Neuropeptide Y is important for basal and seizure-induced precursor cell proliferation in the hippocampus

Howell, Owain W.; Silva, Sharmalene; Scharfman, Helen E.; Sosunov, Alexander A.; Zaben, Malik; Shatya, Anan; McKhann, Guy M.; Herzog, Herbert; Laskowski, Alexandra; Gray, William Peter

doi:10.1016/j.nbd.2006.12.014

Cited by 99 publications

(107 citation statements)

References 60 publications

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“…Mice with targeted deletion of NPY (8) contain half as many dividing olfactory neuronal precursor cells as normal and fewer olfactory neurons by adulthood (9), likely mediated through the Y1 receptor (R) subtype (9, 10). This is supported by in vivo work showing that the dentate gyrus of mice lacking Y1Rs has significantly reduced cell proliferation and fewer immature neurons (11,12). Our recent observation of strong Y2R protein expression in a tract immediately alongside the RMS (13) also suggests a possible role for this receptor.…”

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confidence: 58%

“…Y1R-mediated regulation of cell proliferation has also been reported in the dentate SGZ of 35-day-old mice lacking Y1Rs, where 40% fewer cells than normal incorporated BrdU (11,12). Such Y1R-mediated proliferative effects of NPY require activation of the extracellular signal-regulated kinase (ERK1/2) subgroup of mitogenactivated protein kinases and protein kinase C (9, 11), which have been implicated in proliferation of neural progenitors (22).…”

Section: Discussionmentioning

confidence: 93%

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Peptidergic influences on proliferation, migration, and placement of neural progenitors in the adult mouse forebrain

Stanić

Paratcha

Ledda

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Neural progenitor proliferation, differentiation, and migration are continually ongoing processes in the subventricular zone (SVZ) and rostral migratory stream (RMS) of the adult brain. There is evidence that peptidergic systems may be involved in the molecular cascades regulating these neurogenic processes, and we examined a possible influence of neuropeptide Y (NPY) and cholecystokinin (CCK) systems in cell proliferation and neuroblast formation in the SVZ and RMS and generation of interneurons in the olfactory bulb (OB). We show that NPY and the Y1 and Y2 receptor (R) proteins are expressed in and surrounding the SVZ and RMS and that Y1R is located on neuroblasts in the anterior RMS. Mice deficient in Y1Rs or Y2Rs have fewer Ki-67-immunoreactive (ir) proliferating precursor cells and doublecortin-ir neuroblasts in the SVZ and RMS than WT mice, and less calbindin-, calretinin-, and tyrosine hydroxylase-ir interneurons in the OB. Mice lacking CCK1Rs have fewer proliferating cells and neuroblasts than normal and a shortage of interneurons in the OB. These findings suggest that both NPY and CCK through their receptors help to regulate the proliferation of precursor cells, the amount of neuroblast cells in the SVZ and RMS, and influence the differentiation of OB interneurons.adult neurogenesis ͉ CCK receptors ͉ neuropeptides ͉ NPY receptors ͉ rostral migratory stream T he mature mammalian nervous system arises from precisely coordinated proliferation, differentiation, and migration of precursor cells during embryonic and early postnatal development (1). In adulthood, neurogenesis is restricted to three regions: the subventricular or subependymal zone (SVZ) of the lateral ventricle, the olfactory bulb (OB), and in the subgranular zone (SGZ) of the dentate gyrus. In the adult, newborn cells in the SGZ (2) integrate into hippocampal circuitry and are associated with learning and memory formation (3), whereas neural progenitor cells in the SVZ migrate along the rostral migratory stream (RMS) to the center of the OB, where they radiate to become interneurons in granule, periglomerular, and external plexiform cell layers (4, 5).Cascades of molecular signals that underlie fate specification and migration of adult neural progenitors have begun to be clarified (6, 7), and peptidergic systems also appear to participate in these processes. Neuropeptide Y (NPY), which is widely expressed in the central and peripheral nervous system during development and adulthood, has been implicated in proliferation of neuronal precursor cells in olfactory regions and the SGZ. Mice with targeted deletion of NPY (8) contain half as many dividing olfactory neuronal precursor cells as normal and fewer olfactory neurons by adulthood (9), likely mediated through the Y1 receptor (R) subtype (9, 10). This is supported by in vivo work showing that the dentate gyrus of mice lacking Y1Rs has significantly reduced cell proliferation and fewer immature neurons (11,12). Our recent observation of strong Y2R protein expression in a tract immediately along...

