Prolactin Stimulates Precursor Cells in the Adult Mouse Hippocampus

Abstract

In the search for ways to combat degenerative neurological disorders, neurogenesis-stimulating factors are proving to be a promising area of research. In this study, we show that the hormonal factor prolactin (PRL) can activate a pool of latent precursor cells in the adult mouse hippocampus. Using an in vitro neurosphere assay, we found that the addition of exogenous PRL to primary adult hippocampal cells resulted in an approximate 50% increase in neurosphere number. In addition, direct infusion of PRL into the adult dentate gyrus also resulted in a significant increase in neurosphere number. Together these data indicate that exogenous PRL can increase hippocampal precursor numbers both in vitro and in vivo. Conversely, PRL null mice showed a significant reduction (approximately 80%) in the number of hippocampal-derived neurospheres. Interestingly, no deficit in precursor proliferation was observed in vivo, indicating that in this situation other niche factors can compensate for a loss in PRL. The PRL loss resulted in learning and memory deficits in the PRL null mice, as indicated by significant deficits in the standard behavioral tests requiring input from the hippocampus. This behavioral deficit was rescued by direct infusion of recombinant PRL into the hippocampus, indicating that a lack of PRL in the adult mouse hippocampus can be correlated with impaired learning and memory.

Altered immune pathway activity under exercise challenge in Gulf War Illness: An exploratory analysis

“…This role would be consistent with the down-regulation of death signaling found in our current analysis as well as recent evidence pointing to HPA axis dysfunction in these subjects, potentially involving altered pituitary function (Golier et al, 2007(Golier et al, , 2009. Finally the role of PRL in mediating neurogenesis (Walker et al, 2012), astrocyte proliferation and associated IL-1a production (DeVito et al, 1995) may explain at least in part the elevated PRL levels found in autoimmune illnesses like systemic lupus erythematosus (SLE) and multiple sclerosis (MS) (Shelly et al, 2012). More importantly, this role might offer a tentative mechanistic basis supporting the association of GWI severity with PRL/NF-jB and neurogenic pathway activation, via IL-10 and IL-1a in particular.…”

“…T and NK cell abundance (Walsh et al, 2011), IL-1a (Kimura et al, 2001), IL10, prolactin release (Rojas Vega et al, 2012) as well as neurogenic (Walker et al, 2012) and NF-jB activation (Kim et al, 2009), it is important to remember that they were selected on the basis of changes in symptom severity and pathway activation across subject groups. As a result we found some aspects of normal exercise response to be over-expressed or expressed earlier than normal in GWI.…”

One Mouse, Two Cultures: Isolation and Culture of Adult Neural Stem Cells from the Two Neurogenic Zones of Individual Mice

“…The precursor cells in the DG are activated by specific types of spatial learning and by stimuli such as environmental enrichment and physical activity, whereas the SVZ precursor cells are activated by olfactory learning and olfactory enrichment. Consistent with this, one of us (TLW) previously demonstrated that the DG contains a population of latent stem and progenitor cells that can be activated by neural excitation [15][16][17][18] . In contrast, we found that the SVZ precursor cells respond quite differently to this stimulus, with a decrease in neurosphere number in response to depolarizing levels of KCl 17.…”

The role of sex and sex-related hormones in cognition, mood and well-being in older men and women

“…Henry and Sherwin (2012) report that higher PRL levels had a detrimental effect in executive functioning, as we also observe here. In accordance, in animal studies, reduced PRL levels in mice seem to compromise learning and memory behaviors that require input from the hippocampus (Walker et al, 2012), and in male rats hyperprolactinemia impairs object recognition (Torner, Tinajero, Lajud, Quintanar-Stephano, & Olvera-Cortes (2013)). The reason why we could only verify these relationships in males (across all dimensions) remains to be explored, particularly as an association between hyperprolactinemia and increased levels of depression, anxiety and decreased libido has been reported in women (Lisansky et al, 1984).…”