PMID- 22982626
OWN - NLM
STAT- MEDLINE
DCOM- 20130416
LR  - 20211021
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 225
DP  - 2012 Dec 6
TI  - Effects of sex and chronic neonatal nicotine treatment on Na(2)(+)/K(+)/Cl(-) 
      co-transporter 1, K(+)/Cl(-) co-transporter 2, brain-derived neurotrophic factor, 
      NMDA receptor subunit 2A and NMDA receptor subunit 2B mRNA expression in the 
      postnatal rat hippocampus.
PG  - 105-17
LID - S0306-4522(12)00904-9 [pii]
LID - 10.1016/j.neuroscience.2012.09.002 [doi]
AB  - Chronic exposure to nicotine during the first postnatal week in rats, a 
      developmental period that corresponds to the third trimester of human gestation, 
      results in sexually dimorphic long-term functional defects in the adult 
      hippocampus. One potential cause could be the sex-specific differences in the 
      maturation of GABA(A) receptor-mediated responses from excitatory to inhibitory, 
      which depends on the expression of the Na(2+)/K(+)/Cl(-) co-transporter 1 (NKCC1) 
      and the K(+)/Cl(-) co-transporter 2 (KCC2). In the rat hippocampus, this switch 
      occurs during the first and second postnatal week in females and males, 
      respectively, and is regulated by nicotinic receptor activation. Excitatory 
      GABAergic signaling can increase brain-derived neurotrophic factor (BDNF) 
      expression, which might exacerbate sex differences by impacting synaptogenesis. 
      We hypothesized that chronic neonatal nicotine (CNN) exposure differentially 
      regulates the expression of these co-transporters and BDNF in males and females. 
      We use quantitative isotopic in situ hybridization to examine the expression of 
      mRNAs for NKCC1, KCC2, BDNF, and NMDA receptor subunit 2A (NR2A) and NMDA 
      receptor subunit 2B (NR2B) in the postnatal day (P) 5 and 8 rat hippocampi in 
      both sexes that were either control-treated or with 6mg/kg/day nicotine in milk 
      formula (CNN) via gastric intubation starting at P1. In line with prolonged 
      GABAergic excitation, we found that at P5 males had significantly higher mRNA 
      expression of NKCC1 and BDNF than females. CNN treatment resulted in a 
      significant increase in KCC2 and BDNF mRNA expression in male but not female 
      hippocampus (p<0.05). Males also had higher expression of NR2A and lower 
      expression of NR2B at P5 compared to females (p<0.05). At P8, there were neither 
      sex nor treatment effects on mRNA expression, indicating the end of a critical 
      period for sensitivity to nicotine. These results suggest that differential 
      maturation of GABA(A)R-mediated responses result in sex-specific sensitivity to 
      nicotine during early postnatal development, potentially explaining the 
      differential long-term effects of CNN on hippocampal function.
CI  - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Damborsky, J C
AU  - Damborsky JC
AD  - Department of Neuroscience and Experimental Therapeutics, Texas A&M University 
      System Health Science Center, Medical Research and Education Building, 8447 State 
      Highway 47, Bryan, TX 77807-3260, USA.
FAU - Winzer-Serhan, U H
AU  - Winzer-Serhan UH
LA  - eng
GR  - T32 MH065728/MH/NIMH NIH HHS/United States
GR  - 2-T32-MH065728/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120912
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Sodium-Potassium-Chloride Symporters)
RN  - 6M3C89ZY6R (Nicotine)
RN  - VH92ICR8HX (N-methyl D-aspartate receptor subtype 2A)
SB  - IM
EIN - Neuroscience. 2012 Dec 27;227:381
MH  - Age Factors
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Developmental/*drug effects
MH  - Hippocampus/*drug effects/growth & development/metabolism
MH  - Male
MH  - Nicotine/*pharmacology
MH  - Nicotinic Agonists/*pharmacology
MH  - Pregnancy
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism
MH  - *Sex Characteristics
MH  - Sodium-Potassium-Chloride Symporters/genetics/*metabolism
MH  - Time Factors
PMC - PMC3485076
MID - NIHMS413871
EDAT- 2012/09/18 06:00
MHDA- 2013/04/17 06:00
PMCR- 2013/12/06
CRDT- 2012/09/18 06:00
PHST- 2012/05/18 00:00 [received]
PHST- 2012/08/27 00:00 [revised]
PHST- 2012/09/01 00:00 [accepted]
PHST- 2012/09/18 06:00 [entrez]
PHST- 2012/09/18 06:00 [pubmed]
PHST- 2013/04/17 06:00 [medline]
PHST- 2013/12/06 00:00 [pmc-release]
AID - S0306-4522(12)00904-9 [pii]
AID - 10.1016/j.neuroscience.2012.09.002 [doi]
PST - ppublish
SO  - Neuroscience. 2012 Dec 6;225:105-17. doi: 10.1016/j.neuroscience.2012.09.002. 
      Epub 2012 Sep 12.