Ghrelin controls hippocampal spine synapse density and memory performance
The gut hormone and neuropeptide ghrelin affects energy balance and growth hormone release through hypothalamic action that involves synaptic plasticity in the melanocortin system. Ghrelin binding is also present in other brain areas, including the telencephalon, where its function remains elusive....
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| Published in | Nature neuroscience Vol. 9; no. 3; pp. 381 - 388 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.03.2006
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1097-6256 1546-1726 |
| DOI | 10.1038/nn1656 |
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| Abstract | The gut hormone and neuropeptide ghrelin affects energy balance and growth hormone release through hypothalamic action that involves synaptic plasticity in the melanocortin system. Ghrelin binding is also present in other brain areas, including the telencephalon, where its function remains elusive. Here we report that circulating ghrelin enters the hippocampus and binds to neurons of the hippocampal formation, where it promotes dendritic spine synapse formation and generation of long-term potentiation. These ghrelin-induced synaptic changes are paralleled by enhanced spatial learning and memory. Targeted disruption of the gene that encodes ghrelin resulted in decreased numbers of spine synapses in the CA1 region and impaired performance of mice in behavioral memory testing, both of which were rapidly reversed by ghrelin administration. Our observations reveal an endogenous function of ghrelin that links metabolic control with higher brain functions and suggest novel therapeutic strategies to enhance learning and memory processes. |
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| AbstractList | The gut hormone and neuropeptide ghrelin affects energy balance and growth hormone release through hypothalamic action that involves synaptic plasticity in the melanocortin system. Ghrelin binding is also present in other brain areas, including the telencephalon, where its function remains elusive. Here we report that circulating ghrelin enters the hippocampus and binds to neurons of the hippocampal formation, where it promotes dendritic spine synapse formation and generation of long-term potentiation. These ghrelin-induced synaptic changes are paralleled by enhanced spatial learning and memory. Targeted disruption of the gene that encodes ghrelin resulted in decreased numbers of spine synapses in the CA1 region and impaired performance of mice in behavioral memory testing, both of which were rapidly reversed by ghrelin administration. Our observations reveal an endogenous function of ghrelin that links metabolic control with higher brain functions and suggest novel therapeutic strategies to enhance learning and memory processes. The gut hormone and neuropeptide ghrelin affects energy balance and growth hormone release through hypothalamic action that involves synaptic plasticity in the melanocortin system. Ghrelin binding is also present in other brain areas, including the telencephalon, where its function remains elusive. Here we report that circulating ghrelin enters the hippocampus and binds to neurons of the hippocampal formation, where it promotes dendritic spine synapse formation and generation of long-term potentiation. These ghrelin-induced synaptic changes are paralleled by enhanced spatial learning and memory. Targeted disruption of the gene that encodes ghrelin resulted in decreased numbers of spine synapses in the CA1 region and impaired performance of mice in behavioral memory testing, both of which were rapidly reversed by ghrelin administration. Our observations reveal an endogenous function of ghrelin that links metabolic control with higher brain functions and suggest novel therapeutic strategies to enhance learning and memory processes.The gut hormone and neuropeptide ghrelin affects energy balance and growth hormone release through hypothalamic action that involves synaptic plasticity in the melanocortin system. Ghrelin binding is also present in other brain areas, including the telencephalon, where its function remains elusive. Here we report that circulating ghrelin enters the hippocampus and binds to neurons of the hippocampal formation, where it promotes dendritic spine synapse formation and generation of long-term potentiation. These ghrelin-induced synaptic changes are paralleled by enhanced spatial learning and memory. Targeted disruption of the gene that encodes ghrelin resulted in decreased numbers of spine synapses in the CA1 region and impaired performance of mice in behavioral memory testing, both of which were rapidly reversed by ghrelin administration. Our observations reveal an endogenous function of ghrelin that links metabolic control with higher brain functions and suggest novel therapeutic strategies to enhance learning and memory processes. |
| Audience | Academic |
| Author | Pinto, Shirly Horvath, Tamas L Xu, Lin Yamada, Kelvin A Jaeger, Laura B Morley, John E McNay, Ewan C Banks, William A Diano, Sabrina Horvath, Balazs Gaskin, F Spencer Farr, Susan A Tschöp, Matthias H Sherwin, Robert S da Silva, Ivaldo Benoit, Stephen C Sleeman, Mark W Nonaka, Naoko |
