Time-dependent changes in ghrelin-immunoreactivity in dissociated neuronal cultures of the newborn rat neocortex

Stoyanova, Irina; Wiertz, Remy; Rutten, Wim

doi:10.1016/j.regpep.2009.06.008

Cited by 7 publications

(8 citation statements)

References 25 publications

(25 reference statements)

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“…Recently, ghrelin expression was found in dissociated cortical neurons with a clear conditioning- and time-related pattern in the transmitter appearance: very early ghrelin expression at a high level, followed by maturational decrease in the next two weeks of culturing [27,28]. This qualitatively mimics the in vivo time course of development of networks, the survival of which requires synapse consolidation and activation during the first two weeks [61,62].…”

Section: Discussionmentioning

confidence: 89%

“…This suggests a unique central role of ghrelin [25], in addition to its role as a peripheral hormone secreted by gastric endocrine glands [1]. Later on, ghrelinergic neurons have been detected also in the cerebral cortex [26-28] indicating that ghrelin might be involved in higher activities in the central nervous system, like reward, mood, learning and memory [29-32]. The central role of ghrelin has been further supported by the findings that ghrelin induces neurogenesis, as first described in the rat dorsal motor nucleus of the vagus nerve [33] and the nucleus of the solitary tract [34] and, subsequently in cultured hippocampal progenitor cells [35], the hippocampus of adult mice [36], and the rat spinal cord [37,38].…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Ghrelin accelerates synapse formation and activity development in cultured cortical networks

Stoyanova

Feber

2014

BMC Neurosci

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“…Ghrelin was found to be present in the majority of cultured newborn rat neurons (Stoyanova et al, 2009). Circulating acyl ghrelin was found to enter the hippocampus and to bind to neurons of the hippocampal formation, where it promoted dendritic spine synapse formation and generation of long-term potentiation (Diano et al, 2006).…”

Section: Memorymentioning

confidence: 99%

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

et al. 2009

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“…Ghrelin is multifunctional 28-aminoacid hormone and a neuropeptide originally not only found in the rat stomach [25], but also identified in the hypothalamus, to a lesser extent in the hippocampus and brain cortex [26–28], as well as in the adipose tissue [29]. Ghrelin gene encodes a precursor which is cleaved to produce first unacylated ghrelin (des-acyl ghrelin (DAG)) further transformed into acyl ghrelin (AG, also referred to as ghrelin) by esterification of the serine-3 residue with n -octanoic acid [30].…”

Section: Introductionmentioning

confidence: 99%

Acyl Ghrelin Improves Synapse Recovery in an In Vitro Model of Postanoxic Encephalopathy

et al. 2015

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Comatose patients after cardiac arrest have a poor prognosis. Approximately half never awakes as a result of severe diffuse postanoxic encephalopathy. Several neuroprotective agents have been tested, however without significant effect. In the present study, we used cultured neuronal networks as a model system to study the general synaptic damage caused by temporary severe hypoxia and the possibility to restrict it by ghrelin treatment. Briefly, we applied hypoxia (pO2 lowered from 150 to 20 mmHg) during 6 h in 55 cultures. Three hours after restoration of normoxia, half of the cultures were treated with ghrelin for 24 h, while the other, non-supplemented, were used as a control. All cultures were processed immunocytochemically for detection of the synaptic marker synaptophysin. We observed that hypoxia led to drastic decline of the number of synapses, followed by some recovery after return to normoxia, but still below the prehypoxic level. Additionally, synaptic vulnerability was selective: large- and small-sized neurons were more susceptible to synaptic damage than the medium-sized ones. Ghrelin treatment significantly increased the synapse density, as compared with the non-treated controls or with the prehypoxic period. The effect was detected in all neuronal subtypes. In conclusion, exogenous ghrelin has a robust impact on the recovery of cortical synapses after hypoxia. It raises the possibility that ghrelin or its analogs may have a therapeutic potential for treatment of postanoxic encephalopathy.

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Time-dependent changes in ghrelin-immunoreactivity in dissociated neuronal cultures of the newborn rat neocortex

Cited by 7 publications

References 25 publications

Ghrelin accelerates synapse formation and activity development in cultured cortical networks

Ghrelin accelerates synapse formation and activity development in cultured cortical networks

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

Acyl Ghrelin Improves Synapse Recovery in an In Vitro Model of Postanoxic Encephalopathy

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