Downregulation of brain-derived neurotrophic factor mRNA in adult rat brain after acute administration of methylmercury.
Conventionally, assessment of the neurotoxicity of environmental pollutants relies on high-dosage treatment and nonspecific end points. In the present study, the early temporal and regional alterations in the mRNAs of neurotrophins were investigated following subtoxic doses of methylmercury (MeHg) in adult Sprague-Dawley rats using in situ hybridization histochemistry and phosphoimaging evaluation. Decreases in brain-derived neurotrophic (BDNF) mRNA labeling intensities were seen in the dentate gyrus (DG; 44% of controls), and in the CA1 (72% of controls) and CA3c (70% of controls) cell layers of hippocampus after 8 mg MeHg/kg (ip) at 4 h, and at 1 h only in the DG. The decrease in BDNF mRNA expression in the DG was dose-dependent. At 3 d, regional levels had recovered. No significant changes could be detected in mRNA levels of the BDNF high-affinity receptor trkB or neurotrophin-3 mRNA at either 1 h, 4 h, or 3 d. Cresyl violet staining and GFAP immunohistochemistry did not reveal any major neuropathology in hippocampus at 2 wk. Thus, MeHg causes specific downregulation of BDNF mRNA, unlike many other perturbations of central nervous system homeostasis that have been shown to lead to upregulation of this mRNA.
Andersson
H
H
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Lindqvist
E
E
Olson
L
L
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D015342:DNA Probes; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008767:Methylmercury Compounds / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000096:biosynthesis; D020933:Neurotrophin 3; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis
D019208:Brain-Derived Neurotrophic Factor; D015342:DNA Probes; D005904:Glial Fibrillary Acidic Protein; D008767:Methylmercury Compounds; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases