Neonatal exposure to paraquat or MPTP induces permanent changes in striatum dopamine and behavior in adult mice. 1993

A Fredriksson, and M Fredriksson, and P Eriksson
Department of Toxicology, Uppsala University, Sweden.

We have recently reported that environmental toxicants, such as DDT, PCBs, pyrethroids, and nicotine can induce permanent functional and neurochemical changes in adult mice when given to neonatal mice during the peak of rapid brain growth. In the present investigation the neurotoxic effects following neonatal exposure to paraquat (N,N'-dimethyl-4,4'-bipyridylium), a broad-spectrum herbicide with structural similarity to the 1-methyl-4-phenylpyridium ion (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which can induce Parkinson's syndrome, and MPTP were studied. Five groups of mice were given paraquat or MPTP orally: group 1, vehicle; groups 2 and 3, MPTP 0.3 and 20 mg/kg; groups 4 and 5, paraquat 0.07 and 0.36 mg/kg when 10 and 11 days old. Neonatal spontaneous motor activity was tested on Day 18 in mice given paraquat 0.36 mg/kg body wt. Adult spontaneous motor activity testing was performed at ages 60 and 120 days. On Day 125 the mice were decapitated and the contents of dopamine (DA), serotonin (5-HT), and metabolites in striatum were analyzed. The results may be summarized as follows: (1) No signs of acute toxicity or differences in weight gain were observed in any of the groups. Nor was any respiratory distress or motor performance dysfunction evident on Day 18 in mice given paraquat 0.36 mg/kg body wt. (2) The behavioral tests at 60 days of age showed a marked hypoactive condition in the mice given paraquat (at both doses) and MPTP (at both doses). (3) At the age of 120 days the hypoactive behavior persisted and appeared even more pronounced. (4) The high doses of MPTP and paraquat--and to a less extent the low doses--reduced the striatal content of DA and metabolites without affecting 5-HT. The altered behavior, together with the dose-dependent reduction of DA and metabolites in neostriata in this study, further demonstrates the susceptibility to low-dose exposure to environmental pollutants during the neonatal period.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D010269 Paraquat A poisonous dipyridilium compound used as contact herbicide. Contact with concentrated solutions causes irritation of the skin, cracking and shedding of the nails, and delayed healing of cuts and wounds. Methyl Viologen,Gramoxone,Paragreen A,Viologen, Methyl
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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