Characterization of NPY Y2 receptor protein expression in the mouse brain. II. Coexistence with NPY, the Y1 receptor, and other neurotransmitter-related molecules
ABSTRACT Neuropeptide Y (NPY) is widely expressed in the brain and its biological effects are mediated through a variety of receptors. We examined, using immunohistochemistry, expression of the Y2 receptor (R) protein in the adult mouse brain and its association with NPY and the Y1R, as well as a range of additional neurotransmitters and signaling-related molecules, which previously have not been defined. Our main focus was on the hippocampal formation (HiFo), amygdaloid complex, and hypothalamus, considering the known functions of NPY and the wide expression of NPY, Y1R, and Y2R in these regions. Y2R-like immunoreactivity (-LI) was distributed in nerve fibers/terminal endings throughout the brain axis, without apparent colocalization with NPY or the Y1R. Occasional coexistence between NPY- and Y1R-LI was found in the HiFo. Following colchicine treatment, Y2R-LI accumulated in cell bodies that coexpressed γ-aminobutyric acid (GABA) in a population of cells in the amygdaloid complex and lateral septal nucleus, but not in the HiFo. Instead, Y2R-positive nerve terminals appeared to surround GABA-immunoreactive (ir) cells in the HiFo and other neuronal populations, e.g., NPY-ir cells in HiFo and tyrosine hydroxylase-ir cells in the hypothalamus. In the HiFo, Y2R-ir mossy fibers coexpressed GABA, glutamic acid decarboxylase 67 and calbindin, and Y2R-LI was found in the same fibers that contained the presynaptic metabotropic glutamate receptor 2, but not together with any of the three vesicular glutamate transporters. Our findings provide further support that Y2R is mostly presynaptic, and that Y2Rs thus have a modulatory role in mediating presynaptic neurotransmitter release.
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- "The function of Y2R in anxiety is allegedly opposite of the Y1R subtype; however conflicting reports demonstrating both anxiogenic and anxiolytic effects mediated by Y2R make the role of this subtype in anxiety less clear. Y2R are generally considered NPY autoreceptors and evidence for their pre-synaptic localization has been demonstrated in humans and rodents (Stanic et al., 2011; Caberlotto et al., 1998). Central administration of Y2R agonists have failed to alter anxiety-like behavior in a number of studies (Broqua et al., 1995; Heilig et al., 1989; Britton et al., 1997; Sorensen et al., 2004). "
ABSTRACT: Repeated, extreme, or traumatic stressors can elicit pathological effects leading to many negative physical and psychological outcomes. Stressors can precipitate the onset of psychiatric diseases, or exacerbate pre-existing disorders including various anxiety and mood disorders. As stressors can negatively impact human psychiatric health, it is essential to identify neurochemicals that may confer protection from the negative sequelae of repeated or extreme stress exposure. Elucidating the neurobiological underpinnings of stress resilience will enhance our ability to promote resilience to, or recovery from, stress-related psychiatric disease. Herein, we will review the evidence for neuropeptide Y as an endogenous mediator of resilience and its potential relevance for the treatment of stress-related psychiatric diseases.01/2015; 1:33-43. DOI:10.1016/j.ynstr.2014.09.007
- "This hypothesis would indeed be in agreement with findings obtained in the context of food intake: mice deficient of the Y2 receptor are resistant to the anorectic effect of exogenous PYY 3–36 (Batterham et al., 2002), and pharmacological blockade of the Y2 receptor using a selective Y2 receptor antagonist abolishes the anorectic actions of PYY 3–36 in rats (Abbott et al., 2005). At high concentrations, however, PYY 3–36 may also bind to other Y receptor subtypes that are expressed in the CNS, including the Y1 receptor (Stanic et al., 2011). It thus remains to be explored whether the effects of exogenous PYY 3–36 treatment on incentive salience, short-term memory , and sensorimotor gating (Stadlbauer et al., 2013b, 2014) may be mediated by signaling at multiple Y receptor subclasses, or whether these may represent selective Y2 receptor-mediated effects. "
Article: PYY3–36: Beyond food intake[Show abstract] [Hide abstract]
ABSTRACT: The gastrointestinal hormone peptide tyrosine tyrosine 3-36 (PYY3-36) has attained broad recognition with respect to its involvement in energy homeostasis and the control of food intake. It is mainly secreted by distal intestinal enteroendocrine L-cells in response to eating and exerts both neurally mediated paracrine and endocrine effects on various target organs. In addition to its gastrointestinal effects, PYY3-36 has long been known to inhibit food intake. Recent closer examination of the effects of PYY3-36 revealed that this gut-derived peptide also influences a wide spectrum of behavioral and cognitive functions that are pivotal for basic processes of perception and judgment, including central information processing, salience learning, working memory, and behavioral responding to novelty. Here, we review the effects of PYY3-36 that go beyond food intake and provide a conceptual framework suggesting that several apparently unrelated behavioral actions of PYY3-36 may actually reflect different manifestations of modulating the central dopamine system. Copyright © 2014. Published by Elsevier Inc.Frontiers in Neuroendocrinology 12/2014; DOI:10.1016/j.yfrne.2014.12.003 · 7.58 Impact Factor
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- "NPY and particularly the Y2 receptor play an important role in neuroprotection against excitotoxicity. NPY not only inhibits excessive glutamate release but also protects neurons from excitotoxic cell death, and stimulation of presynaptic Y2 receptors has been found to inhibit glutamate release (Silva et al., 2003; Stanić et al., 2011; Vezzani and Sperk, 2004). The single nucleotide polymorphisms (SNPs) in this study were selected based on their established functional effects. "
ABSTRACT: Sensory memory systems are modality-specific buffers that comprise information about external stimuli, which represent the earliest stage of information processing. While these systems are subject to cognitive neuroscience research for decades, little is known about the neurobiological basis of sensory memory. However, accumulating evidence suggests that the glutamatergic system and systems influencing glutamatergic neural transmission are important. In the current study we examine if functional promoter variations in neuropeptide Y (NPY) and its receptor gene NPY2R affect iconic memory processes using a partial report paradigm. We found that iconic memory decayed much faster in individuals carrying the rare promoter NPY2R G allele which is associated with increased expression of the Y2 receptor. Possibly this effect is due to altered presynaptic inhibition of glutamate release, known to be modulated by Y2 receptors. Altogether, our results provide evidence that the functionally relevant single nucleotide polymorphism (SNP) in the NPY2R promoter gene affect circumscribed processes of early sensory processing; i.e. only the stability of information in sensory memory buffers. This lead us to suggest that especially the stability of information in sensory memory buffers depends on glutamatergic neural transmission and factors modulating glutamatergic turnover.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 08/2014; 24(8). DOI:10.1016/j.euroneuro.2014.03.003 · 5.40 Impact Factor