Effects of third trimester-equivalent ethanol exposure on Cl(-) co-transporter expression, network activity, and GABAergic transmission in the CA3 hippocampal region of neonatal rats. 2012

Julie C Everett, and Yamhilette Licón-Muñoz, and C Fernando Valenzuela
Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.

Fetal alcohol spectrum disorders are often associated with structural and functional hippocampal abnormalities, leading to long-lasting learning and memory deficits. The mechanisms underlying these abnormalities are not fully understood. Here, we investigated whether ethanol exposure during the 3rd trimester-equivalent period alters spontaneous network activity that is involved in neuronal circuit development in the CA3 hippocampal region. This activity is driven by GABA(A) receptors, which can have excitatory actions in developing neurons as a consequence of greater expression of the Cl(-) importer, NKCC1, with respect to expression of the Cl(-) exporter, KCC2, resulting in high [Cl(-)](i). Rat pups were exposed to ethanol vapor from postnatal day (P) 2-16 (4 h/day). Weight gain was significantly reduced in pups exposed to ethanol compared to control at P15 and 16. Brain slices were prepared immediately after the end of the 4-h exposure on P4-16 and experiments were also performed under ethanol-free conditions at the end of the exposure paradigm (P17-22). Ethanol exposure did not significantly affect expression of KCC2 or NKCC1, nor did it affect network activity in the CA3 hippocampal region. Ethanol exposure significantly decreased the frequency (at P9-11) and increased the amplitude (at P5-8 and P17-21) of GABA(A) receptor-mediated miniature postsynaptic currents. These data suggest that repeated in vivo exposure to ethanol during the 3rd trimester-equivalent period alters GABAergic transmission in the CA3 hippocampal region, an effect that could lead to abnormal circuit maturation and perhaps contribute to the pathophysiology of fetal alcohol spectrum disorders.

UI MeSH Term Description Entries
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D005260 Female Females
D000096922 K Cl- Cotransporters A subclass of symporters that specifically transport POTASSIUM and CHLORIDE ions across cellular membranes. Potassium chloride cotransporters play roles in regulating cell volume and intracellular chloride concentration. Electroneutral Potassium-Chloride Co-transporter 3,Electroneutral Potassium-Chloride Cotransporter 3,K Cl- Co-transporters,K(+), Cl(-)-Co-transporters,K(+), Cl(-)-Cotransporters,K-Cl Co-transporter,K-Cl Co-transporter 3,K-Cl Cotransporter,K-Cl Cotransporter 3,KCC2 Co-transporter,KCC2 Cotransporter,KCC3 Co-transporter,KCC3 Cotransporter,KCC4 Co-transporter,KCC4 Cotransporter,Potassium-Chloride Co-transporter 2,Potassium-Chloride Co-transporter 4,Potassium-Chloride Co-transporters,Potassium-Chloride Cotransporter 2,Potassium-Chloride Cotransporter 4,Potassium-Chloride Cotransporters,Potassium-Chloride Symporters,SLC12A5 Protein,SLC12A6 Protein,SLC12A7 Protein,Solute Carrier Family 12 Member 5,Solute Carrier Family 12 Member 6,Solute carrier family 12 member 7,Cl- Co-transporters, K,Co-transporter 2, Potassium-Chloride,Co-transporter 3, K-Cl,Co-transporter 4, Potassium-Chloride,Co-transporter, K-Cl,Co-transporter, KCC2,Co-transporter, KCC3,Co-transporter, KCC4,Co-transporters, K Cl-,Co-transporters, Potassium-Chloride,Cotransporter, K-Cl,Cotransporter, KCC2,Cotransporter, KCC3,Cotransporter, KCC4,Cotransporters, K Cl-,Cotransporters, Potassium-Chloride,Electroneutral Potassium Chloride Co transporter 3,Electroneutral Potassium Chloride Cotransporter 3,K Cl Co transporter,K Cl Co transporter 3,K Cl Co transporters,K Cl Cotransporter,K Cl Cotransporter 3,K Cl Cotransporters,KCC2 Co transporter,KCC3 Co transporter,KCC4 Co transporter,Potassium Chloride Co transporter 2,Potassium Chloride Co transporter 4,Potassium Chloride Co transporters,Potassium Chloride Cotransporter 2,Potassium Chloride Cotransporter 4,Potassium Chloride Cotransporters,Potassium Chloride Symporters,Protein, SLC12A5,Protein, SLC12A6,Protein, SLC12A7
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D056654 CA3 Region, Hippocampal A subsection of the hippocampus, described by Lorente de No, that is located between the HIPPOCAMPUS CA2 FIELD and the DENTATE GYRUS. CA3 Field of Hippocampus,CA3 Pyramidal Cell Area,CA3 Pyramidal Cell Layer,CA3 Stratum Lucidum,CA3 Stratum Pyramidale,CA3 Stratum Radiatum,Cornu Ammonis 3 Area,Hippocampal Sector CA3,Hippocampus CA3 Field,Regio Inferior of Hippocampus,Stratum Radiatum, CA3,CA3 Field, Hippocampus,CA3 Stratum Lucidums,CA3 Stratum Radiatums,CA3, Hippocampal Sector,Field, Hippocampus CA3,Hippocampal CA3 Region,Hippocampal CA3 Regions,Lucidum, CA3 Stratum,Lucidums, CA3 Stratum,Radiatum, CA3 Stratum,Radiatums, CA3 Stratum,Region, Hippocampal CA3,Sector CA3, Hippocampal,Stratum Lucidum, CA3,Stratum Lucidums, CA3,Stratum Pyramidale, CA3,Stratum Radiatums, CA3

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