Physiology and gene regulation of the brain NPY Y1 receptor

Eva, Carola; Serra, Mariangela; Marrama, P; Panzica, Giancarlo; Oberto, Alessandra

doi:10.1016/j.yfrne.2006.07.002

Cited by 128 publications

(108 citation statements)

References 414 publications

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“…However, the VMN core is not devoid of NPY projections (Broberger et al, 1998;Fetissov et al, 2003) and NPY released in the shell would also be expected to diffuse into the core to affect neuronal activity. The postsynaptic site of NPY action within the VMN core is consistent with the strong expression there of Y 1 receptors (Kishi et al, 2005;Eva et al, 2006) and is also consistent with a previous report showing the Y 1 -mediated inhibition of VMN neurons (Kumarnsit et al, 2003). In addition, these experiments show the postsynaptic NPY response to be entirely Y 1 -mediated and provide insight into the abundance of NPY-sensitive neurons in the VMN.…”

Section: Npy Activates Postsynaptic Y 1 Receptors In the Vmnsupporting

confidence: 90%

Neuropeptide Y Suppresses Anorexigenic Output from the Ventromedial Nucleus of the Hypothalamus

Chee¹,

Myers²,

Price³

et al. 2010

J. Neurosci.

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Output from the hypothalamic ventromedial nucleus (VMN) is anorexigenic and is supported by the excitatory actions of leptin. The VMN is also highly sensitive to the orexigenic actions of Neuropeptide Y (NPY). We report that NPY robustly inhibits VMN neurons by hyperpolarizing them and decreasing their ability to fire action potentials. This action was mediated by Y 1 receptors coupled to the activation of GIRKs (G-protein-coupled inwardly rectifying potassium channels). Approximately 80% of VMN neurons expressing leptin receptors were sensitive to the actions of NPY, whereas 75% of NPY-sensitive neurons in VMN also responded to glucose by being uniformly inhibited by elevations in glucose. Interestingly, only ϳ36% of NPY-sensitive, leptin receptor b-expressing neurons were also glucosensitive. We suggest that NPY inhibits VMN neurons that are excited by leptin, thereby arresting the anorexigenic tone exerted by VMN neurons. The results further suggest a dynamic interplay between anorexigenic and orexigenic neuromodulators within the VMN to directly affect energy balance.

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Section: Npy Activates Postsynaptic Y 1 Receptors In the Vmnsupporting

confidence: 90%

Neuropeptide Y Suppresses Anorexigenic Output from the Ventromedial Nucleus of the Hypothalamus

Chee¹,

Myers²,

Price³

et al. 2010

J. Neurosci.

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“…where it is involved in the regulation of anxiety, stress reactions, energy balance, circadian rhythms, and cognition (1)(2)(3). Clinical studies suggest that NPY plays an important role in the response to stress and in psychiatric disorders (4).…”

Section: N Europeptide Y (Npy) Is Widely Distributed In the Cnsmentioning

confidence: 99%

“…Intracerebroventricular injection of NPY reduces both anxiety-and stress-related behavior in several animal models, an effect that is primarily mediated by Y1 receptors (Y1Rs) expressed in amygdala, hippocampus, and locus coeruleus (6)(7)(8)(9). The implications of a role of endogenous NPY in acting via Y1R to control emotionality, mood, and stress reactions have been probed with Y1R-selective antagonists and antisense oligonucleotides (1). NPY exerts its anxiolytic-like effect in the brain via interactions with the hypothalamic-pituitaryadrenocortical (HPA) axis and corticosteroids.…”

Section: N Europeptide Y (Npy) Is Widely Distributed In the Cnsmentioning

confidence: 99%

“…In addition to its crucial role in emotional behavior, NPY potently stimulates feeding, reduces energy expenditure, and induces obesity via the activation of Y1R expressed in the hypothalamus (1). However, global Npy1r gene knockout mice showed only minor deficiencies in energy homeostasis, feeding, and anxiety (11)(12)(13)(14).…”

Section: N Europeptide Y (Npy) Is Widely Distributed In the Cnsmentioning

confidence: 99%

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Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care

