptic proteins in the prefrontal cortex with specific gut microbes and blood metabolites. These findings suggest that the gut-brain axis, including microbial metabolites, may partly underlie the sustained prophylactic effects of arketamine.
Pharmacology, biochemistry, and behavior
December 1, 2024
Guilin Liu, Li Ma, Akemi Sakamoto et al.
4 citations
A single dose of arketamine, the (R)-enantiomer of ketamine, reduced depression-like behavior and inflammation in mice given lipopolysaccharide (LPS), a bacterial toxin that triggers an immune response. Arketamine also prevented these effects when given six days before LPS. LPS lowered the proportion of γδ T cells in the spleen, and arketamine reversed this change and reduced spleen enlargement and interleukin-6 levels. Blocking γδ T cells with an antibody eliminated arketamine's benefits, suggesting these immune cells are essential for its effects. The findings indicate splenic γδ T cells may be a new target for treating inflammation-related depression.