Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABA(A) receptor δ subunit in cerebellar granule neurons and delays motor development in rats.

Autor: Diaz MR; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA., Vollmer CC; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA., Zamudio-Bulcock PA; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA., Vollmer W; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA., Blomquist SL; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA., Morton RA; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA., Everett JC; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA., Zurek AA; Department of Physiology, University of Toronto, Toronto, Ontario, Canada., Yu J; Department of Physiology, University of Toronto, Toronto, Ontario, Canada., Orser BA; Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada; Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Valenzuela CF; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address: fvalenzuela@salud.unm.edu.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2014 Apr; Vol. 79, pp. 262-74. Date of Electronic Publication: 2013 Dec 04.
DOI: 10.1016/j.neuropharm.2013.11.020
Abstrakt: Exposure to ethanol (EtOH) during fetal development can lead to long-lasting alterations, including deficits in fine motor skills and motor learning. Studies suggest that these are, in part, a consequence of cerebellar damage. Cerebellar granule neurons (CGNs) are the gateway of information into the cerebellar cortex. Functionally, CGNs are heavily regulated by phasic and tonic GABAergic inhibition from Golgi cell interneurons; however, the effect of EtOH exposure on the development of GABAergic transmission in immature CGNs has not been investigated. To model EtOH exposure during the 3rd trimester-equivalent of human pregnancy, neonatal pups were exposed intermittently to high levels of vaporized EtOH from postnatal day (P) 2 to P12. This exposure gradually increased pup serum EtOH concentrations (SECs) to ∼60 mM (∼0.28 g/dl) during the 4 h of exposure. EtOH levels gradually decreased to baseline 8 h after the end of exposure. Surprisingly, basal tonic and phasic GABAergic currents in CGNs were not significantly affected by postnatal alcohol exposure (PAE). However, PAE increased δ subunit expression at P28 as detected by immunohistochemical and western blot analyses. Also, electrophysiological studies with an agonist that is highly selective for δ-containing GABA(A) receptors, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP), showed an increase in THIP-induced tonic current. Behavioral studies of PAE rats did not reveal any deficits in motor coordination, except for a delay in the acquisition of the mid-air righting reflex that was apparent at P15 to P18. These findings demonstrate that repeated intermittent exposure to high levels of EtOH during the equivalent of the last trimester of human pregnancy has significant but relatively subtle effects on motor coordination and GABAergic transmission in CGNs in rats.
(Copyright © 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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