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Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus slices through the modulation of N-methyl-D-aspartate receptors.
J Neurosci Res. 2004 Dec 01; 78(5):691-701.JN

Abstract

Among the different steroids found in the brain, pregnenolone sulfate (3beta-hydroxy-5-pregnen-20-one-3-sulfate; PREGS) is known to enhance hippocampal-associated memory. The present study employs rat hippocampal slices to investigate the ability of PREGS to modulate long-term potentiation (LTP), a phenomenon considered as a model of synaptic plasticity related to memory processes. LTP (3 x 100 Hz/1 sec within 2 min), implicated essentially glutamatergic transmission, for which the different synaptic events could be pharmacologically dissociated. We show that PREGS enhances LTP in CA1 pyramidal neurons at nanomolar concentrations and exhibits a bell-shaped concentration-response curve. The maximal effect of PREGS on both induction and maintenance phases of LTP is observed at 300 nM and requires 10 min of superfusion. Although PREGS does not change the N-methyl-D-aspartate (NMDA) component of the field potentials (fEPSPs) isolated in the presence of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in Mg2+-free artificial cerebrospinal fluid, PREGS does enhance the response induced by NMDA application (50 microM, 20 sec). PREGS does not modify the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component of the fEPSPs isolated in the presence of 100 microM DL-2-amino-7-phosphopentanoic acid (DL-AP5) or its potentiation induced by a single tetanic stimulation and the response induced by AMPA application (10 microM, 10 sec). Furthermore, PREGS does not affect the recurrent inhibition of the fEPSPs mediated by gamma-aminobutyric acid type A (GABA(A)) receptor. In conclusion, this study shows the ability of PREGS to enhance LTP in CA1 by accentuating the activity of NMDA receptors. This modulation of LTP might mediate the steroid-induced enhancement of memory.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale, Unité 488, Stéroïdes et Système Nerveux, Kremlin-Bicêtre, France.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15505794

Citation

Sliwinski, A, et al. "Pregnenolone Sulfate Enhances Long-term Potentiation in CA1 in Rat Hippocampus Slices Through the Modulation of N-methyl-D-aspartate Receptors." Journal of Neuroscience Research, vol. 78, no. 5, 2004, pp. 691-701.
Sliwinski A, Monnet FP, Schumacher M, et al. Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus slices through the modulation of N-methyl-D-aspartate receptors. J Neurosci Res. 2004;78(5):691-701.
Sliwinski, A., Monnet, F. P., Schumacher, M., & Morin-Surun, M. P. (2004). Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus slices through the modulation of N-methyl-D-aspartate receptors. Journal of Neuroscience Research, 78(5), 691-701.
Sliwinski A, et al. Pregnenolone Sulfate Enhances Long-term Potentiation in CA1 in Rat Hippocampus Slices Through the Modulation of N-methyl-D-aspartate Receptors. J Neurosci Res. 2004 Dec 1;78(5):691-701. PubMed PMID: 15505794.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus slices through the modulation of N-methyl-D-aspartate receptors. AU - Sliwinski,A, AU - Monnet,F P, AU - Schumacher,M, AU - Morin-Surun,M P, PY - 2004/10/27/pubmed PY - 2005/3/1/medline PY - 2004/10/27/entrez SP - 691 EP - 701 JF - Journal of neuroscience research JO - J Neurosci Res VL - 78 IS - 5 N2 - Among the different steroids found in the brain, pregnenolone sulfate (3beta-hydroxy-5-pregnen-20-one-3-sulfate; PREGS) is known to enhance hippocampal-associated memory. The present study employs rat hippocampal slices to investigate the ability of PREGS to modulate long-term potentiation (LTP), a phenomenon considered as a model of synaptic plasticity related to memory processes. LTP (3 x 100 Hz/1 sec within 2 min), implicated essentially glutamatergic transmission, for which the different synaptic events could be pharmacologically dissociated. We show that PREGS enhances LTP in CA1 pyramidal neurons at nanomolar concentrations and exhibits a bell-shaped concentration-response curve. The maximal effect of PREGS on both induction and maintenance phases of LTP is observed at 300 nM and requires 10 min of superfusion. Although PREGS does not change the N-methyl-D-aspartate (NMDA) component of the field potentials (fEPSPs) isolated in the presence of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in Mg2+-free artificial cerebrospinal fluid, PREGS does enhance the response induced by NMDA application (50 microM, 20 sec). PREGS does not modify the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component of the fEPSPs isolated in the presence of 100 microM DL-2-amino-7-phosphopentanoic acid (DL-AP5) or its potentiation induced by a single tetanic stimulation and the response induced by AMPA application (10 microM, 10 sec). Furthermore, PREGS does not affect the recurrent inhibition of the fEPSPs mediated by gamma-aminobutyric acid type A (GABA(A)) receptor. In conclusion, this study shows the ability of PREGS to enhance LTP in CA1 by accentuating the activity of NMDA receptors. This modulation of LTP might mediate the steroid-induced enhancement of memory. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/15505794/Pregnenolone_sulfate_enhances_long_term_potentiation_in_CA1_in_rat_hippocampus_slices_through_the_modulation_of_N_methyl_D_aspartate_receptors_ DB - PRIME DP - Unbound Medicine ER -