Skip to main content

Ghrelin and Memory

  • Chapter
  • First Online:
Central Functions of the Ghrelin Receptor

Part of the book series: The Receptors ((REC,volume 25))

Abstract

The 28-amino acid peptide ghrelin was originally identified as an orexigenic hormone involved in the regulation of an organism’s energy homeostasis. Besides its role in metabolic processes, accumulating evidence suggests that ghrelin also plays an important role in the cognitive aspects of energy homeostasis, in particular learning and memory. Several studies in rodents confirm enhancing effects of ghrelin on fear learning, object recognition and spatial memory, in particular when given before the encoding phase of memory formation. Several mechanisms of action, intracellular signaling pathways and neurotransmitters involved in ghrelin’s effects on memory processes have been revealed, including serotonin, dopamine, neuropeptide Y, and nitric oxide, whose interplay affects hippocampal processes of neuroplasticity. Research on the role of ghrelin in the cognition of nonrodent species including humans is sparse and less conclusive, sometimes even suggesting memory-impairing effects of ghrelin. However, the increasing body of evidence demonstrating memory-supporting and neuroprotective effects in rodent models calls for further research that elucidates ghrelin’s effects on human cognition and its prospect in the therapy and prophylaxis of neurological diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Albarran-Zeckler RG, Brantley AF, Smith RG (2012) Growth hormone secretagogue receptor (GHSR-1A) knockout mice exhibit improved spatial memory and deficits in contextual memory. Behav Brain Res 232:13–19

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Atcha Z, Chen W-S, Ong AB et al (2009) Cognitive enhancing effects of ghrelin receptor agonists. Psychopharmacology 206:415–427

    Article  CAS  PubMed  Google Scholar 

  • Balasko M, Cabanac M (1998) Behavior of juvenile lizards (Iguana iguana) in a conflict between temperature regulation and palatable food. Brain Behav Evol 52:257–262

    Article  CAS  PubMed  Google Scholar 

  • Banks WA (2012) Role of the blood-brain barrier in the evolution of feeding and cognition. Ann N Y Acad Sci 1264:13–19

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bayliss JA, Andrews ZB (2013) Ghrelin is neuroprotective in Parkinson’s disease: molecular mechanisms of metabolic neuroprotection. Ther Adv Endocrinol Metab 4:25–36

    Article  PubMed Central  PubMed  Google Scholar 

  • Bennett GW, Ballard TM, Watson CD et al (1997) Eff neuropeptides cogn funct. Exp Gerontol 32:451–469

    Article  CAS  PubMed  Google Scholar 

  • Bonn M, Schmitt A, Lesch K-P et al (2013) Serotonergic innervation and serotonin receptor expression of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei. Brain Struct Funct 218:421–435

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bredt DS, Snyder SH (1990) Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci USA 87:682–685

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Brunetti L, Recinella L, Orlando G et al (2002) Effects of ghrelin and amylin on dopamine, norepinephrine and serotonin release in the hypothalamus. Eur J Pharmacol 454:189–192

    Article  CAS  PubMed  Google Scholar 

  • Carlini VP, Gaydou RC, Schiöth HB et al (2007) Selective serotonin reuptake inhibitor (fluoxetine) decreases the effects of ghrelin on memory retention and food intake. Regul Pept 140:65–73

    Article  CAS  PubMed  Google Scholar 

  • Carlini VP, Ghersi M, Schiöth HB et al (2010a) Ghrelin and memory: differential effects on acquisition and retrieval. Peptides 31:1190–1193

    Article  CAS  PubMed  Google Scholar 

  • Carlini VP, Martini AC, Schiöth HB et al (2008) Decreased memory for novel object recognition in chronically food-restricted mice is reversed by acute ghrelin administration. Neuroscience 153:929–934

    Article  CAS  PubMed  Google Scholar 

  • Carlini VP, Monzón ME, Varas MM et al (2002) Ghrelin increases anxiety-like behavior and memory retention in rats. Biochem Biophys Res Commun 299:739–743

