PMID- 14998743
OWN - NLM
STAT- MEDLINE
DCOM- 20040615
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 112
IP  - 3
DP  - 2004 Mar
TI  - Critical periods for chlorpyrifos-induced developmental neurotoxicity: 
      alterations in adenylyl cyclase signaling in adult rat brain regions after 
      gestational or neonatal exposure.
PG  - 295-301
AB  - Developmental exposure to chlorpyrifos (CPF) alters the function of a wide 
      variety of neural systems. In the present study we evaluated the effects in 
      adulthood of CPF exposure of rats during different developmental windows, using 
      the adenylyl cyclase (AC) signaling cascade, which mediates the cellular 
      responses to numerous neurotransmitters. Animals were exposed on gestational days 
      (GD) 9-12 or 17-20 or on postnatal days (PN) 1-4 or 11-14 and assessed at PN60. 
      In addition to basal AC activity, we evaluated the responses to direct AC 
      stimulants (forskolin, Mn2+) and to isoproterenol, which activates signaling 
      through ss-adrenoceptors coupled to stimulatory G-proteins. CPF exposure in any 
      of the four periods elicited significant changes in AC signaling in a wide 
      variety of brain regions in adulthood. In general, GD9-12 was the least sensitive 
      stage, requiring doses above the threshold for impaired maternal weight gain, 
      whereas effects were obtained at subtoxic doses for all other regimens. Most of 
      the effects were heterologous, involving signaling elements downstream from the 
      receptors, and thus shared by multiple stimulants; superimposed on this basic 
      pattern, there were also selective alterations in receptor-mediated responses, in 
      G-protein function, and in AC expression and subtypes. Exposures conducted at 
      GD17-20 and later all produced sex-selective alterations. These results suggest 
      that developmental exposure to CPF elicits long-lasting alterations in 
      cell-signaling cascades that are shared by multiple neurotransmitter and hormonal 
      inputs; the resultant abnormalities of synaptic communication are thus likely to 
      occur in widespread neural circuits and their corresponding behaviors.
FAU - Meyer, Armando
AU  - Meyer A
AD  - Centro de Estudos da Saude do Trabalhador e Ecologia Humana, Escola Nacional de 
      Saude Publica, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil.
FAU - Seidler, Frederic J
AU  - Seidler FJ
FAU - Aldridge, Justin E
AU  - Aldridge JE
FAU - Tate, Charlotte A
AU  - Tate CA
FAU - Cousins, Mandy M
AU  - Cousins MM
FAU - Slotkin, Theodore A
AU  - Slotkin TA
LA  - eng
GR  - ES 10356/ES/NIEHS NIH HHS/United States
GR  - ES 10387/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 (Adrenergic beta-Agonists)
RN  - 0 (Insecticides)
RN  - 0 (Receptors, Adrenergic, beta)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - JCS58I644W (Chlorpyrifos)
RN  - L628TT009W (Isoproterenol)
SB  - IM
MH  - Adenylyl Cyclases/*pharmacology
MH  - Adrenergic beta-Agonists/administration & dosage/pharmacology
MH  - Animals
MH  - Brain/*drug effects/*embryology/growth & development
MH  - Chlorpyrifos/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Insecticides/*toxicity
MH  - Isoproterenol/administration & dosage/pharmacology
MH  - Male
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Adrenergic, beta/drug effects/physiology
MH  - Signal Transduction
PMC - PMC1241857
EDAT- 2004/03/05 05:00
MHDA- 2004/06/16 05:00
PMCR- 2004/03/01
CRDT- 2004/03/05 05:00
PHST- 2004/03/05 05:00 [pubmed]
PHST- 2004/06/16 05:00 [medline]
PHST- 2004/03/05 05:00 [entrez]
PHST- 2004/03/01 00:00 [pmc-release]
AID - 10.1289/ehp.6755 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2004 Mar;112(3):295-301. doi: 10.1289/ehp.6755.