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confidence: 58%

Section: Discussionmentioning

confidence: 93%

Peptidergic influences on proliferation, migration, and placement of neural progenitors in the adult mouse forebrain

Stanić

Paratcha

Ledda

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…(2) Several reports indicate that mechanisms of action of antidepressants could involve hippocampal NPY (Caberlotto et al, 1998;Mathé et al, 1997). (3) In the hippocampus, in vitro studies have shown that NPY exerts a neuroproliferative effect on neuronal precursors proliferation (Decressac et al, 2010;Howell et al, 2007).…”

Section: Ria Assay Of Npymentioning

confidence: 99%

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

Cohen

Liu

Kozlovsky

et al. 2011

Neuropsychopharmacol

235

190

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Converging evidence implicates the regulatory neuropeptide Y (NPY) in anxiety-and depression-related behaviors. The present study sought to assess whether there is an association between the magnitude of behavioral responses to stress and patterns of NPY in selected brain areas, and subsequently, whether pharmacological manipulations of NPY levels affect behavior in an animal model of PTSD. Animals were exposed to predator-scent stress for 15 min. Behaviors were assessed with the elevated plus maze and acoustic startle response tests 7 days later. Preset cutoff criteria classified exposed animals according to their individual behavioral responses. NPY protein levels were assessed in specific brain regions 8 days after the exposure. The behavioral effects of NPY agonist, NPY-Y1-receptor antagonist, or placebo administered centrally 1 h post-exposure were evaluated in the same manner. Immunohistochemical technique was used to detect the expression of the NPY, NPY-Y1 receptor, brain-derived neurotrophic factor, and GR 1 day after the behavioral tests. Animals whose behavior was extremely disrupted (EBR) selectively displayed significant downregulation of NPY in the hippocampus, periaqueductal gray, and amygdala, compared with animals whose behavior was minimally (MBR) or partially (PBR) disrupted, and with unexposed controls. One-hour post-exposure treatment with NPY significantly reduced prevalence rates of EBR and reduced trauma-cue freezing responses, compared with vehicle controls. The distinctive pattern of NPY downregulation that correlated with EBR as well as the resounding behavioral effects of pharmacological manipulation of NPY indicates an intimate association between NPY and behavioral responses to stress, and potentially between molecular and psychopathological processes, which underlie the observed changes in behavior. The protective qualities attributed to NPY are supported by the extreme reduction of its expression in animals severely affected by the stressor and imply a role in promoting resilience and/or recovery.

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“…Hippocampal NPY may thus serve a neuroprotective role during conditions of cellular stress, but at the same time inhibit neuroplasticity relevant to learning. Finally, NPY produces a strong neuroproliferative effect in the dentate gyrus (Howell et al, 2005;Howell et al, 2007), which may represent a line of defense against the suppression of neurogenesis seen in sleep loss (GuzmanMarin et al, 2003). Further studies are needed to test these possibilities.…”

Section: Sleep Deprivation Npy Expression and Hippocampal Plasticitymentioning

confidence: 99%

Upregulation of Gene Expression in Reward-Modulatory Striatal Opioid Systems by Sleep Loss

Baldo

Hanlon

Obermeyer

et al. 2013

Neuropsychopharmacol

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Epidemiological studies have shown a link between sleep loss and the obesity 'epidemic,' and several observations indicate that sleep curtailment engenders positive energy balance via increased palatable-food 'snacking.' These effects suggest alterations in rewardmodulatory brain systems. We explored the effects of 10 days of sleep deprivation in rats on the expression of striatal opioid peptide (OP) genes that subserve food motivation and hedonic reward, and compared effects with those seen in hypothalamic energy balanceregulatory systems. Sleep-deprived (Sleep-Dep) rats were compared with yoked forced-locomotion apparatus controls (App-Controls), food-restricted rats (Food-Restrict), and unmanipulated controls (Home-Cage). Detection of mRNA levels with in situ hybridization revealed a subregion-specific upregulation of striatal preproenkephalin and prodynorhin gene expression in the Sleep-Dep group relative to all other groups. Neuropeptide Y (NPY) gene expression in the hippocampal dentate gyrus and throughout neocortex was also robustly upregulated selectively in the Sleep-Dep group. In contrast, parallel gene expression changes were observed in the Sleep-Dep and Food-Restrict groups in hypothalamic energy-sensing systems (arcuate nucleus NPY was upregulated, and cocaine-and amphetamine-regulated transcript was downregulated), in alignment with leptin suppression in both groups. Together, these results reveal a novel set of sleep deprivation-induced transcriptional changes in reward-modulatory peptide systems, which are dissociable from the energy-balance perturbations of sleep loss or the potentially stressful effects of the forced-locomotion procedure. The recruitment of telencephalic food-reward systems may provide a feeding drive highly resistant to feedback control, which could engender obesity through the enhancement of palatable feeding.

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Neuropeptide Y is important for basal and seizure-induced precursor cell proliferation in the hippocampus

Cited by 99 publications

References 60 publications

Peptidergic influences on proliferation, migration, and placement of neural progenitors in the adult mouse forebrain

Peptidergic influences on proliferation, migration, and placement of neural progenitors in the adult mouse forebrain

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

Upregulation of Gene Expression in Reward-Modulatory Striatal Opioid Systems by Sleep Loss

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