Neuropeptide Y promotes neurogenesis and protection against methamphetamine-induced toxicity in mouse dentate gyrus-derived neurosphere cultures

Baptista, Sofia; Bento, Ana Rita; Gonçalves, Joana; Bernardino, Liliana; Summavielle, Teresa; Lobo, Andrea; Ribeiro, Carlos; Malva, João O.; Agasse, Fabienne; Silva, Ana P.

doi:10.1016/j.neuropharm.2012.02.015

Cited by 42 publications

(31 citation statements)

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“…In vitro studies also point that METH reduced proliferation of rat hippocampal neural progenitor cells (Tian et al, 2009;Venkatesan et al, 2011). Additionally, our group recently verified that a nontoxic concentration of METH (1 nM for 7 days) decreased the number of mature neurons in DG-derived neurosphere cultures (Baptista et al, 2012). Concerning the subventricular zone (SVZ), we have also shown that METH decreases cell proliferation, neuronal differentiation and maturation of stem/progenitor cells (Bento et al, 2011).…”

Section: Introductionmentioning

confidence: 66%

“…Cells were adhered to SuperFrost Plus glass slides (Thermo Scientific, Menzel GmbH & Co. KG, Braunschweig, Germany) by centrifugation (360 ×g, 5 min; Cellspin I, Tharmac GmbH, Waldsolms, Germany), and fixed in 4% paraformaldehyde (PFA). Afterwards, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was performed to label apoptotic nuclei, as previously described by us (Baptista et al, 2012). Briefly, cells were rinsed 3× for 10 min with 0.01 M phosphatebuffered saline (PBS) and permeabilized in 0.25% Triton X-100 for 30 min at room temperature.…”

Section: Dentate Gyrus Neurosphere Culturesmentioning

confidence: 99%

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Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

et al. 2014

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Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse that negatively interferes with neurogenesis. In fact, we have previously shown that METH triggers stem/progenitor cell death and decreases neuronal differentiation in the dentate gyrus (DG). Still, little is known regarding its effect on DG stem cell properties. Herein, we investigate the impact of METH on mice DG stem/progenitor cell self-renewal functions. METH (10nM) decreased DG stem cell self-renewal, while 1nM delayed cell cycle in the G0/G1-to-S phase transition and increased the number of quiescent cells (G0 phase), which correlated with a decrease in cyclin E, pEGFR and pERK1/2 protein levels. Importantly, both drug concentrations (1 or 10nM) did not induce cell death. In accordance with the impairment of self-renewal capacity, METH (10nM) decreased Sox2(+)/Sox2(+) while increased Sox2(-)/Sox2(-) pairs of daughter cells. This effect relied on N-methyl-d-aspartate (NMDA) signaling, which was prevented by the NMDA receptor antagonist, MK-801 (10μM). Moreover, METH (10nM) increased doublecortin (DCX) protein levels consistent with neuronal differentiation. In conclusion, METH alters DG stem cell properties by delaying cell cycle and decreasing self-renewal capacities, mechanisms that may contribute to DG neurogenesis impairment followed by cognitive deficits verified in METH consumers.

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Section: Introductionmentioning

confidence: 66%

Section: Dentate Gyrus Neurosphere Culturesmentioning

confidence: 99%

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

et al. 2014

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“…It has been previously reported that NPY promotes self-renewal of neural progenitor cells in the subgranular zone of the dentate gyrus (61); however, it only induces neuronal differentiation in the subventricular zone where it fails to promote self-renewal (62,63). In fact, previous reports have shown that the increase in proliferation in the subgranular zone is through the NPY R1 receptor via the ERK pathway (58,64,65); a receptor that we show in this report is activated by our recombinant NPY-apoB consistent with these previous findings. Although we did not investigate the subventricular zone in this study due its relevance to AD, it would be interesting to examine it in the future.…”

Section: Discussionmentioning

confidence: 98%

Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease

Spencer¹,

Potkar²,

Metcalf

et al. 2016

Journal of Biological Chemistry

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Neuropeptide Y (NPY) is one of the most abundant protein transmitters in the central nervous system with roles in a variety of biological functions including: food intake, cardiovascular regulation, cognition, seizure activity, circadian rhythms, and neurogenesis. Reduced NPY and NPY receptor expression is associated with numerous neurodegenerative disorders including Alzheimer disease (AD). To determine whether replacement of NPY could ameliorate some of the neurodegenerative and behavioral pathology associated with AD, we generated a lentiviral vector expressing NPY fused to a brain transport peptide (apoB) for widespread CNS delivery in an APP-transgenic (tg) mouse model of AD. The recombinant NPY-apoB effectively reversed neurodegenerative pathology and behavioral deficits although it had no effect on accumulation of A␤. The subgranular zone of the hippocampus showed a significant increase in proliferation of neural precursor cells without further differentiation into neurons. The neuroprotective and neurogenic effects of NPY-apoB appeared to involve signaling via ERK and Akt through the NPY R1 and NPY R2 receptors. Thus, widespread CNS-targeted delivery of NPY appears to be effective at reversing the neuronal and glial pathology associated with A␤ accumulation while also increasing NPC proliferation. Overall, increased delivery of NPY to the CNS for AD might be an effective therapy especially if combined with an anti-A␤ therapeutic.Neuropeptide Y (NPY), 2 one of the most abundant neuropeptides in the central and peripheral nervous system is synthesized in neurons and transported to pre-and post-synaptic vesicles where it is secreted (1). NPY is produced as preproenzyme that is processed first by removal of the secretory signal in the endoplasmic reticulum to produce the pro-NPY and then by the peptidase convertase to generate NPY(1-39). Further editing by peptidase enzymes generates the mature NPY(1-36) (2).This mature form binds primarily to three different receptors in the rodent brain, NPY R1, NPY R2, and NPY R5; which are all seven transmembrane receptors (3). Upon binding to the receptor, signaling pathways involve the activation of the G i /G o receptors and inhibition of cAMP synthesis followed by signaling through protein kinase C, mitogen-activated protein kinase (MAPK), inositol trisphosphate, and extracellular signal related kinase (ERK) (3).NPY is associated with a variety of biologic functions including: food intake, cardiovascular regulation, cognition, seizure activity, circadian rhythms, and neurogenesis (4). Alterations in NPY have been associated with many neurodegenerative disorders including Downs syndrome (5), Huntington disease (6), and epilepsy (1), and reduced NPY levels have been reported in the CNS in Alzheimer disease (AD). Immunocytochemical studies have shown decreased NPY (7-12) and NPY receptors (13) immunoreactivity in the hippocampus of AD patients and NPY accumulation in dystrophic neurites around the amyloid plaques (14). In addition, reduced levels of NPY in the plasma (1...

