PMID- 14594624
OWN - NLM
STAT- MEDLINE
DCOM- 20040302
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 111
IP  - 14
DP  - 2003 Nov
TI  - Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects 
      during different critical periods.
PG  - 1736-43
AB  - During brain development, serotonin (5HT) provides essential neurotrophic 
      signals. In the present study, we evaluated whether the developmental 
      neurotoxicity of chlorpyrifos (CPF) involves effects on 5HT signaling, as a 
      potential mechanism underlying noncholinergic neuroteratogenic events. We 
      evaluated four different treatment windows ranging from the neural tube stage 
      [gestational days (GD) 9-12] and the late gestational period (GD17-20) through 
      postnatal phases of terminal neuronal differentiation and synaptogenesis 
      [postnatal days (PN) 1-4, PN11-14]. Exposure to CPF on GD9-12 elicited initial 
      suppression, immediately followed by rebound elevation, of 5HT1A and 5HT2 
      receptors as well as the 5HT transporter, all at doses below the threshold for 
      cholinergic hyperstimulation and the resultant systemic toxicity. In contrast, 
      with GD17-20 exposure, the initial effect was augmentation of all three 
      components by low doses of CPF. Sensitivity of these effects declined 
      substantially when exposure was shifted to the postnatal period. We also 
      identified major alterations in 5HT-mediated responses, assessed for the adenylyl 
      cyclase signaling cascade. Although GD9-12 exposure had only minor effects, 
      treatment on GD17-20 elicited supersensitivity to both stimulatory and inhibitory 
      responses mediated by 5HT. Our results indicate that CPF affects 5HT receptors, 
      the presynaptic 5HT transporter, and 5HT-mediated signal transduction during a 
      discrete critical gestational window. These effects are likely to contribute to 
      the noncholinergic component of CPF's developmental neurotoxicity.
FAU - Aldridge, Justin E
AU  - Aldridge JE
AD  - Department of Pharmacology and Cancer Biology, Duke University Medical Center, 
      Durham, North Carolina, USA.
FAU - Seidler, Frederic J
AU  - Seidler FJ
FAU - Meyer, Armando
AU  - Meyer A
FAU - Thillai, Indira
AU  - Thillai I
FAU - Slotkin, Theodore A
AU  - Slotkin TA
LA  - eng
GR  - ES10356/ES/NIEHS NIH HHS/United States
GR  - ES10387/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Carrier Proteins)
RN  - 0 (Insecticides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, rat)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - JCS58I644W (Chlorpyrifos)
SB  - IM
MH  - Adenylyl Cyclases/pharmacology
MH  - Animals
MH  - Brain/drug effects/*embryology
MH  - Carrier Proteins/*drug effects/physiology
MH  - Chlorpyrifos/*toxicity
MH  - Female
MH  - Insecticides/*toxicity
MH  - Membrane Glycoproteins/*drug effects/physiology
MH  - *Membrane Transport Proteins
MH  - *Nerve Tissue Proteins
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/*drug effects/physiology
MH  - Serotonin/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - Signal Transduction
PMC - PMC1241716
EDAT- 2003/11/05 05:00
MHDA- 2004/03/03 05:00
PMCR- 2003/11/01
CRDT- 2003/11/05 05:00
PHST- 2003/11/05 05:00 [pubmed]
PHST- 2004/03/03 05:00 [medline]
PHST- 2003/11/05 05:00 [entrez]
PHST- 2003/11/01 00:00 [pmc-release]
AID - 10.1289/ehp.6489 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2003 Nov;111(14):1736-43. doi: 10.1289/ehp.6489.