NPY augments the proliferative effect of FGF2 and increases the expression of FGFR1 on nestin positive postnatal hippocampal precursor cells, via the Y1 receptor

Abstract

1These authors contributed equally to this study.Abbreviations used:BrdU, bromodeoxyuridine; cDNA, complementary DNA; EGF, epidermal growth factor; FGF, fibroblast growth factor; FGFR, FGF receptor; NPY, neuropeptide YNSC, neural stem cell; NSPC, neural stem progenitor cell; SGZ, subgranular zone. AbstractWe have shown that neuropeptide Y (NPY), a peptide neurotransmitter released by hippocampal interneurons, is proliferative for hippocampal neural stem progenitor cells (NSPCs) via the Y1 receptor. Fibroblast growth factor (FGF) 2, released predominantly by astrocytes, is also a powerful mitogen for postnatal and adult NSPCs, via the FGFR1 receptor. Knockout studies show that NPY and FGF2 are individually necessary, but not sufficient, for seizure-induced neurogenesis, suggesting a possible interaction. Here, we examined for interactions between NPY and FGF2 on NSPCs from the postnatal hippocampus and report that the combination of NPY and FGF2 significantly shortens the cell cycle time of nestin positive NSPCs, more than either factor alone. This augmentation of proliferation rate is NPY Y1 receptor mediated, and Y1 receptor activation increases both FGFR1 mRNA and protein in NSPC cultures. NSPCs immunostain for both Y1 and FGFR1 receptors and the interaction is specific for dentate NSPCs. This is the first report of a proliferative factor that augments the proliferative effect of FGF2 and is the first evidence of a positive proliferative interaction between a glial growth factor and a neuronal transmitter, identifying a novel neural activity driven mechanism for modulating the proliferation of hippocampal NSPCs.

Differential Susceptibility of Interneurons Expressing Neuropeptide Y or Parvalbumin in the Aged Hippocampus to Acute Seizure Activity

“…This is supported by many previous observations, which comprise an increased hippocampal NPY expression in response to status epilepticus in young adult rats as a compensatory means to reduce seizures [32], [44], [45], seizure activity in response to reduced levels of NPY [45], and a reduced epileptiform-like activity with the administration of NPY in animal models of epilepsy [46]–[49]. Third, NPY has a role in the hippocampal neurogenesis and functions such as learning, memory and mood, as it enhances the proliferation of neural stem cells and augments the mitogenic effect of the fibroblast growth factor-2 on neural stem cells [31], [32], [50].…”

NPY promotes chemokinesis and neurogenesis in the rat subventricular zone

“…2009). Analyzing the contribution of NPY and its interplay with growth factors (Rodrigo et al. 2010) to the control of neurogenic activity under physiological and pathological conditions warrants further investigations.…”

Neuropeptide Y system in the retina: From localization to function

“…In an in vivo study, we also found that NPY protects rat retinal cells against apoptotic cell death and ganglion cell degeneration induced by intravitreal injection of glutamate (Santos-Carvalho et al, 2013b) . 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 In the CNS, NPY induces neuronal cell proliferation and differentiation, through the activation of NPY Y 1 receptors (Agasse et al, 2008;Decressac et al, 2011;Hansel et al, 2001;Howell et al, 2003;Rodrigo et al, 2010;Stanic et al, 2008) or NPY Y 2 receptors (Decressac et al, 2011;Stanic et al, 2008). The potency of these NPY effects is comparable to several trophic/growth factors, such as ciliary neurotrophic factor, vascular endothelial growth factor, and transforming growth factor (Decressac et al, 2011;Emsley and Hagg, 2003;Jin et al, 2002).…”