Document Detail


Spatial memory formation and memory-enhancing effect of glucose involves activation of the tuberous sclerosis complex-Mammalian target of rapamycin pathway.
MedLine Citation:
PMID:  16885218     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The tuberous sclerosis complex-mammalian target of rapamycin (TSC-mTOR) cascade integrates growth factor and nutritional signals to regulate the synthesis of specific proteins. Because both growth factor signaling and glucose have been implicated in memory formation, we questioned whether mTOR activity is required for long-term spatial memory formation and whether this cascade is involved in the memory-augmenting effect of centrally applied glucose. To test our hypothesis, we directly administered rapamycin (an inhibitor of mTOR), glucose, 5-aminoimidazole-4-carboxamide-1beta-4-ribonucleoside (AICAR; an activator of AMP kinase), or glucose plus rapamycin into the dorsal hippocampus after we trained rats in the Morris water maze task. The results from these studies indicate that glucose enhances, whereas AICAR and rapamycin both impair, long-term spatial memory. Furthermore, the memory-impairing effect of targeted rapamycin administration could not be overcome by coadministration of glucose. Consistent with these behavioral results, biochemical analysis revealed that glucose and AICAR had opposing influences on the activation of the TSC-mTOR cascade, as indicated by the phosphorylation of ribosomal S6 kinase (S6K) and 4E binding protein 1 (4EBP1), targets of mTOR. Together, these findings suggest that memory formation requires the mTOR cascade and that the memory-enhancing effect of glucose involves its ability to activate this pathway.
Authors:
Pramod K Dash; Sara A Orsi; Anthony N Moore
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  26     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-03     Completed Date:  2006-09-05     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8048-56     Citation Subset:  IM    
Affiliation:
The Vivian L. Smith Center for Neurologic Research and Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA. p.dash@uth.tmc.edu
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MeSH Terms
Descriptor/Qualifier:
Aminoimidazole Carboxamide / administration & dosage,  analogs & derivatives
Animals
Dose-Response Relationship, Drug
Drug Combinations
Glucose / administration & dosage*
Hippocampus / drug effects,  physiology
Maze Learning / drug effects,  physiology*
Protein Kinases / metabolism*
Rats
Rats, Long-Evans
Ribonucleotides / administration & dosage
Signal Transduction / drug effects,  physiology*
Sirolimus / administration & dosage*
Space Perception / drug effects,  physiology*
Tumor Suppressor Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
MH072933/MH/NIMH NIH HHS; NS049160/NS/NINDS NIH HHS; NS35457/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Drug Combinations; 0/Ribonucleotides; 0/Tumor Suppressor Proteins; 169027-60-5/tuberous sclerosis complex 2 protein; 3031-94-5/AICA ribonucleotide; 360-97-4/Aminoimidazole Carboxamide; 50-99-7/Glucose; 53123-88-9/Sirolimus; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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