The relationships between depression and gut microbiota, particularly those involving the immune system, have become a major focus of recent research. Here, we analyzed changes in gut microbiota and their sulfur metabolites in the feces of a depression rat model using the modified 14-day social defeat stress (SDS) paradigm. Our results showed that SDS increased fecal Lactobacillus reuteri in correlation with ergothioneine levels at around day 11, which continued for at least 1 month following SDS administration. In vitro study further revealed that L. reuteri is capable of producing ergothioneine. Although the known anti-inflammatory and anti-oxidative actions of ergothioneine suggested that the increased fecal ergothioneine levels may be related to intestinal anti-inflammatory defense mechanisms, no change was observed in the plasma ergothioneine levels during the same observation period, indicating that the defense mechanisms may not be sufficiently reflected in the body. As ergothioneine is a natural ingredient that is absorbed mainly from the upper gastrointestinal tract, we hypothesized that oral ergothioneine may exert antidepressant effects. As expected, oral administration of ergothioneine prior to and during the SDS paradigm had a preventative effect on SDS-induced depressive behaviors, such as social avoidance and depression-like sleep abnormalities, particularly those of rapid eye movement sleep. These findings indicate that ergothioneine, a metabolite of L. reuteri, may be a common substance in the microbiota-gut-brain axis that prevents stress-induced sleep disturbances, especially those associated with depression. Recent research has reported the influence of gut microbiota on cerebral function (i.e., the microbiota-gutbrain axis) 4-9. For example, depressive behaviors develop in germ-free rodents following fecal transplants from human patients with MDD 10,11. On the other hand, decreases in MDD-like behaviors occurred following the administration of prebiotics in mice subjected to mild

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Genetic variations in the gene encoding dysbindin has consistently been associated with schizophrenia and bipolar disorder, although little is known about the neural functions carried out by dysbindin. To gain some insight into this area, we took advantage of the readily available dysbindin-null mouse sandy (sdy−/−) and studied hippocampal neurogenesis using thymidine analogue bromodeoxuridine (BrdU). No significant differences were found in the proliferation (4 hours) or survival (1, 4 and 8 weeks after the last BrdU injection) of progenitors in the subgranular regions of the dentate gyrus between sdy−/− and sdy+/+ (control) mice. However, 4 weeks after the last BrdU injection, a significant reduction was observed in the ratio of neuronal differentiation in sdy−/− when compared to that of sdy+/+ (sdy+/+  = 87.0±5.3% vs. sdy−/−  = 71.3±8.3%, p = 0.01). These findings suggest that dysbindin plays a role during differentiation process in the adult hippocampal neurogenesis and that its deficit may negatively affect neurogenesis-related functions such as cognition and mood.

Although It is widely recognized that virtually all antidepressants (ADs) suppress rapid eye movement (REM) sleep, the effects of chronic AD treatments on sleep abnormalities, especially those of REM sleep, have rarely been investigated comprehensively in animal models of major depressive disorder (MDD). Here, we show that chronic social defeat stress (SDS) in rats induces prolonged social avoidance and MDD-like alterations in sleep architecture (increased REM sleep durations, bouts, and shortened REM latency) even a month after the last SDS. These abnormalities were associated with changes in electroencephalography (EEG) spectra powers, such as reduced REM sleep theta powers during the light phase. Chronic AD treatments significantly ameliorated these behavioral, sleep, and EEG abnormalities, although in some cases not to control levels. Interestingly, the social interaction ratios a month after the last SDS most strongly correlated with the REM sleep theta powers. These results suggest that chronic AD treatments suppress REM sleep durations and bouts as observed in human MDD patients, but, at the same time, increase REM sleep theta power. The latter is an EEG parameter that has never been directly investigated in humans, and which may be responsible for the therapeutic effects of ADs.3 Significance StatementDisturbed sleep is one of nine diagnostic criteria for major depressive disorder (MDD), which usually resolves with adequate treatment. However, little is known about how antidepressants (AD) work in MDD animal models. Here, we developed a novel rat social defeat stress model demonstrating long-lasting MDD-like sleep disturbances. We found that chronic AD treatments suppressed REM durations and bouts as reported previously, but, at the same time, increased REM sleep theta power. Interestingly, among several sleep parameters, only REM sleep theta power strongly correlated with depressive symptoms at 1M. Thus, REM sleep theta power, an EEG parameter that has never been investigated directly in humans, could be a novel indicator for MDD and/or AD effects.

To characterize the deficit in random number generation in schizophrenia with respect to control of sensory information processing, the present study employed a random number generation task using 10 digits (0 to 9) and compared two response modes (oral and written) with different amounts of sensory availability about the previous choices of the subject. Analysis indicated that the increased availability of previous information in the written response mode may exacerbate an aspect of the deficit in random number generation in schizophrenia reflecting the disturbance in control of sensory information processing. The comparison of performance in written and oral response modes may be useful in assessing schizophrenic psychopathology.