TY - JOUR
T1 - Understanding the mechanism of learning enhancement
T2 - NMDA and GABA receptor expression
AU - Toso, Laura
AU - Johnson, Andrea
AU - Bissell, Stephanie
AU - Roberson, Robin
AU - Abebe, Daniel
AU - Spong, Catherine Y.
N1 - Funding Information:
Supported by the Intramural Research Program of the National Institute of Child Health and Human Development and the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD.
PY - 2007/9
Y1 - 2007/9
N2 - Objective: The administration of neurotrophic peptides NAPVSIPQ (NAP) + SALLRSIPA (SAL) to aged mice resulted in significant learning enhancement. N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid (GABA) receptors are fundamental for learning because they are the major modulators of the long-term potentiation, the electrophysiologic mechanism for learning. Also, these receptors have been shown to be involved in NAP + SAL prevention of learning deficit in a mouse model for fetal alcohol syndrome, when administered prenatally during development. Our objective was to test whether NMDA and GABA receptors contribute to the learning enhancement that is induced by the peptides after adult administration. Study Design: Aged (14.5 months) male mice were treated for 10 consecutive days with placebo or D-NAP + D-SAL (20 μg, by gavage). At the end of the treatment, brains were harvested. Calibrator-normalized relative real-time polymerase chain reaction was performed with primers for GABA-Aβ3, GABA-Aα5, and the NMDA receptor subunits NR2A and NR2B, with GAPDH standardization. Statistical analysis included analysis of variance, with a probability value that was considered significant at <.05. Results: Five control brains and 6 brains from animals that were treated with NAP + SAL were collected. There was no difference in GABA-Aβ3, GABA-Aα5, NR2A, and NR2B subunits after adult administration of NAP + SAL, as compared with the controls (P > .05). Conclusion: Postnatal treatment with NAP + SAL induced learning enhancement in aged mice with a mechanism that does not involve alteration in NMDA and GABA receptor expression. Thus, the mechanism of learning enhancement might be different for a developing fetus than an adult or in the absence of a perturbing agent.
AB - Objective: The administration of neurotrophic peptides NAPVSIPQ (NAP) + SALLRSIPA (SAL) to aged mice resulted in significant learning enhancement. N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid (GABA) receptors are fundamental for learning because they are the major modulators of the long-term potentiation, the electrophysiologic mechanism for learning. Also, these receptors have been shown to be involved in NAP + SAL prevention of learning deficit in a mouse model for fetal alcohol syndrome, when administered prenatally during development. Our objective was to test whether NMDA and GABA receptors contribute to the learning enhancement that is induced by the peptides after adult administration. Study Design: Aged (14.5 months) male mice were treated for 10 consecutive days with placebo or D-NAP + D-SAL (20 μg, by gavage). At the end of the treatment, brains were harvested. Calibrator-normalized relative real-time polymerase chain reaction was performed with primers for GABA-Aβ3, GABA-Aα5, and the NMDA receptor subunits NR2A and NR2B, with GAPDH standardization. Statistical analysis included analysis of variance, with a probability value that was considered significant at <.05. Results: Five control brains and 6 brains from animals that were treated with NAP + SAL were collected. There was no difference in GABA-Aβ3, GABA-Aα5, NR2A, and NR2B subunits after adult administration of NAP + SAL, as compared with the controls (P > .05). Conclusion: Postnatal treatment with NAP + SAL induced learning enhancement in aged mice with a mechanism that does not involve alteration in NMDA and GABA receptor expression. Thus, the mechanism of learning enhancement might be different for a developing fetus than an adult or in the absence of a perturbing agent.
KW - N-methyl-d-aspartate (NMDA)
KW - activity-dependent neuroprotective protein (ADNP)
KW - activity-dependent neurotrophic factor (ADNF)
KW - gamma-aminobutyric acid (GABA)
KW - learning
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U2 - 10.1016/j.ajog.2007.05.049
DO - 10.1016/j.ajog.2007.05.049
M3 - Article
C2 - 17826414
AN - SCOPUS:34548449897
SN - 0002-9378
VL - 197
SP - 267.e1-267.e4
JO - American journal of obstetrics and gynecology
JF - American journal of obstetrics and gynecology
IS - 3
ER -