| Author_xml | – sequence: 1 givenname: Sabrina surname: Diano fullname: Diano, Sabrina organization: Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, Department of Neurobiology, Yale University School of Medicine – sequence: 2 givenname: Susan A surname: Farr fullname: Farr, Susan A organization: Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, Department of Internal Medicine, Division of Geriatric Medicine, St. Louis University School of Medicine – sequence: 3 givenname: Stephen C surname: Benoit fullname: Benoit, Stephen C organization: Department of Psychiatry, University of Cincinnati – sequence: 4 givenname: Ewan C surname: McNay fullname: McNay, Ewan C organization: Department of Internal Medicine, Yale University School of Medicine – sequence: 5 givenname: Ivaldo surname: da Silva fullname: da Silva, Ivaldo organization: Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine – sequence: 6 givenname: Balazs surname: Horvath fullname: Horvath, Balazs organization: Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine – sequence: 7 givenname: F Spencer surname: Gaskin fullname: Gaskin, F Spencer organization: Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, Department of Internal Medicine, Division of Geriatric Medicine, St. Louis University School of Medicine – sequence: 8 givenname: Naoko surname: Nonaka fullname: Nonaka, Naoko organization: Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, Department of Internal Medicine, Division of Geriatric Medicine, St. Louis University School of Medicine – sequence: 9 givenname: Laura B surname: Jaeger fullname: Jaeger, Laura B organization: Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, Department of Internal Medicine, Division of Geriatric Medicine, St. Louis University School of Medicine – sequence: 10 givenname: William A surname: Banks fullname: Banks, William A organization: Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, Department of Internal Medicine, Division of Geriatric Medicine, St. Louis University School of Medicine – sequence: 11 givenname: John E surname: Morley fullname: Morley, John E organization: Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, Department of Internal Medicine, Division of Geriatric Medicine, St. Louis University School of Medicine – sequence: 12 givenname: Shirly surname: Pinto fullname: Pinto, Shirly organization: Department of Molecular Genetics, Howard Hughes Medical Institute, Rockefeller University – sequence: 13 givenname: Robert S surname: Sherwin fullname: Sherwin, Robert S organization: Department of Internal Medicine, Yale University School of Medicine – sequence: 14 givenname: Lin surname: Xu fullname: Xu, Lin organization: Department of Neurology, Washington University School of Medicine – sequence: 15 givenname: Kelvin A surname: Yamada fullname: Yamada, Kelvin A organization: Department of Neurology, Washington University School of Medicine – sequence: 16 givenname: Mark W surname: Sleeman fullname: Sleeman, Mark W organization: Regeneron Pharmaceuticals Inc – sequence: 17 givenname: Matthias H surname: Tschöp fullname: Tschöp, Matthias H organization: Department of Psychiatry, University of Cincinnati – sequence: 18 givenname: Tamas L surname: Horvath fullname: Horvath, Tamas L email: tamas.horvath@yale.edu organization: Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, Department of Neurobiology, Yale University School of Medicine, Section of Comparative Medicine, Yale University School of Medicine |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16491079$$D View this record in MEDLINE/PubMed |
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| CODEN | NANEFN |
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| SubjectTerms | Animal Genetics and Genomics Animals Behavioral Sciences Binding sites Biological Techniques Biomedical and Life Sciences Biomedicine Cell Differentiation - drug effects Cell Differentiation - physiology Dendritic Spines - drug effects Dendritic Spines - metabolism Dendritic Spines - ultrastructure Ghrelin Growth hormones Hippocampus (Brain) Hippocampus - drug effects Hippocampus - metabolism Hippocampus - ultrastructure Internal medicine Learning - drug effects Learning - physiology Long-Term Potentiation - drug effects Long-Term Potentiation - physiology Male Medicine Memory Memory - drug effects Memory - physiology Memory Disorders - drug therapy Memory Disorders - genetics Memory Disorders - metabolism Metabolism Mice Mice, Inbred C57BL Mice, Knockout Morphology Neurobiology Neurosciences Nootropic Agents - metabolism Nootropic Agents - pharmacology Peptide Hormones - genetics Peptide Hormones - pharmacology Physiological aspects Rats Rats, Sprague-Dawley Space Perception - drug effects Space Perception - physiology Synapses - drug effects Synapses - metabolism Synapses - ultrastructure Synaptic Transmission - drug effects Synaptic Transmission - genetics |
| Title | Ghrelin controls hippocampal spine synapse density and memory performance |
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