PMID- 14754568
OWN - NLM
STAT- MEDLINE
DCOM- 20040506
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 112
IP  - 2
DP  - 2004 Feb
TI  - Developmental exposure to chlorpyrifos elicits sex-selective alterations of 
      serotonergic synaptic function in adulthood: critical periods and regional 
      selectivity for effects on the serotonin transporter, receptor subtypes, and cell 
      signaling.
PG  - 148-55
AB  - During brain development, serotonin (5HT) provides essential neurotrophic 
      signals, and in earlier work, we found that developmental exposure to 
      chlorpyrifos (CPF) elicits short-term changes in 5HT systems. In the present 
      study, we evaluated the effects in adulthood after CPF exposures from the neural 
      tube stage [gestational days (GD) 9-12] and the late gestational period (GD17-20) 
      through postnatal neuronal differentiation and synaptogenesis [postnatal days 
      (PN) 1-4 and 11-14], using treatments below the threshold for systemic toxicity. 
      With exposure on GD9-12, CPF elicited global elevations in 5HT1A and 5HT2 
      receptors and in the 5HT presynaptic transporter. The GD17-20 treatment elicited 
      larger effects that displayed selectivity for regions with 5HT nerve terminals 
      and that were preferential for males. Although similar receptor up-regulation was 
      seen after PN1-4 exposure, the effects were larger in regions with 5HT cell 
      bodies; in addition, the presynaptic transporter was down-regulated in the nerve 
      terminal zones of females. The PN11-14 exposure had much smaller effects on 
      receptors but still elicited transporter suppression with the same regional and 
      sex selectivity. Although CPF exposure on GD17-20, PN1-4, or PN11-14 altered the 
      ability of 5HT to modulate adenylyl cyclase, this change did not correspond with 
      the effects on 5HT receptors, suggesting an additional set of effects on proteins 
      that transduce the 5HT signal. Our results indicate that CPF elicits long-lasting 
      changes in 5HT receptors, the presynaptic 5HT transporter, and 5HT-mediated 
      signal transduction after exposure in discrete developmental windows that range 
      from the neural tube stage through synaptogenesis. These effects are likely to 
      contribute to neurobehavioral teratology of CPF.
FAU - Aldridge, Justin E
AU  - Aldridge JE
AD  - Department of Pharmacology and Cancer Biology, Duke University Medical Center, 
      Durham, North Carolina 27710, USA.
FAU - Seidler, Frederic J
AU  - Seidler FJ
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, Non-U.S. Gov't
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  - JCS58I644W (Chlorpyrifos)
SB  - IM
CIN - Environ Health Perspect. 2004 Feb;112(2):A112-3. PMID: 14959713
MH  - Animals
MH  - Carrier Proteins/metabolism/pharmacology
MH  - Cell Differentiation
MH  - Central Nervous System/drug effects/*embryology
MH  - Chlorpyrifos/*toxicity
MH  - Female
MH  - Insecticides/*toxicity
MH  - Membrane Glycoproteins/metabolism/pharmacology
MH  - *Membrane Transport Proteins
MH  - *Nerve Tissue Proteins
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/*drug effects/*physiology
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - Signal Transduction/*drug effects
MH  - Synapses
PMC - PMC1241823
EDAT- 2004/02/03 05:00
MHDA- 2004/05/07 05:00
PMCR- 2004/02/01
CRDT- 2004/02/03 05:00
PHST- 2004/02/03 05:00 [pubmed]
PHST- 2004/05/07 05:00 [medline]
PHST- 2004/02/03 05:00 [entrez]
PHST- 2004/02/01 00:00 [pmc-release]
AID - 10.1289/ehp.6713 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2004 Feb;112(2):148-55. doi: 10.1289/ehp.6713.