    Article  CAS  PubMed  Google Scholar 

  • Carlini VP, Perez MF, Salde E et al (2010b) Ghrelin induced memory facilitation implicates nitric oxide synthase activation and decrease in the threshold to promote LTP in hippocampal dentate gyrus. Physiol Behav 101:117–123

    Article  CAS  PubMed  Google Scholar 

  • Carlini VP, Varas MM, Cragnolini AB et al (2004) Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin. Biochem Biophys Res Commun 313:635–641

    Article  CAS  PubMed  Google Scholar 

  • Carvajal P, Carlini VP, Schiöth HB et al (2009) Central ghrelin increases anxiety in the Open Field test and impairs retention memory in a passive avoidance task in neonatal chicks. Neurobiol Learn Mem 91:402–407

    Article  CAS  PubMed  Google Scholar 

  • Chung H, Li E, Kim Y et al (2013) Multiple signaling pathways mediate ghrelin-induced proliferation of hippocampal neural stem cells. J Endocrinol 218:49–59

    Google Scholar 

  • Crespi F (2011) Influence of Neuropeptide Y and antidepressants upon cerebral monoamines involved in depression: an in vivo electrochemical study. Brain Res 1407:27–37

    Article  CAS  PubMed  Google Scholar 

  • Crowder JM, Croucher MJ, Bradford HF et al (1987) Excitatory amino acid receptors and depolarization-induced Ca2+ influx into hippocampal slices. J Neurochem 48:1917–1924

    Article  CAS  PubMed  Google Scholar 

  • Cuellar JN, Isokawa M (2011) Ghrelin-induced activation of cAMP signal transduction and its negative regulation by endocannabinoids in the hippocampus. Neuropharmacology 60:842–851

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dhillo WS, Bloom SR (2001) Hypothalamic peptides as drug targets for obesity. Curr Opin Pharmacol 1:651–655

    Article  CAS  PubMed  Google Scholar 

  • Diano S, Farr SA, Benoit SC et al (2006) Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci 9:381–388

    Article  CAS  PubMed  Google Scholar 

  • Dimitrova DZ, Mihov DN, Wang R et al (2007) Contractile effect of ghrelin on isolated guinea-pig renal arteries. Vascul Pharmacol 47:31–40

    Article  CAS  PubMed  Google Scholar 

  • Dos Santos V V, Rodrigues A L S, Lima T C de et al (2013) Ghrelin as a neuroprotective and palliative agent in Alzheimer’s and parkinson’s disease. Curr Pharm Des 19(38):6773–6790

    Google Scholar 

  • Dresler M, Kluge M, Genzel L et al (2010) Nocturnal administration of ghrelin does not promote memory consolidation. Pharmacopsychiatry 43:277–278

    Article  CAS  PubMed  Google Scholar 

  • Eccles JC (1983) Calcium in long-term potentiation as a model for memory. Neuroscience 10:1071–1081

    Article  CAS  PubMed  Google Scholar 

  • Flood JF, Baker ML, Hernandez EN et al (1989) Modulation of memory processing by neuropeptide Y varies with brain injection site. Brain Res 503:73–82

    Article  CAS  PubMed  Google Scholar 

  • Gahete MD, Córdoba-Chacón J, Kineman RD et al (2011) Role of ghrelin system in neuroprotection and cognitive functions: implications in Alzheimer’s disease. Peptides 32:2225–2228

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gahete MD, Rubio A, Córdoba-Chacón J et al (2010) Expression of the ghrelin and neurotensin systems is altered in the temporal lobe of Alzheimer’s disease patients. J Alzheimers Dis 22:819–828

    CAS  PubMed  Google Scholar 

  • Gass P, Wolfer DP, Balschun D et al (1998) Deficits in memory tasks of mice with CREB mutations depend on gene dosage. Learn Mem 5:274–288

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ghasemi R, Haeri A, Dargahi L et al (2013) Insulin in the Brain: sources, localization and functions. Mol Neurobiol 47:145–171

    Article  CAS  PubMed  Google Scholar 

  • Ghersi MS, Casas SM, Escudero C et al (2011) Ghrelin inhibited serotonin release from hippocampal slices. Peptides 32:2367–2371

