Expression of the ghrelin receptor gene in neurons of the medulla oblongata of the rat

Bron, Romke; Yin, Lei; Russo, Domenico; Furness, John B.

doi:10.1002/cne.23309

Cited by 21 publications

(22 citation statements)

References 75 publications

(131 reference statements)

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“…Although the highest concentration of it is found in the pituitary gland and hypothalamus, consistent with the known role of ghrelin in GH release and the regulation of body weight and metabolism [10,11], there is also abundant GHSR-1a expression in other, extra-hypothalamic areas including the cortex and brain stem [12-17] suggesting that ghrelin plays a much broader role [10,18,19]. A recent comparative study on hippocampal and cortical dissociated neurons showed that GHSR-1 mRNA expression is higher in the hippocampus than in the cortex, and depends on the maturation stage of the cultures [20].…”

Section: Introductionmentioning

confidence: 75%

Ghrelin accelerates synapse formation and activity development in cultured cortical networks

Stoyanova

Feber

2014

BMC Neurosci

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BackgroundWhile ghrelin was initially related to appetite stimulation and growth hormone secretion, it also has a neuroprotective effect in neurodegenerative diseases and regulates cognitive function. The cellular basis of those processes is related to synaptic efficacy and plasticity. Previous studies have shown that ghrelin not only stimulates synapse formation in cultured cortical neurons and hippocampal slices, but also alters some of the electrophysiological properties of neurons in the hypothalamus, amygdala and other subcortical areas. However, direct evidence for ghrelin’s ability to modulate the activity in cortical neurons is not available yet. In this study, we investigated the effect of acylated ghrelin on the development of the activity level and activity patterns in cortical neurons, in relation to its effect on synaptogenesis. Additionally, we quantitatively evaluated the expression of the receptor for acylated ghrelin – growth hormone secretagogue receptor-1a (GHSR-1a) during development.ResultsWe performed electrophysiology and immunohistochemistry on dissociated cortical cultures from neonates, treated chronically with acylated ghrelin. On average 76 ± 4.6% of the cortical neurons expressed GHSR-1a. Synapse density was found to be much higher in ghrelin treated cultures than in controls across all age groups (1, 2 or 3 weeks). In all cultures (control and ghrelin treated), network activity gradually increased until it reached a maximum after approximately 3 weeks, followed by a slight decrease towards a plateau. During early developmental stages (1–2 weeks), the activity was much higher in ghrelin treated cultures and consequently, they reached the plateau value almost a week earlier than controls.ConclusionsAcylated ghrelin leads to earlier network formation and activation in cultured cortical neuronal networks, the latter being a possibly consequence of accelerated synaptogenesis.

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Section: Introductionmentioning

confidence: 75%

Ghrelin accelerates synapse formation and activity development in cultured cortical networks

Stoyanova

Feber

2014

BMC Neurosci

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“…However, in the NTS known to receive afferent terminals of the gastric vagal innervation, we found only a small‐number of Fos‐ir cells in 6‐OHDA rats treated with HM01 compared to almost none by vehicle. In contrast, there was a 12.7‐fold increase in the number of Fos positive cells in the AP where GHS‐R1a are strongly expressed . This points to HM01 possible action through brainstem circuits regulating gastric function via the AP.…”

Section: Discussionmentioning

confidence: 91%

New ghrelin agonist, HM01 alleviates constipation and L‐dopa‐delayed gastric emptying in 6‐hydroxydopamine rat model of Parkinson's disease

