Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity.
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Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity. / Wijayawardhane, Nayana; Shonesy, Brian C; Vaithianathan, Thirumalini; Pandiella, Noemi; Vaglenova, Julia; Breese, Charles R; Dityatev, Alexander; Suppiramaniam, Vishnu.
in: NEUROBIOL DIS, Jahrgang 29, Nr. 1, 1, 2008, S. 81-91.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity.
AU - Wijayawardhane, Nayana
AU - Shonesy, Brian C
AU - Vaithianathan, Thirumalini
AU - Pandiella, Noemi
AU - Vaglenova, Julia
AU - Breese, Charles R
AU - Dityatev, Alexander
AU - Suppiramaniam, Vishnu
PY - 2008
Y1 - 2008
N2 - Ethanol-induced damage in the developing hippocampus may result in cognitive deficits such as those observed in fetal alcohol spectrum disorder (FASD). Cognitive deficits in FASD are partially mediated by alterations in glutamatergic synaptic transmission. Recently, we reported that synaptic transmission mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is impaired following fetal ethanol exposure. This finding led us to develop a rational approach for the treatment of alcohol-related cognitive deficits using aniracetam, an allosteric AMPAR modulator. In the present study, 28 to 34-day-old rats exposed to ethanol in utero were treated with aniracetam, and subsequently exhibited persistent improvement in mEPSC amplitude, frequency, and decay time. Furthermore, these animals expressed positive changes in synaptic single channel properties, suggesting that aniracetam ameliorates prenatal ethanol-induced deficits through modifications at the single channel level. Specifically, single channel open probability, conductance, mean open and closed times, and the number and burst duration were positively affected. Our findings emphasize the utility of compounds which slow the rate of deactivation and desensitization of AMPARs such as aniracetam.
AB - Ethanol-induced damage in the developing hippocampus may result in cognitive deficits such as those observed in fetal alcohol spectrum disorder (FASD). Cognitive deficits in FASD are partially mediated by alterations in glutamatergic synaptic transmission. Recently, we reported that synaptic transmission mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is impaired following fetal ethanol exposure. This finding led us to develop a rational approach for the treatment of alcohol-related cognitive deficits using aniracetam, an allosteric AMPAR modulator. In the present study, 28 to 34-day-old rats exposed to ethanol in utero were treated with aniracetam, and subsequently exhibited persistent improvement in mEPSC amplitude, frequency, and decay time. Furthermore, these animals expressed positive changes in synaptic single channel properties, suggesting that aniracetam ameliorates prenatal ethanol-induced deficits through modifications at the single channel level. Specifically, single channel open probability, conductance, mean open and closed times, and the number and burst duration were positively affected. Our findings emphasize the utility of compounds which slow the rate of deactivation and desensitization of AMPARs such as aniracetam.
M3 - SCORING: Zeitschriftenaufsatz
VL - 29
SP - 81
EP - 91
JO - NEUROBIOL DIS
JF - NEUROBIOL DIS
SN - 0969-9961
IS - 1
M1 - 1
ER -
