Behavioral characterization of neuropeptide Y knockout mice

Bannon, Anthony W.; Seda, Jennifer; Carmouché, Michelle; Francis, Jonathan M.; Norman, Mark H.; Karbon, Bill; McCaleb, Michael L.

doi:10.1016/s0006-8993(00)02285-x

Cited by 268 publications

(164 citation statements)

References 27 publications

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“…Results from diverse molecular and genetic paradigms are consistent with the implication that NPY, in concert with co-expressed orexigenic AgrP, GABA and adrenergic transmitters, constitutes an obligatory orexigenic signaling modality that is intimately involved in propagation of the timely appetitive drive under the direction of photoperiodic and hormonal cues (7,11,(27)(28)(29)47,(49)(50)(51)54,(56)(57)(58)(59). Additional recent disclosures that the hard wiring for the timely operation of this interplay is established during postnatal development have put the notion that NPY is a physiological appetite transducer on firm footing (11,(28)(29)(30)49,64).…”

Section: Is Npy a Naturally Occurring Appetite Transducer?supporting

confidence: 56%

To subjugate NPY is to improve the quality of life and live longer

Kalra

2007

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The interactive network of Neuropeptide Y (NPY) and cohorts is necessary for integrating the hypothalamic regulation of appetite and energy expenditure with the endocrine and neuroendocrine systems on a daily basis. Genetic and environmental factors that produce an insufficiency of leptin restraint on NPY and cognate receptors deregulate the homeostasis to engender various lifethreatening risk factors. Recent studies from our laboratory show that neurotherapy consisting of a single central administration of recombinant adeno-associated virus vector encoding the leptin gene can repress the hypothalamic NPY system for the lifetime of rodents. A major benefit of this stable tonic restraint is deceleration of pathophysiologic sequalae that shorten life span. These include suppression of weight gain, fat accumulation, circulating adipokines, amelioration of major symptoms of metabolic syndrome, improved reproduction and bone health. Thus, sustained repression of NPY signaling in the hypothalamus by leptin transgene expression can improve the quality of life and extend longevity.

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Section: Is Npy a Naturally Occurring Appetite Transducer?supporting

confidence: 56%

To subjugate NPY is to improve the quality of life and live longer

Kalra

2007

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“…Although we did not demonstrate causality, only association of NPY with behavioral effects, multiple studies have already determined anxiolytic effects of NPY (for a review, see Heilig, 2004). Increased NPY expression or NPY administration is associated with anxiolytic effects, whereas decreased NPY expression or blockade of its receptors is anxiogenic (Bannon et al, 2000;Heilig and Murison, 1987;Sajdyk et al, 1999;Sorensen et al, 2004;Tschenett et al, 2003). Accordingly, increased NPY expression in the hippocampus after prenatal betamethasone exposure is congruent with anti-anxiety effects.…”

Section: Technical Considerationsmentioning

confidence: 55%

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Velı́šek

2006

Neuropsychopharmacol

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Repeated antenatal administration of betamethasone is frequently used as a life-saving treatment in obstetrics. However, limited information is available about the outcome of this therapy in children. The initial prospective studies indicate that there are behavioral impairments in children exposed to repeated courses of prenatal betamethasone during the third trimester of pregnancy. In this study, pregnant rats received two betamethasone injections on day 15 of gestation. Using immunohistochemistry, the expression of a powerful anxiolytic molecule neuropeptide Y (NPY) was determined on postnatal day (PN) 20 in the hippocampus and basolateral amygdala (structures related to anxiety and fear) of the offspring. Prenatal betamethasone exposure induced significant increases in NPY expression in the hippocampus but not in the amygdala. Indeed, behavioral tests in the offspring, between PN20 and PN22 in the open field, on the horizontal bar, and in the elevated plus maze, indicated decreases in anxiety, without impairments in motor performance or total activity. Decreased body weight in betamethasone-exposed rats confirmed long-lasting effects of prenatal exposure. Thus, prenatal betamethasone treatment consistently increases hippocampal NPY, with decreases in anxiety-related behaviors and hippocampal role in anxiety in rats. Animal models may assist in differentiation between pathways of the desired main effect of the antenatal corticosteroid treatment and pathways of unwanted side effects. This differentiation can lead to specific therapeutic interventions directed against the side effects without eliminating the beneficial main effect of the corticosteroid treatment.

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“…47 NPY-deficient mice show reduced food intake in response to fasting and an anxiety-like phenotype with increased startle response. 48 Several receptors mediate the physiological effects of NPY, and data suggest that the energy balance effects of NPY are mediated by both the NPY Y1 and Y5 receptors. NPY Y4 knockout mice display increased locomotor activity, less anxiety-like behaviour and behavioural despair, whereas behavioural characterization of NPY Y2 knockout mice revealed reduced attention and increased impulsivity.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree

et al. 2010

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Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental syndrome characterized by hyperactivity, inattention and increased impulsivity. To detect micro-deletions and micro-duplications that may have a role in the pathogenesis of ADHD, we carried out a genome-wide screen for copy number variations (CNVs) in a cohort of 99 children and adolescents with severe ADHD. Using high-resolution array comparative genomic hybridization (aCGH), a total of 17 potentially syndrome-associated CNVs were identified. The aberrations comprise 4 deletions and 13 duplications with approximate sizes ranging from 110 kb to 3 Mb. Two CNVs occurred de novo and nine were inherited from a parent with ADHD, whereas five are transmitted by an unaffected parent. Candidates include genes expressing acetylcholine-metabolizing butyrylcholinesterase (BCHE), contained in a de novo chromosome 3q26.1 deletion, and a brain-specific pleckstrin homology domaincontaining protein (PLEKHB1), with an established function in primary sensory neurons, in two siblings carrying a 11q13.4 duplication inherited from their affected mother. Other genes potentially influencing ADHD-related psychopathology and involved in aberrations inherited from affected parents are the genes for the mitochondrial NADH dehydrogenase 1 a subcomplex assembly factor 2 (NDUFAF2), the brain-specific phosphodiesterase 4D isoform 6 (PDE4D6) and the neuronal glucose transporter 3 (SLC2A3). The gene encoding neuropeptide Y (NPY) was included in a B3 Mb duplication on chromosome 7p15.2-15.3, and investigation of additional family members showed a nominally significant association of this 7p15 duplication with increased NPY plasma concentrations (empirical family-based association test, P = 0.023). Lower activation of the left ventral striatum and left posterior insula during anticipation of large rewards or losses elicited by functional magnetic resonance imaging links gene dose-dependent increases in NPY to reward and emotion processing in duplication carriers. These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome.

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Behavioral characterization of neuropeptide Y knockout mice

Cited by 268 publications

References 27 publications

To subjugate NPY is to improve the quality of life and live longer

To subjugate NPY is to improve the quality of life and live longer

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree

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