Karasawa

Pietra

Giuliano

et al. 2014

Neurogastroenterology Motil

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Background Constipation and L-dopa-induced gastric dysmotility are common gastrointestinal (GI) symptoms in Parkinson’s disease (PD). We investigate the novel ghrelin agonist, HM01 influence on GI motor dysfunctions in 6-hydroxydopamine (6-OHDA) rats. Methods HM01 pharmacological profiles were determined in vitro and in vivo in rats. We assessed changes in fecal output and water content, and gastric emptying (GE) in 6-OHDA rats treated or not with orogastric (og) HM01 and L-dopa/carbidopa (LD/CD, 20/2 mg kg−1). Fos immunoreactivity (ir) cells in specific brain and lumbosacral spinal cord were quantified. Key results HM01 displayed a high binding affinity to ghrelin receptor (Ki: 1.42 ± 0.36 nM), 4.3±1.0 h half-life and high brain/plasma ratio. 6-OHDA rats had reduced daily fecal output (22%) and water intake (23%) compared to controls. HM01 (3 and 10 mg kg−1) similarly reversed the decreased 4-h fecal weight and water content in 6-OHDA rats. Basal GE was not modified in 6-OHDA rats, however, LD/CD (once or daily for 8 days) delayed GE in 6-OHDA and control rats that was prevented by HM01 (3 mg kg−1 acute or daily before LD/CD). HM01 increased Fos-ir cell number in the area postrema, arcuate nucleus, nucleus tractus solitarius and lumbosacral intermediolateral column of 6-OHDA rats where 6-OHDA had a lowering effect compared to controls. Conclusions & Inferences 6-OHDA rats display constipation- and adipsia-like features of PD and L-dopa-inhibited GE. The new orally active ghrelin agonist, HM01 crosses the blood brain barrier and alleviates these alterations suggesting a potential benefit for PD with GI disorders.

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“…The protocols for probe design and in situ hybridization have been described previously (Bron et al, ). In brief, the Fam38B (Piezo2), TRPM8, c‐Ret, and TrkB genes were identified in the guinea pig genome sequence (Broad Institute; Boston, MA; see http://asia.ensembl.org/Cavia_porcellus/Info/Index).…”

Section: Methodsmentioning

confidence: 99%

Piezo2 expression in corneal afferent neurons

Bron

Wood

Brock

et al. 2014

J of Comparative Neurology

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Recently, a novel class of mechanically sensitive channels has been identified and have been called Piezo channels. In this study, we explored Piezo channel expression in sensory neurons supplying the guinea pig corneal epithelium, which have well-defined modalities in this species. We hypothesized that a proportion of corneal afferent neurons express Piezo2, and that these neurons are neurochemically distinct from corneal polymodal nociceptors or cold-sensing neurons. We used a combination of retrograde tracing to identify corneal afferent neurons and double label in situ hybridization and/or immunohistochemistry to determine their molecular and/or neurochemical profile. We found that Piezo2 expression occurs in ∼26% of trigeminal ganglion neurons and 30% of corneal afferent neurons. Piezo2 corneal afferent neurons are almost exclusively non-calcitonin gene-related peptide (CGRP)-immunoreactive (-IR), medium- to large-sized neurons that are NF200-IR, suggesting they are not corneal polymodal nociceptors. There was no coexpression of Piezo2 and transient receptor potential cation channel subfamily M member 8 (TRPM8) transcripts in any corneal afferent neurons, further suggesting that Piezo2 is not expressed in corneal cold-sensing neurons. We also noted that TRPM8-IR or CGRP-IR corneal afferent neurons are almost entirely small and lack NF200-IR. Piezo2 expression occurs in a neurochemically distinct subpopulation of corneal afferent neurons that are not polymodal nociceptors or cold-sensing neurons, and is likely confined to a subpopulation of pure mechano-nociceptors in the cornea. This provides the first evidence in an in vivo system that Piezo2 is a strong candidate for a channel that transduces noxious mechanical stimuli.

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Expression of the ghrelin receptor gene in neurons of the medulla oblongata of the rat

Cited by 21 publications

References 75 publications

Ghrelin accelerates synapse formation and activity development in cultured cortical networks

Ghrelin accelerates synapse formation and activity development in cultured cortical networks

New ghrelin agonist, HM01 alleviates constipation and L‐dopa‐delayed gastric emptying in 6‐hydroxydopamine rat model of Parkinson's disease

Piezo2 expression in corneal afferent neurons

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