    Article  CAS  PubMed  Google Scholar 

  • Goshadrou F, Kermani M, Ronaghi A et al (2013) The effect of ghrelin on MK-801 induced memory impairment in rats. Peptides 44:60–65

    Article  CAS  PubMed  Google Scholar 

  • Goshadrou F, Ronaghi A (2012) Attenuating the effect of Ghrelin on memory storage via bilateral reversible inactivation of the basolateral amygdale. Behav Brain Res 232:391–394

    Article  CAS  PubMed  Google Scholar 

  • Han X, Zhu Y, Zhao Y et al (2011) Ghrelin reduces voltage-gated calcium currents in GH3 cells via cyclic GMP pathways. Endocrine 40:228–236

    Article  CAS  PubMed  Google Scholar 

  • Harris EW, Ganong AH, Cotman CW (1984) Long-term potentiation in the hippocampus involves activation of N-methyl-D-aspartate receptors. Brain Res 323:132–137

    Article  CAS  PubMed  Google Scholar 

  • Holst B, Cygankiewicz A, Jensen TH et al (2003) High constitutive signaling of the ghrelin receptor–identification of a potent inverse agonist. Mol Endocrinol 17:2201–2210

    Article  CAS  PubMed  Google Scholar 

  • Isokawa M (2012) Cellular signal mechanisms of reward-related plasticity in the hippocampus. Neural Plasticity 2012:1–18

    Article  Google Scholar 

  • Jacoby SM, Currie PJ (2011) SKF 83566 attenuates the effects of ghrelin on performance in the object location memory task. Neurosci Lett 504:316–320

    Article  CAS  PubMed  Google Scholar 

  • Janmaat KRL, Byrne RW, Zuberbühler K (2006) Primates take weather into account when searching for fruits. Curr Biol 16:1232–1237

    Article  CAS  PubMed  Google Scholar 

  • Jiang H (2006) Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol Endocrinol 20:1772–1785

    Article  CAS  PubMed  Google Scholar 

  • Johansson I, Destefanis S, Aberg ND et al (2008) Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells. Endocrinology 149:2191–2199

    Article  CAS  PubMed  Google Scholar 

  • Kamegai J, Tamura H, Shimizu T et al (2001) Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Diabetes 50:2438–2443

    Article  CAS  PubMed  Google Scholar 

  • Kenny R, Cai G, Bayliss J A et al (2013) Endogenous ghrelin’s role in hippocampal neuroprotection after global cerebral ischemia: does endogenous ghrelin protect against global stroke? Am J Physiol Regul Integr Comp Physiol 304(11):R980–990 (1 Jun 2013)

    Google Scholar 

  • Kida S (2012) A functional role for CREB as a positive regulator of memory formation and LTP. Exp Neurobiol 21:136

    Article  PubMed Central  PubMed  Google Scholar 

  • Kojima M, Hosoda H, Date Y et al (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660

    Article  CAS  PubMed  Google Scholar 

  • Laviano A, Molfino A, Rianda S et al (2012) The growth hormone secretagogue receptor (GHSR). Curr Pharm Des 18:4749–4754

    Article  CAS  PubMed  Google Scholar 

  • Leibowitz SF, Shor-Posner G (1986) Brain serotonin eat behav. Appetite 7:1–14

    Article  CAS  PubMed  Google Scholar 

  • Li E, Chung H, Kim Y et al (2013) Ghrelin directly stimulates adult hippocampal neurogenesis: implications for learning and memory. Endocr J 60(6):781–789 (ePub 15 Feb 2013)

    Google Scholar 

  • Moon M, Kim S, Hwang L et al (2009) Ghrelin regulates hippocampal neurogenesis in adult mice. Endocr J 56:525–531

    Article  CAS  PubMed  Google Scholar 

  • Morgado-Bernal I (2011) Learning and memory consolidation: linking molecular and behavioral data. Neuroscience 176:12–19

    Article  CAS  PubMed  Google Scholar 

  • Neves G, Cooke SF, Bliss TVP (2008) Synaptic plasticity, memory and the hippocampus: a neural network approach to causality. Nat Rev Neurosci 9:65–75