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“…95,97,98 In contrast, we have shown that NPY has a protective role against 3,4-methylenedioxy-N-methylamphetamine (MDMA)-induced toxicity in rat retinal cells. 31 86 Western blot analysis of rat hippocampus, rat whole brain, and dentate gyrus neurospherederived cultures reveals a 50 kDa single band. 86 The preabsortion control has shown no immunostaining.…”

Section: Discussionmentioning

confidence: 99%

“…31 86 Western blot analysis of rat hippocampus, rat whole brain, and dentate gyrus neurospherederived cultures reveals a 50 kDa single band. 86 The preabsortion control has shown no immunostaining.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y Receptors Y₁and Y₂are Present in Neurons and Glial Cells in Rat Retinal Cells in Culture

Santos-Carvalho

Aveleira²,

Elvas

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous system (CNS), including the retina. This peptide activates various different G-coupled receptors (NPY Y 1 , Y 2 , Y 4 , and Y 5 ) that are also present in the retina. However, the localization of NPY receptors in the several types of retinal cells is not completely known. In this study, we have looked at the distribution of NPY Y 1 and Y 2 receptors in rat retinal cells to reveal new perspectives on the role of NPY receptors in retina physiology. METHODS.Rat retinal neural cell cultures were prepared from newborn Wistar rats (P3-P5) and pure rat Müller cell culture was obtained after treatment of these cells with ascorbic acid. 1 This 36-amino acid peptide was first isolated from the pig brain in 1982 by Tatemoto.2 NPY is one of the most abundant peptides in the central nervous system (CNS), including the retina, and is involved in numerous physiologic functions, such as feeding, memory processing, and cognition.3,4 NPY actions are mediated by G protein-coupled receptors, which have been named NPY Y 1 , Y 2 , Y 4 , Y 5 , and y 6 . 3,5 NPY is expressed in the retina of mammals and nonmammals. [6][7][8][9][10][11][12] In rodent retinas, NPY-immunoreactivity (NPY-ir) is present in the inner retina, it is localized in cell bodies at both inner nuclear layer (INL) and ganglion cell layer (GCL), and is also present in processes located in the inner plexiform layer (IPL).11,13 NPY shows one of the highest degrees of phylogenetic preservation, compared with other neuropeptides, and does not show marked differences between species.14,16 From a consideration of the phylogenetic preservation, it is expected that the NPY and NPY receptor distribution in the retina does not vary significantly between species. NPY-ir is present in amacrine cells in the majority of species studied (fish, frogs, lizards, rodents, baboons, pigs, cats, chickens, and pigeons). Cats, dogs, dolphins, and humans also show NPY in their ganglion cells, 9,17-20 while some turtles, lizards, and frogs present NPY-ir in bipolar cells. 8,21,22 Few studies have analyzed the distribution of NPY receptors either in the retina or in specific retinal cell types. The presence of both Y 1 and Y 2 receptors in the mouse retina has been confirmed by mRNA analysis 13,23 ; however, it is unclear which cell types express these receptors. Moreover, in primary cultures of Müller cells isolated from the retina of guinea pig, a functional assay of cell proliferation suggested the presence of NPY Y 1 receptor in these glial cells. 24 In human retinal pigment epithelium (RPE), mRNA encoding for NPY Y 1 , Y 2 , and Y 5 receptors has been detected, while in bovine RPE only mRNAs encoding for NPY Y 1 and Y 2 receptors have been found. 25 Although the presence of NPY receptors in the rat retina has been described, in particular in NPY Y 1 , Y 2 , Y 4 , and Y 5 mRNA expression, 26,27 little is known about their localization. The NPY Y 1 receptor-ir is localized in horizontal and amacrine ce...

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Neuropeptide Y promotes neurogenesis and protection against methamphetamine-induced toxicity in mouse dentate gyrus-derived neurosphere cultures

Cited by 42 publications

References 74 publications

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease

Neuropeptide Y Receptors Y₁and Y₂are Present in Neurons and Glial Cells in Rat Retinal Cells in Culture

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Neuropeptide Y promotes neurogenesis and protection against methamphetamine-induced toxicity in mouse dentate gyrus-derived neurosphere cultures

Cited by 42 publications

References 74 publications

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease

Neuropeptide Y Receptors Y1and Y2are Present in Neurons and Glial Cells in Rat Retinal Cells in Culture

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Neuropeptide Y Receptors Y₁and Y₂are Present in Neurons and Glial Cells in Rat Retinal Cells in Culture