title: Caloric restriction eliminates the aging-related decline in NMDA and AMPA receptor subunits in the rat hippocampus and induces homeostasis.
abstract: Caloric restriction (CR) extends life span and ameliorates the aging-related decline in hippocampal-dependent cognitive function. In the present study, we compared subunit levels of NMDA and AMPA types of the glutamate receptor and quantified total synapses and multiple spine bouton (MSB) synapses in hippocampal CA1 from young (10 months), middle-aged (18 months), and old (29 months) Fischer 344xBrown Norway rats that were ad libitum (AL) fed or caloric restricted (CR) from 4 months of age. Each of these parameters has been reported to be a potential contributor to hippocampal function. Western blot analysis revealed that NMDA and AMPA receptor subunits in AL animals decrease between young and middle age to levels that are present at old age. Interestingly, young CR animals have significantly lower levels of glutamate receptor subunits than young AL animals and those lower levels are maintained across life span. In contrast, stereological quantification indicated that total synapses and MSB synapses are stable across life span in both AL and CR rats. These results indicate significant aging-related losses of hippocampal glutamate receptor subunits in AL rats that are consistent with altered synaptic function. CR eliminates that aging-related decline by inducing stable NMDA and AMPA receptor subunit levels.
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157-1010, USA. lshi@wfubmc.edu
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Adams
authors.forename: M Constance
authors.initials: MC
authors.lastname: Linville
authors.forename: Isabel G
authors.initials: IG
authors.lastname: Newton
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Forbes
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Long
authors.forename: David R
authors.initials: DR
authors.lastname: Riddle
authors.forename: Judy K
authors.initials: JK
authors.lastname: Brunso-Bechtold
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D031204:Caloric Restriction; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D015536:Down-Regulation / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D006706:Homeostasis / Q000502:physiology*; D008136:Longevity / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D046529:Microscopy, Electron, Transmission; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate