Neuropeptide Y stimulates neuronal precursor proliferation in the post‐natal and adult dentate gyrus

Abstract

Adult dentate neurogenesis is important for certain types of hippocampal-dependent learning and also appears to be important for the maintenance of normal mood and the behavioural effects of antidepressants. Neuropeptide Y (NPY), a peptide neurotransmitter released by interneurons in the dentate gyrus, has important effects on mood, anxiety-related behaviour and learning and memory. We report that adult NPY Y -/-1 receptor knock-out mice have significantly reduced cell proliferation and significantly fewer immature doublecortinpositive neurons in the dentate gyrus. We also show that the neuroproliferative effect of NPY is dentate specific, is Y 1 -receptor mediated and involves extracellular signal-regulated kinase (ERK)1/2 activation. NPY did not exhibit any effect on cell survival in vitro but constitutive loss of the Y 1 receptor in vivo resulted in greater survival of newly generated neurons and an unchanged total number of dentate granule cells. These results show that NPY stimulates neuronal precursor proliferation in the dentate gyrus and suggest that NPYreleasing interneurons may modulate dentate neurogenesis.

IGF‐1 receptor‐mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus

“…Interestingly, the basal level of proliferation was not affected by U0126 microinfusion, indicating that the MAPK pathway is not required for constitutive cell division. This observation is similar to a recent report by Howell et al (2005) showing that neuropeptide Y (NPY)-mediated MAPK pathway activity blocked inducible but not the basal level of proliferation. With respect to inducible proliferation, our data are consistent with a number of recent studies implicating MAPK signaling in progenitor cell proliferation.…”

Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

“…3A). Furthermore, when examining NPY-induced ERK signaling pathway as reported previously [14,16,19,34], NPY failed to activate activity-related site-specific phosphorylation of ERK (Thr202/Tyr204) in isolated adipocytes while NE stimulated it (Fig. 3B).…”

“…NPY has been shown to activate ERK pathway in a variety of cells, possibly leading to cell proliferation of neuronal precursor cells [14,16] and progression of cancer [34]. Moreover, Yang et al…”

Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity

“…Investigation of olfactory neuronal precursor cells in mice with a targeted deletion of NPY revealed a reduction in neuronal precursor proliferation resulting in fewer olfactory neurons (42) and indicated that NPY is required for the normal proliferation of olfactory neurospheres in vitro. (43) Similarly, NPY has been shown in mice to promote the proliferation of neuronal progenitor cells in the dentate gyrus of the hippocampus (28,44) and also in the subventricular zone. (45,46) Interestingly, in all cases, the Y receptor mediating these effects is the Y1 receptor.…”