https://doi.org/10.1016/j.neuropharm.2022.109219

Arketamine, a new rapid-acting antidepressant: A historical review and future directions

Brain-spleen axis in health and diseases: A review and future perspective

The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR: coded by Chrna7) is known to regulate the cholinergic ascending anti-inflammatory pathway. We previously reported that Chrna7 knock-out (KO) mice show depression-like behaviors through abnormal composition of gut microbiota and systemic inflammation. Given the role of subdiaphragmatic vagus nerve in gut–microbiota–brain axis, we investigated whether subdiaphragmatic vagotomy (SDV) could affect depression-like behaviors, abnormal composition of gut microbiota, and microbes-derived metabolites in Chrna7 KO mice. SDV blocked depression-like behaviors and reduced expression of synaptic proteins in the medial prefrontal cortex (mPFC) of Chrna7 KO mice. LEfSe (linear discriminant analysis effect size) analysis revealed that the species Lactobacillus sp. BL302, the species Lactobacillus hominis, and the species Lactobacillus reuteri, were identified as potential microbial markers in the KO + SDV group. There were several genus and species altered among the three groups [wild-type (WT) + sham group, KO + sham group, KO + SDV group]. Furthermore, there were several plasma metabolites altered among the three groups. Moreover, there were correlations between relative abundance of several microbiome and behavioral data (or synaptic proteins). Network analysis showed correlations between relative abundance of several microbiome and plasma metabolites (or behavioral data). These data suggest that Chrna7 KO mice produce depression-like behaviors and reduced expression of synaptic proteins in the mPFC through gut–microbiota–brain axis via subdiaphragmatic vagus nerve. 

A role of gut–microbiota–brain axis via subdiaphragmatic vagus nerve in depression-like phenotypes in Chrna7 knock-out mice

A role of microRNA-149 in the prefrontal cortex for prophylactic actions of (R)-ketamine in inflammation model

Ketamine and its metabolites: Potential as novel treatments for depression

http://manuscript.elsevier.com/S0028390822001988/pdf/S0028390822001988.pdf

Effects of (R)-ketamine on reduced bone mineral density in ovariectomized mice: A role of gut microbiota

https://doi.org/10.1016/j.nbd.2022.105635

(R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: A role of gut–microbiota–brain axis

(R, S)-ketamine has prophylactic antidepressant-like effects in rodents; however, the precise molecular mechanisms underlying its action remain unknown. Using RNA-sequencing analysis, we searched novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R, S)-ketamine. Pretreatment with (R)-ketamine (10 mg/kg, 6 days before) significantly ameliorated body weight loss, splenomegaly, and increased immobility time of forced swimming test in lipopolysaccharide (LPS: 1.0 mg/kg)-treated mice. RNA-sequencing analysis of prefrontal cortex (PFC) and subsequent IPA (Ingenuity Pathway Analysis) revealed that the nuclear factor of activated T cells 4 (NFATc4) signaling might contribute to sustained prophylactic effects of (R)-ketamine. Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated the increased gene expression of NFATc4 signaling (Nfatc4, Cd4, Cd79b, H2-ab1, H2-aa) in the PFC of LPS-treated mice. Furthermore, pretreatment with NFAT inhibitors (i.e., NFAT inhibitor and cyclosporin A) showed prophylactic effects in the LPS-treated mice. Similar to (R)-ketamine, gene knockdown of Nfatc4 gene by bilateral injection of adeno-associated virus (AAV) into the mPFC could elicit prophylactic effects in the LPS-treated mice. In conclusion, our data implicate a novel NFATc4 signaling pathway in the PFC underlying the prophylactic effects of (R)-ketamine for inflammation-related depression. 

/pdf/nuclear-factor-of-activated-t-cells-4-in-the-prefrontal-3e9wgwup.pdf

Xingming Wang

Papers

Effects of (R)-ketamine on reduced bone mineral density in ovariectomized mice: A role of gut microbiota

(R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: A role of gut–microbiota–brain axis

Nuclear factor of activated T cells 4 in the prefrontal cortex is required for prophylactic actions of (R)-ketamine

A role of gut–microbiota–brain axis via subdiaphragmatic vagus nerve in depression-like phenotypes in Chrna7 knock-out mice

A role of microRNA-149 in the prefrontal cortex for prophylactic actions of (R)-ketamine in inflammation model