Aluminum exposure decreases dopamine D1 and D2 receptor expression in mouse brain.
Aluminum (Al) has been identified as a potential contributing factor in the etiology of several neurodegenerative disorders, but data regarding specific effects on neurotransduction, especially on dopaminergic neurotransduction, are lacking. The objective of this study was to determine the extent of expressional alterations in dopamine receptors (DRs) in two dopaminergic subtypes, D1 and D2, in low and high dose Al-treated mice. After administration of Al (four intraperitoneal injections of 30 or 60 mg/kg AlCl3.6H2O at 2 h intervals), expression of the dopamine D1-like and D2-like receptors (DRD1, DRD2) was examined in the cortex and striatum of mouse brain at bregma levels of 1.10, -0.10 and -1.34 mm. In the cortex, Al treatment decreased densities of DRD1 and DRD2 in a dose-dependent manner at all three bregma levels, especially in the high-dose Al group. Similarly, DRD1 and DRD2 expression in the striatum also exhibited dose dependency and statistically significant decreases were seen in the high-dose group, except in the striatum at bregma level - 1.34. These findings suggest that DR in the caudal striatum is more resistant to the effects of Al exposure than DR in the cortex or rostral striatum. In addition, our results suggest that disturbance of dopaminergic neurotransmission mediated by DRD1 and/or DRD2 may be involved in the pathogenesis of Al neurotoxicity.
Kim
Sunyoun
S
Department of Safety Evaluation, Biotoxtech Company, Chungbuk 363-883, Korea.
Nam
Jungmin
J
Kim
Kisok
K
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002712:Chlorides / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism
D017607:Aluminum Compounds; D002712:Chlorides; D004785:Environmental Pollutants; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000077410:Aluminum Chloride