NPY and its involvement in axon guidance, neurogenesis, and feeding

Hökfelt, Tomas; Stanić, Davor; Sanford, Staci D.; Gatlin, Jesse C.; Nilsson, Ida; Paratcha, Gustavo; Ledda, Fernanda; Fetissov, Sergueı̈ O.; Lindfors, Charlotte; Herzog, Herbert; Johansen, Jeanette E.; Ubink, Ruud; Pfenninger, Karl H.

doi:10.1016/j.nut.2008.06.010

Cited by 62 publications

(27 citation statements)

References 87 publications

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“…Moreover, a possible proliferative effect of NPY on neuroblasts in different areas of the neonatal and adult brain has been shown to be mediated mainly through Y1R (Howell et al 2003, 2005). In addition to the CNS, NPY has also been identified as a neurotrophic factor in the peripheral nervous system by showing its regenerative effect on olfactory epithelium (Hansel et al 2001, Hökfelt et al 2008). It has been shown that NPY acting through Y1R stimulates the proliferation of adult olfactory neuroblasts.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y innervation during fracture healing and remodeling

et al. 2010

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Background and purposeAutonomic neuropeptide Y (NPY) is involved in local bone remodeling via the central nervous system. However, the role of peripheral neuronal NPY in fracture healing is not known. We investigated the relationship between bone healing and side-specific occurrence of NPY in angular and straight fractures.MethodsTibial fractures in Sprague-Dawley rats were fixed with intramedullary pins in straight alignment and anterior angulation. The samples were analyzed by radiography, histology, and immunohistochemistry (IHC) between 3 and 56 days postfracture.ResultsIn the angular fractures, radiography and histology showed a 3.5-fold increase in callus thickness on the concave side compared to the convex side at day 21, whereas a 0.2-fold reduction in callus thickness was seen on the convex side between days 21 and 56. IHC showed regenerating NPY fibers in the callus and woven bone in both fractures at day 7. In angular fractures, a 5-fold increase in NPY fibers was observed on the concave side compared to the convex side at 7 days, whereas a 6-fold increase in NPY fibers was seen on the convex side between 21 and 56 days; only a 0.1-fold increase in NPY fibers was seen on the concave side during the same time period. In straight fractures, similar bony and neuronal changes were observed on both sides.InterpretationThe increase in NPY innervation on the convex side appears to correlate with the loss of callus thickness on the same side in angular fractures. Our results highlight the probable function of the peripheral NPY system in local bone remodeling.

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Section: Discussionmentioning

confidence: 99%

Neuropeptide Y innervation during fracture healing and remodeling

et al. 2010

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“…We hypothesize that the degeneration is a consequence of the lost input from the AGRP/NPY neurons, supported by Y1R degeneration also in target areas of the AGRP/ NPY neurons, such as the PVN. In fact, NPY has neuroprotective effects and is important in the development of the nervous system (see H€ okfelt et al, 2008;Xapelli et al, 2008). If so, MHC I proteins may be first expressed in the AGRP/NPY-and then the POMC neurons.…”

Section: Immediate Early Genesmentioning

confidence: 99%

Evidence of hypothalamic degeneration in the anorectic anx/anx mouse

Nilsson

Thams

Lindfors

et al. 2010

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Mice homozygous for the anorexia (anx) mutation are characterized by poor food intake and death by three to five weeks after birth. By P21 these mice display lower density of hypothalamic neuropeptides, including Agouti gene-related protein (AGRP). The AGRP/neuropeptide Y (NPY) system of the anx/anx mice develops normally until postnatal day (P) 12, then the normal increase in fiber density ceases, in some areas even distinctly decreases. This overlaps with activation of microglia, indicating an inflammatory and/or degenerative process. Here we studied, by in situ hybridization and immunohistochemistry (IHC), the expression of major histocompatibility complex (MHC) class I-related molecules and markers for cellular reactivity in hypothalamus of anx/anx mice. MHC class I transcript and -related proteins were found in arcuate nucleus (Arc), presumably both in neurons and glia, the latter also in areas innervated by AGRP (NPY) neurons. In the anx/anx hypothalamus, using TUNEL labeling, significantly higher number of apoptotic cells were found compared with +/+ mice, and active caspase 6 immunoreactivity was detected in degenerating NPY-fibers as well as signs of "microglia-associated cell death". In addition, Y1 receptor-labeled processes and soma of pro-opiomelanocortin (POMC) neurons, were markedly decreased at P21. These results support the hypothesis of degeneration of hypothalamic arcuate neuron populations in the anx/anx mice, whereby the AGRP system may be first affected, the changes in the POMC system being secondary in this process.