    Article  CAS  PubMed  Google Scholar 

  • Parys JB, de Smedt H (2012) Inositol 1,4,5-trisphosphate and its receptors. Adv Exp Med Biol 740:255–279

    Article  CAS  PubMed  Google Scholar 

  • Pravosudov VV (2008) Mountain chickadees discriminate between potential cache pilferers and non-pilferers. Proc Biol Sci 275:55–61

    Article  PubMed Central  PubMed  Google Scholar 

  • Redrobe JP, Dumont Y, St-Pierre JA et al (1999) Multiple receptors for neuropeptide Y in the hippocampus: putative roles in seizures and cognition. Brain Res 848:153–166

    Article  CAS  PubMed  Google Scholar 

  • Sarrar L, Ehrlich S, Merle JV et al (2011) Cognitive flexibility and Agouti-related protein in adolescent patients with anorexia nervosa. Psychoneuroendocrinology 36:1396–1406

    Article  CAS  PubMed  Google Scholar 

  • Sato M, Nakahara K, Goto S et al (2006) Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord. Biochem Biophys Res Commun 350:598–603

    Article  CAS  PubMed  Google Scholar 

  • Shintani M, Ogawa Y, Ebihara K et al (2001) Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 50:227–232

    Article  CAS  PubMed  Google Scholar 

  • Spitznagel MB, Benitez A, Updegraff J et al (2010) Serum ghrelin is inversely associated with cognitive function in a sample of non-demented elderly. Psychiatry Clin Neurosci 64:608–611

    Article  CAS  PubMed  Google Scholar 

  • Theodoropoulou A, Metallinos IC, Psyrogiannis A et al (2012) Ghrelin and leptin secretion in patients with moderate Alzheimer’s disease. J Nutr Health Aging 16:472–477

    Article  CAS  PubMed  Google Scholar 

  • Turner E (1969) Hippocampus and memory. Lancet 2:1123–1126

    Article  CAS  PubMed  Google Scholar 

  • Unger MM, Möller JC, Mankel K et al (2011) Postprandial ghrelin response is reduced in patients with Parkinson’s disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson’s disease? J Neurol 258:982–990

    Article  CAS  PubMed  Google Scholar 

  • Voronin LL (1983) Long-term potentiation in the hippocampus. Neuroscience 10:1051–1069

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Zhang M (2012) The role of Ca2+-stimulated adenylyl cyclases in bidirectional synaptic plasticity and brain function. Rev Neurosci 23:67–78

    Article  PubMed  Google Scholar 

  • Warren MW, Hynan LS, Weiner MF (2012) Leptin and cognition. Dement Geriatr Cogn Disord 33:410–415

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yada T, Kohno D, Maejima Y et al (2012) Neurohormones, rikkunshito and hypothalamic neurons interactively control appetite and anorexia. Curr Pharm Des 18:4854–4864

    Article  CAS  PubMed  Google Scholar 

  • Yamazaki M, Aizawa S, Tanaka T et al (2012) Ghrelin increases intracellular Ca2+ concentration in the various hormone-producing cell types of the rat pituitary gland. Neurosci Lett 526:29–32

    Article  CAS  PubMed  Google Scholar 

  • Yamazaki M, Kobayashi H, Tanaka T et al (2004) Ghrelin-induced growth hormone release from isolated rat anterior pituitary cells depends on intracellullar and extracellular Ca2+ sources. J Neuroendocrinol 16:825–831

    Article  CAS  PubMed  Google Scholar 

  • Zhang W (2004) Ghrelin stimulates neurogenesis in the dorsal motor nucleus of the vagus. J Physiol 11:2280–2288

    Google Scholar 

  • Zhang W, Hu Y, Lin TR et al (2005) Stimulation of neurogenesis in rat nucleus of the solitary tract by ghrelin. Peptides 26:2280–2288

    Article  CAS  PubMed  Google Scholar 

  • Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicolas Kunath .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kunath, N., Dresler, M. (2014). Ghrelin and Memory. In: Portelli, J., Smolders, I. (eds) Central Functions of the Ghrelin Receptor. The Receptors, vol 25. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0823-3_10

Download citation

Publish with us

Policies and ethics