Abstract：OBJECTIVE: To explore the effects of low-dose chlorpyrifos (CPF) exposure on dopaminergic (DA) neurons in the midbrain substantia nigra and neural behavioral development in neonatal rats. METHODS: Postnatal 11 day old Sprague-Dawley rats were randomly assigned into CPF, menstruum dimethysulfoxide (DMSO) and normal saline (NS) groups. The rats in the CPF group were injected with low-dose CPF (5 mg/kg?d) on postnatal days 11-14. The two control groups were injected with DMSO or NS respectively. The rats were sacrificed on postnatal days 15, 20, 30, and 60. Body weight gain, outward appearance of brain tissue, the coefficient of brain and the water content of brain tissue were measured. Tyrosine hydroxylase (TH) expression in DA neurons in the midbrain substantial nigra was examined by immunohistochemical straining. Immune electron microscopy was used to examine the subcellular structure of DA neurons. Open field test, grip strength test, slope test and Morris water maze test were used to examine the neurobehavioral changes. RESULTS: The outward appearance of brain tissue was normal in the three groups. There were no significant differences in the absolute value of body weight gain, the coefficient of brain and the water content of brain tissue among the three groups. CPF exposure decreased the level of TH immunoreactivity (P<0.05) in the substantia nigra of CPF group since postnatal day 30 compared with the DMSO and NS groups. The subcellular structures of some DA neurons in the CPF group were impaired. Decreased motor activity and learning and memory impairments were observed in the CPF group compared with those in the DMSO and NS groups (P<0.05) since postnatal day 30.ConclusionsCPF exposure during the neonatal period can cause long-term motor activity and learning and memory impairments in accompany with DA neurons damage in the midbrain substantia nigra.
ZHANG Jie,ZHAO Ling-Ling,HU Zhi-Ping et al. Effects of low-dose chlorpyrifos exposure on dopaminergic neurons in the midbrain substantia nigra and neural behavioral development in neonatal rats[J]. CJCP, 2011, 13(12): 989-994.
［3］Centers for Disease Control and Prevention. National Report on Human Exposure to Environmental Chemicals［DB/OL］. ［February 2001］. http://www.cdc.gov/exposurereport.
［5］Icenogle LM, Christopher NC, Blackwelder WP, Caldwell DP, Qiao D, Seidler FJ, et al. Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation［J］. Neurotoxicol Teratol, 2004, 26(1): 95-101.
［6］Roy TS, Seidler FJ, Slotkin TA. Morphologic effects of subtoxic neonatal chlorpyrifos exposure in developing rat brain: regionally selective alterations in neurons and glia［J］. Brain Res Dev Brain Res, 2004 ,148(2): 197-206.
［7］Aldridge JE, Levin ED, Seidler FJ, Slotkin TA. Developmental exposure of rats to chlorpyrifos leads to behavioral alterations in adulthood, involving serotonergic mechanisms and resembling animal models of depression［J］. Environ Health Perspect, 2005,113(5): 527-531.
［8］Roy TS, Sharma V, Seidler FJ, Slotkin TA. Quantitative morphological assessment reveals neuronal and glial deficits in hippocampus after a brief subtoxic exposure to chlorpyrifos in neonatal rats［J］. Brain Res Dev Brain Res, 2005,155(1): 71-80.
［9］Venerosi A, Cutuli D, Colonnello V, Cardona D, Ricceri L, Calamandrei G. Neonatal exposure to chlorpyrifos affects maternal responses and maternal aggression of female mice in adulthood［J］. Neurotoxicol Teratol, 2008, 30(6): 468-474.
［10］Saulsbury MD, Heyliger SO, Wang K, Round D. Characterization of chlorpyrifos-induced apoptosis in placental cells［J］. Toxicology, 2008, 244(2-3): 98-110.
［11］Sachana M, Flaskos J, Sidiropoulou E, Yavari CA, Hargreaves AJ. Inhibition of extension outgrowth in differentiating rat C6 glioma cells by chlorpyrifos and chlorpyrifos oxon: effects on microtubule proteins［J］. Toxicol In Vitro, 2008, 22(5): 1387-1391.
［12］Howard AS, Bucelli R, Jett DA, Bruun D, Yang D, Lein PJ. Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures［J］. Toxicol Appl Pharmacol, 2005, 207(2): 112-124.
［13］Dam K, Seidler FJ, Slotkin TA. Chlorpyrifos exposure during a critical neonatal period elicits gender-selective deficits in the development of coordination skills and locomotor activity［J］. Brain Res Dev Brain Res, 2000, 121(2): 179-187.
［15］Gotoh O, Asano T, Koide T, Takakura K. Ischemic brain edema following occlusion of the middle cerebral artery in the rat［J］. Stroke, 1985, 16(1): 101-109.
［16］Alstott J, Timberlake W. Effects of rat sex differences and lighting on locomotor exploration of a circular open field with free-standing central corners and without peripheral walls［J］. Behav Brain Res, 2009,196(2): 214-219.
［19］Davis DL, Ahmed AK. Exposures from indoor spraying of chlorpyrifos pose greater health risks to children than currently estimated［J］. Environ Health Perspect,1998,106(6):299-301.
［22］Abelson JF, Kwan KY, O′Roak BJ, Baek DY, Stillman AA, Morgan TM, et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome［J］. Science ,2005,310(5746):317-320.