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“…Physiologically, NPY is involved in a variety of distinct processes, such as energy homeostasis, appetite, processing of pain, seizure suppression and importantly also in the modulation of emotional-affective behaviors (Hokfelt et al, 2008;Lee and Herzog, 2009;Lin et al, 2004;Loh et al, 2015;Sperk et al, 2007;Vezzani and Sperk, 2004). These effects are mediated by at least 5 different G-protein coupled receptors (Y1, Y2, Y4, Y5 and y6) (Michel et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

The role of Neuropeptide Y in fear conditioning and extinction

et al. 2016

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While anxiety disorders are the brain disorders with the highest prevalence and constitute a major burden for society, a considerable number of affected people are still treated insufficiently. Thus, in an attempt to identify potential new anxiolytic drug targets, neuropeptides have gained considerable attention in recent years. Compared to classical neurotransmitters they often have a regionally restricted distribution and may bind to several distinct receptor subtypes. Neuropeptide Y (NPY) is a highly conserved neuropeptide that is specifically concentrated in limbic brain areas and signals via at least 5 different G-protein-coupled receptors. It is involved in a variety of physiological processes including the modulation of emotional-affective behaviors. An anxiolytic and stress-reducing property of NPY is supported by many preclinical studies. Whether NPY may also interact with processing of learned fear and fear extinction is comparatively unknown. However, this has considerable relevance since pathological, inappropriate and generalized fear expression and impaired fear extinction are hallmarks of human post-traumatic stress disorder and a major reason for its treatment-resistance. Recent evidence from different laboratories emphasizes a fear-reducing role of NPY, predominantly mediated by exogenous NPY acting on Y1 receptors. Since a reduction of fear expression was also observed in Y1 receptor knockout mice, other Y receptors may be equally important. By acting on Y2 receptors, NPY promotes fear extinction and generates a long-term suppression of fear, two important preconditions that could support cognitive behavioral therapies in human patients. A similar effect has been demonstrated for the closely related pancreatic polypeptide (PP) when acting on Y4 receptors. Preliminary evidence suggests that NPY modulates fear in particular by activation of Y1 and Y2 receptors in the basolateral and central amygdala, respectively. In the basolateral amygdala, NPY signaling activates inhibitory G protein-coupled inwardly-rectifying potassium channels or suppresses hyperpolarization-induced I(h) currents in a Y1 receptor-dependent fashion, favoring a general suppression of neuronal activity. A more complex situation has been described for the central extended amygdala, where NPY reduces the frequency of inhibitory and excitatory postsynaptic currents. In particular the inhibition of long-range central amygdala output neurons may result in a Y2 receptor-dependent suppression of fear. The role of NPY in processes of learned fear and fear extinction is, however, only beginning to emerge, and multiple questions regarding the relevance of endogenous NPY and different receptor subtypes remain elusive. Y2 receptors may be of particular interest for future studies, since they are the most prominent Y receptor subtype in the human brain and thus among the most promising therapeutic drug targets when translating preclinical evidence to potential new therapies for human anxiety disorders.

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NPY and its involvement in axon guidance, neurogenesis, and feeding

Cited by 62 publications

References 87 publications

Neuropeptide Y innervation during fracture healing and remodeling

Neuropeptide Y innervation during fracture healing and remodeling

Evidence of hypothalamic degeneration in the anorectic anx/anx mouse

The role of Neuropeptide Y in fear conditioning and extinction

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