Developmental neurotoxicity elicited by prenatal or postnatal chlorpyrifos exposure: effects on neurospecific proteins indicate changing vulnerabilities.
The developmental neurotoxicity of the organophosphate pesticide chlorpyrifos (CPF) is thought to involve both neurons and glia, thus producing a prolonged window of vulnerability. To characterize the cell types and brain regions involved in these effects, we administered CPF to developing rats and examined neuroprotein markers for oligodendrocytes (myelin basic protein, MBP), for neuronal cell bodies (neurofilament 68 kDa, NF68), and for developing axons (neurofilament 200 kDa, NF200). Prenatal CPF administration on gestational days (GDs) 17-20 elicited an immediate (GD21) enhancement of MBP and NF68; by postnatal day (PN) 30, however, there were deficits in all three biomarkers, with the effect restricted to females. Exposure in the early postnatal period, PN1-4, did not evoke significant short-term or long-term changes in the neuroproteins. However, with treatment on PN11-14, we found reductions in MBP in the immediate posttreatment period (PN15, PN20) throughout the brain, and deficiencies across all three proteins emerged by PN30. With this regimen, males were targeted preferentially. The sex-selective effects seen here for the GD17-20 and PN11-14 regimens match those reported earlier for subsequent behavioral performance. These results indicate a shift in the populations of neural cells targeted by CPF, dependent upon the period of exposure. Similarly, developmental differences in the sex selectivity of the biochemical mechanisms underlying neurotoxicant actions are likely to contribute to discrete behavioral outcomes.
Garcia
Stephanie J
SJ
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
Seidler
Frederic J
FJ
Slotkin
Theodore A
TA
D000818:Animals; D001369:Axons / Q000187:drug effects; D001522:Behavior, Animal; D015415:Biomarkers / Q000032:analysis; D004390:Chlorpyrifos / Q000009:adverse effects*; D005260:Female; D007306:Insecticides / Q000009:adverse effects*; D008297:Male; D004676:Myelin Basic Protein / Q000032:analysis*; D016900:Neurofilament Proteins / Q000032:analysis*; D009474:Neurons / Q000187:drug effects; D009836:Oligodendroglia / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
D015415:Biomarkers; D007306:Insecticides; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D004390:Chlorpyrifos