Selective expression of Narp, a secreted neuronal pentraxin, in orexin neurons

Reti, Irving M.; Reddy, Radhika; Worley, Paul F.; Baraban, Jay M.

doi:10.1046/j.1471-4159.2002.01141.x

Cited by 94 publications

(74 citation statements)

References 29 publications

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“…This identified 220 probe sets, representing products from 188 genes (Table 1; Supplemental Table S1), and included a significant overlap with the few known Hcrt cell markers Hcrt, Nptx2, Pdyn, and Igfpb3 (P < 10 3 10 À100 , x 2 test) (Reti et al 2002;Crocker et al 2005;Honda et al 2009). …”

Section: Identification Of Transcripts Enriched In the Hcrt Neuron Trmentioning

confidence: 99%

Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation

et al. 2013

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Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the molecular phenotype of these cells; previous attempts at comprehensive profiling had only limited sensitivity or were inaccurate. We generated a Hcrt translating ribosome affinity purification (bacTRAP) line for comprehensive translational profiling of all ribosome-bound transcripts in these neurons in vivo. From this profile, we identified >6000 transcripts detectably expressed above background and 188 transcripts that are highly enriched in these neurons, including all known markers of the cells. Blinded analysis of in situ hybridization databases suggests that 60% of these are expressed in a Hcrt marker-like pattern. Fifteen of these were confirmed with double labeling and microscopy, including the transcription factor Lhx9. Ablation of this gene results in a >30% loss specifically of Hcrt neurons, without a general disruption of hypothalamic development. Polysomnography and activity monitoring revealed a profound hypersomnolence in these mice. These data provide an in-depth and accurate profile of Hcrt neuron gene expression and suggest that Lhx9 may be important for specification or survival of a subset of these cells.[Keywords: translational profiling; hypocretin; orexin; bacTRAP; Lhx9; narcolepsy] Supplemental material is available for this article. Narcolepsy is a profound disorder of sleep regulation, characterized by excessive daytime sleepiness, sleep attacks, cataplexy, and sleep-onset REM (rapid eye movement) periods. Studies indicate that narcolepsy, especially when accompanied by cataplexy, is due to the absence of hypocretinergic neurons and signaling (Nishino et al. 2000;Thannickal et al. 2000;Bourgin et al. 2008). The hypocretins (Hcrts; also called orexins) are peptidergic neurotransmitters used by a discrete population of neurons in the lateral hypothalamus Sakurai et al. 1998). In model organisms, disruption of the gene encoding the Hcrt peptides or a Hcrt receptor (Chemelli et al. 1999;Lin et al. 1999) or, alternatively, the ablation of the neurons producing Hcrt (Gerashchenko et al. 2001;Hara et al. 2001;Zhang et al. 2007) recapitulates features of narcolepsy. In humans, there are two variations of the disorder: narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwoC). NC is strongly linked and associated with the HLA DQB1*0602 allele, a T-cell receptor locus, and P2RY11, a receptor that can regulate immune cell survival (Hallmayer et al. 2009;Kornum et al. 2011). This strongly suggests involvement of the immune system in the etiology of NC, while the involvement in NwoC is less clear. Cold Spring Harbor Laboratory Press on May 13, 2018 -Published by genesdev.cshlp.org Downloaded from

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Section: Identification Of Transcripts Enriched In the Hcrt Neuron Trmentioning

confidence: 99%

Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation

et al. 2013

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“…The heaviest staining of orexin-immunoreactive nerve endings in the brain was found in the paraventricular thalamic nucleus, arcuate nucleus of the hypothalamus, raphe nuclei, tuberomammillary nucleus (TMN), and locus ceruleus (LC). Orexin colocalizes with dynorphin , galanin (Håkansson et al, 1999), prolactin , neuronal activityregulated pentraxin (Reti et al, 2002), and glutamate (Abrahamson et al, 2001). Many orexin neurons express vesicular glutamate transporters, suggesting that many if not all orexin neurons are also glutamatergic (Rosin et al, 2003;Torrealba et al, 2003).…”

Section: Orexin-producing Neuronsmentioning

confidence: 99%

Orexin/Hypocretin: A Neuropeptide at the Interface of Sleep, Energy Homeostasis, and Reward System

2009

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“…Furthermore, even though Narp knockout (KO) mice perform normally on a variety of learning tasks, they are deficient in reward devaluation learning (Johnson et al, 2007). In addition, Narp expression is enriched in several limbic system areas, including the amygdala (Reti and Baraban, 2003), PFC (Lu et al, 2002), and orexin neurons of the hypothalamus (Reti et al, 2002a) that have been implicated in mediating drug-induced behaviors (Hyman et al, 2006;Carr and Kalivas, 2006). Accordingly, to investigate the role of Narp in drug abuse, we have, in this study, assessed the performance of Narp KO mice in two behaviors induced by morphine: locomotor sensitization and conditioned place preference.…”

Section: Introductionmentioning

confidence: 99%

Narp Deletion Blocks Extinction of Morphine Place Preference Conditioning

Crombag

Dickson

Dinenna

et al. 2008

Neuropsychopharmacol

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As drug abuse can be viewed as a maladaptive form of neuronal plasticity, attention has focused on defining the synaptic plasticity mechanisms that mediate the long-term effects of these drugs. As Narp is secreted at synaptic sites and binds to the extracellular surface of AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. Accordingly, to assess its potential role in the long-lasting behavioral effects of drugs of abuse, we have investigated the impact of Narp deletion on sustained behavioral responses elicited by repeated morphine administration. Narp knockout mice display normal locomotor sensitization and conditioned place preference, but are markedly resistant to extinction of place preference. Thus, these findings indicate that Narp plays a selective role in extinction, possibly by its effects on AMPA receptor trafficking.

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Selective expression of Narp, a secreted neuronal pentraxin, in orexin neurons

Cited by 94 publications

References 29 publications

Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation

Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation

Orexin/Hypocretin: A Neuropeptide at the Interface of Sleep, Energy Homeostasis, and Reward System

Narp Deletion Blocks Extinction of Morphine Place Preference Conditioning

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