Ghrelin accelerates synapse formation and activity development in cultured cortical networks

详细信息    查看全文

• 作者：Irina I Stoyanova ; Joost le Feber
• 关键词：Dissociated cortical neurons ; Ghrelin ; GHSR ; 1a ; Electrophysiological activity ; Synaptogenesis
• 刊名：BMC Neuroscience
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：15
• 期：1
• 全文大小：718 KB
• 参考文献：1. Kojima, M, Hosada, H, Date, Y, Nakazato, M, Matsuo, H, Kangawa, K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nat 402: pp. 656-660 CrossRef
  2. Hosoda, H, Kojima, M, Matsuo, H, Kangawa, K (2000) Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 279: pp. 909-913 CrossRef
  3. Ariyasu, H, Takaya, K, Tagami, T, Ogawa, Y, Hosoda, K, Akamizu, T, Suda, M, Koh, T, Natsui, K, Toyooka, S, Shirakami, G, Usui, T, Shimatsu, A, Doi, K, Hosoda, H, Kojima, M, Kangawa, K, Nakao, K (2001) Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 86: pp. 4753-4758 CrossRef
  4. Delhanty, PJ, Neggers, SJ, Van der Lely, AJ (2012) Mechanisms in endocrinology: ghrelin: the differences between acyl- and des-acyl ghrelin. Eur J Endocrinol 167: pp. 601-608 CrossRef
  5. Van der Lely, AJ, Tsch?p, M, Heiman, ML, Ghigo, E (2004) Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 25: pp. 426-457 CrossRef
  6. Howard, AD, Feighner, SD, Cully, DF, Arena, JP, Liberator, PA, Rosenblum, CI, Hamelin, M, Hreniuk, DL, Palyha, OC, Anderson, J, Paress, PS, Diaz, C, Chou, M, Liu, KK, McKee, KK, Pong, SS, Chaung, LY, Elbrecht, A, Dashkevicz, M, Heavens, R, Rigby, M, Sirinathsinghji, DJ, Dean, DC, Melillo, DG, Patchett, AA, Nargund, R, Griffin, PR, DeMartino, JA, Gupta, SK, Schaeffer, JM (1996) A receptor in pituitary and hypothalamus that functions in growth hormone release. Sci 273: pp. 974-977 CrossRef
  7. Chan, CB, Cheng, CH (2004) Identification and functional characterization of two alternatively spliced growth hormone secretagogue receptor transcripts from the pituitary of black seabream Acanthopagrus schlegeli. Mol Cell Endocrinol 214: pp. 81-95 CrossRef
  8. Takahashi, K, Furukawa, C, Takano, A, Ishikawa, N, Kato, T, Hayama, S, Suzuki, C, Yasui, W, Inai, K, Sone, S, Ito, T, Nishimura, H, Tsuchiya, E, Nakamura, Y, Daigo, Y (2006) The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer. Cancer Res 66: pp. 9408-9419 CrossRef
  9. Kaiya, H, Kojima, M, Hosoda, H, Koda, A, Yamamoto, K, Kitajima, Y, Matsumoto, M, Minamitake, Y, Kikuyama, S, Kangawa, K (2001) Bullfrog ghrelin is modified by n-octanoic acid at its third threonine residue. J Biol Chem 276: pp. 40441-40448 CrossRef
  10. Kojima, M, Kangawa, K (2005) Ghrelin: structure and function. Physiol Rev 85: pp. 495-522 CrossRef
  11. Tsch?p, M, Smiley, DL, Heiman, ML (2000) Ghrelin induces adiposity in rodents. Nat 407: pp. 908-913 CrossRef
  12. Guan, XM, Yu, H, Palyha, OC, McKee, KK, Feighner, SD, Sirinathsinghji, DJ, Smith, RG, Van der Ploeg, LH, Howard, AD (1997) Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral issues. Brain Res Mol Brain Res 48: pp. 23-29 CrossRef
  13. Muccioli, G, Ghe, C, Ghigo, MC, Papotti, M, Arvat, E, Boghen, MF, Nilsson, MH, Deghenghi, R, Ong, H, Ghigo, E (1998) Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland. J Endocrinol 157: pp. 99-106 CrossRef
  14. Zigman, JM, Jones, JE, Lee, CE, Saper, CB, Elmquist, JK (2006) Expression of ghrelin receptor mRNA in the rat and the mouse
• 刊物主题：Neurosciences; Neurobiology; Animal Models;
• 出版者：BioMed Central
• ISSN：1471-2202

文摘

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?±-.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- 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.