Antidepressant drugs reverse the loss of adult neural stem cells following chronic stress

Abstract

In rodents, adult neurogenesis occurs in the olfactory bulb and the dentate gyrus of the hippocampus. It has been shown that exposure to psychosocial stress reduces cell proliferation in the dentate gyrus. However, little is known about how stress affects the proliferation kinetics of neural stem cells (NSCs) in the subventricular zone (SVZ), which provide new neurons to the olfactory bulb. We utilized a forced-swim model of stress in the mouse and found that chronic stress decreased the number of NSCs in the SVZ. The reduction of NSC number persisted for weeks after the cessation of stress but was reversed by treatment with the antidepressant drugs fluoxetine and imipramine. We demonstrated by in vitro colony-forming neurosphere assay that corticosterone attenuated neurosphere formation by adult NSCs and, in contrast, that serotonin increased the survival of NSCs. In addition, serotonin expanded the size of the NSC pool in the SVZ when it was infused into the lateral ventricle in vivo. These results suggest that, under chronic stress conditions, the number of NSCs is regulated by the actions of glucocorticoids and serotonin. These data provide insights into the molecular mechanisms underlying the pharmacological actions of antidepressant drugs.

The Clinical Features in Subarachnoid Hemorrhage of Unknown Etiology

“…We also see functional recovery, which correlates well with what is being seen in clinical trials of the drug in stroke patients [2,20] or traumatic brain injury patients [21]. Since stress has an inhibitory effect on neurogenesis and fluoxetine generally has a positive effect [22,23], we believe that care must be taken to eliminate stress when administering the fluoxetine to animal models of disease, which our drug delivery system accomplishes [8].…”

Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain

“…Other 5-HT receptors have been implicated in neurogenesis, including 5-HT1B, 5-HT2A, 5-HT2C and 5-HT4 (Banasr et al, 2004;Lucas et al, 2007; Jha et al, 2008). Nevertheless, there remains some controversy surrounding the expression pattern of these receptors in the neurogenic zones (Councill et al, 2006;Hitoshi et al, 2007). …”

From progenitors to integrated neurons: Role of neurotransmitters in adult olfactory neurogenesis

“…Decreased cell proliferation in the SVZ of bulbectomized rats is restored by imipramine, an inhibitor of 5-HT reuptake (Keilhoff et al, 2006). Similarly, antidepressant drugs have been also reported to reverse the loss of adult neural stem cells in the SVZ following chronic stress both in vitro and in vivo (Hitoshi et al, 2007) supporting that various components of the limbic system may exhibit alterations that can be reversed by monoaminergic antidepressants. Although progresses have been made in understanding serotonin role and regulation in SVZ adult neurogenesis, many questions remain still unsolved; i.e.…”

“…Although pharmacological in vivo and in vitro studies demonstrate that different families of 5-HT receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , 5-HT 2C ) are involved in the regulation of adult neurogenesis, their cellular localization in the SVZ is largely unknown. In vitro neurosphere cultures mainly composed of C-type cells, express only the 5-HT 2A receptor (Hitoshi et al, 2007). Transgenic mice expressing green fluorescent protein (GFP) under the promoter of 5-HT 3A receptor, as well as in situ hybridization data, show high expression of 5-HT 3A receptor on SVZ neuroblasts (Inta et al, 2008).…”