PMID- 17026532
OWN - NLM
STAT- MEDLINE
DCOM- 20061207
LR  - 20131121
IS  - 0953-8194 (Print)
IS  - 0953-8194 (Linking)
VI  - 18
IP  - 11
DP  - 2006 Nov
TI  - Chronic prenatal ethanol exposure increases glucocorticoid-induced glutamate 
      release in the hippocampus of the near-term foetal guinea pig.
PG  - 826-34
AB  - Exposure to high cortisol concentration can injure the developing brain, possibly 
      via an excitotoxic mechanism involving glutamate (Glu). The present study tested 
      the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal 
      hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the 
      foetal compartment and alters sensitivity to glucocorticoid-induced Glu release 
      in the foetal hippocampus. Pregnant guinea pigs received daily oral 
      administration of ethanol (4 g/kg maternal body weight/day) or 
      isocaloric-sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, 
      approximately GD 68) at which time they were euthanised, 1 h after their final 
      treatment. Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were 
      determined in foetal plasma. Basal and electrically stimulated Glu and 
      gamma-aminobutyric acid (GABA) efflux in the presence or absence of dexamethasone 
      (DEX), a selective glucocorticoid-receptor agonist, were determined ex vivo in 
      foetal hippocampal slices. Glucocorticoid receptor (GR), mineralocorticoid 
      receptor (MR) and N-methyl-D-aspartate (NMDA) receptor NR1 subunit mRNA 
      expression were determined in situ in the hippocampus and dentate gyrus. In the 
      near-term foetus, CPEE increased foetal plasma ACTH and cortisol concentrations. 
      Electrically stimulated glutamate, but not GABA, release was increased in CPEE 
      foetal hippocampal slices. Low DEX concentration (0.3 microM) decreased 
      stimulated glutamate, but not GABA, release in both CPEE and control foetal 
      hippocampal slices. High DEX concentration (3.0 microM) increased basal release 
      of Glu, but not GABA, in CPEE foetal hippocampal slices. GR, but not MR, mRNA 
      expression was elevated in the hippocampus and dentate gyrus, whereas NR1 mRNA 
      expression was increased in the CA1 and CA3 fields of the foetal hippocampus. 
      These data demonstrate that CPEE increases high glucocorticoid 
      concentration-induced Glu release in the foetal hippocampus, presumably as a 
      consequence of increased GR expression. These effects of CPEE, coupled with 
      increased glutamate release and increased NMDA receptor expression, may 
      predispose the near-term foetal hippocampus to GR and Glu-NMDA receptor-mediated 
      neurodevelopmental toxicity.
FAU - Iqbal, U
AU  - Iqbal U
AD  - Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, 
      Canada.
FAU - Brien, J F
AU  - Brien JF
FAU - Kapoor, A
AU  - Kapoor A
FAU - Matthews, S G
AU  - Matthews SG
FAU - Reynolds, J N
AU  - Reynolds JN
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neuroendocrinol
JT  - Journal of neuroendocrinology
JID - 8913461
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Glucocorticoids)
RN  - 0 (Neurotoxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3K9958V90M (Ethanol)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adrenocorticotropic Hormone/blood
MH  - Animals
MH  - Central Nervous System Depressants/toxicity
MH  - Electric Stimulation
MH  - Ethanol/*toxicity
MH  - Female
MH  - Fetus/*drug effects/metabolism
MH  - Glucocorticoids/*metabolism
MH  - Glutamic Acid/*drug effects/metabolism
MH  - Guinea Pigs
MH  - Hippocampus/*drug effects/metabolism
MH  - Hydrocortisone/blood
MH  - Hypothalamo-Hypophyseal System/drug effects/metabolism
MH  - Maternal-Fetal Exchange
MH  - Neurotoxins/*toxicity
MH  - Organ Culture Techniques
MH  - Pituitary-Adrenal System/drug effects/metabolism
MH  - Pregnancy
MH  - RNA, Messenger/analysis
MH  - Random Allocation
MH  - Receptors, Glucocorticoid/drug effects/genetics/metabolism
MH  - Receptors, Mineralocorticoid/drug effects/genetics/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/metabolism
MH  - Statistics, Nonparametric
MH  - Toxicity Tests, Chronic
EDAT- 2006/10/10 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/10/10 09:00
PHST- 2006/10/10 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/10/10 09:00 [entrez]
AID - JNE1479 [pii]
AID - 10.1111/j.1365-2826.2006.01479.x [doi]
PST - ppublish
SO  - J Neuroendocrinol. 2006 Nov;18(11):826-34. doi: 10.1111/j.1365-2826.2006.01479.x.