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The effects of chronic antidepressant (AD) treatment on sleep disturbances in rodent chronic stress models have not been thoroughly investigated. Here, we show that chronic social defeat stress (SDS) in rats induces prolonged social avoidance, alterations in sleep architecture (increased total rapid eye movement [REM] sleep duration, bout, and shortened REM latency), and contextual but not cued fear memory deficits, even 1 month after the last SDS. These abnormalities were associated with changes in electroencephalography (EEG) spectral powers, including reduced REM sleep theta power during the light phase. Chronic treatment with two different classes of antidepressants (ADs), imipramine and fluoxetine, significantly ameliorated these behavioral, sleep, and EEG abnormalities. Interestingly, REM theta power was normalized by chronic (1 month) but not 1 week AD administration and solely correlated with the ratio (an objective indicator) of social interaction 1 month after the last SDS. These data suggest that reductions in REM sleep theta power, an EEG parameter that has never been directly investigated in humans, is a core sleep symptom in socially defeated rats, and, potentially, also in patients with stress-related psychiatric disorders, including major depressive and posttraumatic stress disorders.

The role of oligodendrocyte lineage cells, the largest glial population in the adult central nervous system (CNS), in the pathogenesis of Alzheimer’s disease (AD) remains elusive. Here, we developed a culture method for adult oligodendrocyte progenitor cells (aOPCs). Fibroblast growth factor 2 (FGF2) promotes survival and proliferation of NG2+ aOPCs in a serum-free defined medium; a subpopulation (~5%) of plexin-B3+ aOPCs was also found. FGF2 withdrawal decreased NG2+, but increased plexin-B3+ aOPCs and Aβ1-42 secretion. Plexin-B3+ aOPCs were distributed throughout the adult rat brain, although less densely than NG2+ aOPCs. Spreading depolarization induced delayed cortical plexin-B3+ aOPC gliosis in the ipsilateral remote cortex. Furthermore, extracellular Aβ1-42 accumulation was occasionally found around plexin-B3+ aOPCs near the lesions. In AD brains, virtually all cortical SPs were immunostained for plexin-B3, and plexin-B3 levels increased significantly in the Sarkosyl-soluble fractions. These findings suggest that plexin-B3+ aOPCs may play essential roles in AD pathogenesis, as natural Aβ-secreting cells., In order to investigate the role of oligodendrocyte lineage cells in Alzheimer’s Disease (AD) pathology, Nihonmatsu-Kikuchi et al developed a culture method for adult oligodendrocyte progenitor cells in the rat. Using this method as well as imaging AD patient brain tissue, they found that plexin-B3-expressing cells could be a potential source of amyloid β peptide.

The roles played by oligodendrocyte (OL) lineage cells, the largest glial population in the adult CNS, in the pathogenesis of Alzheimer’s 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 β peptides (Aβ)-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, Aβ1-40, −42 secretions and Aβ1-42/total Aβ 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 Aβ source.

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.

The role of oligodendrocyte lineage cells, the largest glial population in the adult central nervous system (CNS), in the pathogenesis of Alzheimer's disease (AD) remains elusive. Here, we developed a culture method for adult oligodendrocyte progenitor cells (aOPCs). Fibroblast growth factor 2 (FGF2) promotes survival and proliferation of NG2