Growth hormone modulates hippocampal excitatory synaptic transmission and plasticity in old rats.
Alterations in the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPA-R) and N-methyl-D-aspartate receptor (NMDA-R) have been documented in aged animals and may contribute to changes in hippocampal-dependent memory. Growth hormone (GH) regulates AMPA-R and NMDA-R-dependent excitatory transmission and decreases with age. Chronic GH treatment mitigates age-related cognitive decline. An in vitro CA1 hippocampal slice preparation was used to compare hippocampal excitatory transmission and plasticity in old animals treated for 6-8 months with either saline or GH. Our findings indicate that GH treatment restores NMDA-R-dependent basal synaptic transmission in old rats to young adult levels and enhances both AMPA-R-dependent basal synaptic transmission and long-term potentiation. These alterations in synaptic function occurred in the absence of changes in presynaptic function, as measured by paired-pulse ratios, the total protein levels of AMPA-R and NMDA-R subunits or in plasma or hippocampal levels of insulin-like growth factor-I. These data suggest a direct role for GH in altering age-related changes in excitatory transmission and provide a possible cellular mechanism through which GH changes the course of cognitive decline.
Department of Neurobiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Doris P
DP
Molina
Olusegun J
OJ
Ariwodola
Constance
C
Linville
William E
WE
Sonntag
Jeff L
JL
Weiner
Judy K
JK
Brunso-Bechtold
Michelle M
MM
Adams
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001703:Biophysics; D004558:Electric Stimulation; D004797:Enzyme-Linked Immunosorbent Assay; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D011916:Rats, Inbred F344; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C036615:bicuculline methobromide; D007334:Insulin-Like Growth Factor I; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005998:Glycine; D001640:Bicuculline