Bertocchi

Oberto

Longo

et al. 2011

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

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Neuropeptide Y (NPY) plays an important role in stress, anxiety, obesity, and energy homeostasis via activation of NPY-Y1 receptors (Y1Rs) in the brain. However, global knockout of the Npy1r gene has low or no impact on anxiety and body weight. To uncover the role of limbic Y1Rs, we generated conditional knockout mice in which the inactivation of the Npy1r gene was restricted to excitatory neurons of the forebrain, starting from juvenile stages (Npy1r rfb ). Npy1r rfb mice exhibited increased anxiety and reduced body weight, less adipose tissue, and lower serum leptin levels. Npy1r rfb mutants also had a hyperactive hypothalamic-pituitaryadrenocortical axis, as indicated by higher peripheral corticosterone and higher density of NPY immunoreactive fibers and corticotropin releasing hormone immunoreactive cell bodies in the paraventricular hypothalamic nucleus. Importantly, through fostering experiments, we determined that differences in phenotype between Npy1r rfb and Npy1r 2lox mice became apparent when both genotypes were raised by FVB/J but not by C57BL/6J dams, suggesting that limbic Y1Rs are key targets of maternal care-induced programming of anxiety and energy homeostasis. where it is involved in the regulation of anxiety, stress reactions, energy balance, circadian rhythms, and cognition (1-3). Clinical studies suggest that NPY plays an important role in the response to stress and in psychiatric disorders (4). In humans, NPY haploinsufficiency is correlated with characteristic brain responses to emotional and stress challenges and with trait anxiety (5). Intracerebroventricular injection of NPY reduces both anxiety-and stress-related behavior in several animal models, an effect that is primarily mediated by Y1 receptors (Y1Rs) expressed in amygdala, hippocampus, and locus coeruleus (6-9). The implications of a role of endogenous NPY in acting via Y1R to control emotionality, mood, and stress reactions have been probed with Y1R-selective antagonists and antisense oligonucleotides (1). NPY exerts its anxiolytic-like effect in the brain via interactions with the hypothalamic-pituitaryadrenocortical (HPA) axis and corticosteroids. Indeed, a functional antagonism between NPY and corticotropin releasing hormone (CRH) has been demonstrated in various CNS nuclei along the stress/anxiety circuits (10).In addition to its crucial role in emotional behavior, NPY potently stimulates feeding, reduces energy expenditure, and induces obesity via the activation of Y1R expressed in the hypothalamus (1). However, global Npy1r gene knockout mice showed only minor deficiencies in energy homeostasis, feeding, and anxiety (11)(12)(13)(14).To study the function of Y1R expressed in the limbic system and to exclude effects induced by the Npy1r gene inactivation in early development, we restricted the ablation of Y1R to excitatory neurons in the postnatal forebrain of mice by using the Cre-loxP system (Fig. 1A). In addition, because early postnatal environment can modulate NPY levels (15), gene-targeted pups were reared by two diffe...

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“…Despite being first characterised as a post-synaptic receptor, the Y1 receptor can also be found pre-synaptically and has a wide distribution both in the central nervous system as well as in the periphery [8] and [9]. Germline Y1 receptor knockout (Y1 −/− ) mice have a high bone mass phenotype with a generalised increase in bone formation on both cortical and cancellous surfaces [3].…”

Section: Introductionmentioning

confidence: 99%

Osteoblast specific Y1 receptor deletion enhances bone mass

Lee¹,

Nguyen²,

Enriquez³

et al. 2011

Bone

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Neuropeptide Y, Y1 receptors are found in neuronal as well as bone tissue and Y1 signalling has been implicated in the regulation of bone mass. However, the contribution of Y1 receptors located in these different tissues, particularly that of the bone-specific Y1 receptors, to the regulation of bone homeostasis is unclear. Here we demonstrate that osteoblastspecific Y1 receptor deletion resulted in a marked increase in femoral cancellous bone volume, trabecular thickness and trabecular number. This is the result of elevated osteoblast activity as shown by increased mineral apposition rate and bone formation rate, and is associated with an upregulation in the mRNA expression levels of alkaline phosphatase, osteocalcin and dentin matrix protein-1. Furthermore, osteoblastic Y1 receptor deletion also led to increased mineral apposition rate on both the endocortical and the periosteal surfaces resulting in increased femoral diameter. Together these data demonstrate a direct role for the Y1 receptor on osteoblasts in the regulation of osteoblast activity and bone formation in vivo and suggest that targeting Y1 receptor signalling directly in the bone may have potential therapeutic implications for stimulating bone accrual in diseases such as osteoporosis.

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Physiology and gene regulation of the brain NPY Y1 receptor

Cited by 128 publications

References 414 publications

Neuropeptide Y Suppresses Anorexigenic Output from the Ventromedial Nucleus of the Hypothalamus

Neuropeptide Y Suppresses Anorexigenic Output from the Ventromedial Nucleus of the Hypothalamus

Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care

Osteoblast specific Y1 receptor deletion enhances bone mass

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