Growth hormone replacement in hypophysectomized rats affects spatial performance and hippocampal levels of NMDA receptor subunit and PSD-95 gene transcript levels.
Clinical studies have demonstrated that growth hormone (GH) promotes learning and memory processes in GH-deficient (GHD) patients. In animal studies, GH also influences the N-methyl-D-aspartate (NMDA) receptor system in the hippocampus, an essential component of long-term potentiation (LTP), which is highly involved in memory acquisition. This study was designed to examine the beneficial effects of recombinant human GH (rhGH) on cognitive function in male rats with multiple hormone deficiencies resulting from hypophysectomy (Hx). The performance of an rhGH-treated group and an untreated control group was appraised in the Morris water maze (MWM). The rhGH-treated group performed significantly better in the spatial memory task than the control animals on the second and third trial days. Further training eliminated this difference between the groups. Hippocampal mRNA expression of the NMDA subunits NR1, NR2A and NR2B, insulin-like growth factor type 1 receptor (IGF-1R), and postsynaptic density protein-95 (PSD-95) was then measured in the animals by Northern blot analysis. The results suggest that there may be a relationship between the NMDA receptor subunit mRNA expression levels and learning ability, and that learning is improved by rhGH in Hx rats. Furthermore, a link between MWM performance and PSD-95 was also suggested by this study.
Le Grevès
Madeleine
M
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, P.O. Box 591, 751 24, Uppsala, Sweden. madeleine.legreves@farmbio.uu.se
Zhou
Qin
Q
Berg
Marita
M
Le Grevès
Pierre
P
Fhölenhag
Karin
K
Meyerson
Bengt
B
Nyberg
Fred
F
D000818:Animals; D015152:Blotting, Northern; D000076122:Disks Large Homolog 4 Protein; D013006:Growth Hormone / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D020249:Hormone Replacement Therapy; D007016:Hypophysectomy; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis*; D008568:Memory / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D013006:Growth Hormone