Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus

Abstract

Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus, and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.

Familial and environmental influences on brain volumes in twins with schizophrenia

“…22,47 It may be that the hippocampus is vulnerable to a variety of environmental factors, including obstetric complications 48 and stress, 49 varying according to the hormonal milieu 50 that is then linked to schizophrenia. 51 We confirmed our hypothesis of an association between low birth weight and hypoxia and smaller whole brain, white matter and grey matter volumes. It is accepted that perinatal obstetric complications have an effect on brain structure, function 52 and neurodevelopment.…”

Neuroprotective effects of Tualang honey against oxidative stress and memory decline in young and aged rats exposed to noise stress

“…Significant difference between stress control and stress treated with honey ( ♣ P < .05). both glucocorticoid exposure and oxidative stress may induce neuronal oxidative stress through enhanced mitochondrial respiration and oxidative phosphorylation [50], and promote gliogenesis over neurogenesis in hippocampal neural stem cell progenitors [51,52]. Correspondingly, we demonstrated that the stressed rats possessed a lower number of pyramidal neurons in the hippocampus as well as in the mPFC compared to the nonstressed rats.…”

Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors

“…A recent study has shown that acute CORT treatment (for 7 days) shifts the balance of cell types produced towards fewer neurons and more oligodendrocytes, and has suggested the possibility that this shift may underlie behavioral effects of CORT treatment (Chetty et al, 2014). We note that here we did not observe a significant effect of CORT treatment on the percent of BrdU-positive cells that are colabeled with the neuronal marker NeuN (Figure 3d), possibly because BrdU was injected 4 weeks before the onset of CORT treatment (Figure 3a).…”

“…While neurons make up the majority of adult-born cells labeled with BrdU in the hippocampus, stem cells, and astrocytes and potentially even oligodendrocytes (Chetty et al, 2014) are also found. To determine the proportion of neurons produced, colabeling was assessed between BrdU and the mature neuronal marker neuronal nuclei (NeuN).…”