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Open Access Highly Accessed Research article

Ghrelin accelerates synapse formation and activity development in cultured cortical networks

Irina I Stoyanova1* and Joost le Feber12

Author Affiliations

1 Biomedical Signals and Systems, Faculty of Electrical Engineering, Mathematics and Computer Sciences, Institute for Biomedical Engineering and Technical Medicine MIRA, BSS, ZH 226, University of Twente, P.O. Box 217, Enschede 7500 AE, The Netherlands

2 Clinical Neuro Physiology, Faculty of Applied Natural Sciences, Institute for Biomedical Engineering and Technical Medicine MIRA, University of Twente, Enschede, The Netherlands

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BMC Neuroscience 2014, 15:49  doi:10.1186/1471-2202-15-49

Published: 17 April 2014

Abstract

Background

While 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.

Results

We 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.

Conclusions

Acylated ghrelin leads to earlier network formation and activation in cultured cortical neuronal networks, the latter being a possibly consequence of accelerated synaptogenesis.

Keywords:
Dissociated cortical neurons; Ghrelin; GHSR-1a; Electrophysiological activity; Synaptogenesis