Biology subjects

Ozawa, N.

Publications and source records attributed to Ozawa, N..

3 recordsLinked to original sources

bioRxiv2020

Essential roles of plexin-B3+ oligodendrocyte precursor cells in the pathogenesis of Alzheimer's disease

The roles played by oligodendrocyte (OL) lineage cells, the largest glial population in the adult CNS, in the pathogenesis of Alzheimers disease (AD) remain elusive. Here, we show a newly developed culture method for adult OL progenitor cells (aOPCs) and identify novel plexin-B3-expressing (plexin-B3+) aOPCs as potential amyloid {beta} peptides (A{beta})-secreting cells. Fibroblast growth factor 2 (FGF2) promotes the survival and proliferation of aOPCs in a serum-free defined medium. Although the whole expression profiles of the expanded aOPCs closely resemble those of in vivo OPCs, we found a subpopulation (up to 5%) of plexin-B3+/olig2+ aOPCs in the cultures growing in FGF2. FGF2 withdrawal decreased NG2+, but increased plexin-B3+ aOPCs with increased APP expression, A{beta}1-40, -42 secretions and A{beta}1-42/total A{beta} ratios in association with cored senile plaque-like morphological changes. In vivo, plexin-B3+ aOPCs are distributed throughout the adult brain, although less densely so than NG2+ aOPCs. Spreading depolarization, a type of brain injury, induced unique delayed cortical plexin-B3+ aOPC gliosis in the ipsilateral, but not in the contralateral, remote cortex. In AD brains, virtually all senile plaques in the cortex were immunostained with plexin-B3 antibodies and the levels of cortical plexin-B3 expression increased significantly in the Salcosyl-soluble fractions. These findings suggest that plexin-B3+ aOPCs play important roles in the pathogenesis of AD most likely as a natural A{beta} source.

neuroscience↗

bioRxiv2020

Ergothioneine, a metabolite of the gut bacterium Lactobacillus reuteri, protects against stress-induced sleep disturbances

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 one 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.

neuroscience↗

bioRxiv2020

Chronic antidepressant treatments rescue reduced REM sleep theta power in a rat social defeat stress model of depression

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. 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.

neuroscience↗