Assessment by c-Fos immunostaining of changes in brain neural activity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leptin in rats.
The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes multiple effects in laboratory animals. One of these is a wasting syndrome (a dramatic loss of body weight over 2-5 weeks) whose mechanism is still largely unknown. We exploited the over 1000 times difference in TCDD sensitivity between Long-Evans (Turku/AB); (L-E) and Han/Wistar (Kuopio); (H/W) rats to reveal brain areas that might be activated by a single dose of TCDD (50 microg/kg) given 24 hr previously. Leptin (1.3 mg/kg intraperitoneally 2 hr before tissue harvest) was used as a reference compound, as its neural pathway for decreasing food intake in the control of energy homeostasis is fairly well known. Serial sections of the brains were immunostained with an antibody for the activity marker c-Fos, and selected areas -- primarily in the hypothalamus -- were analysed with a computer-assisted microscope. Given alone, TCDD did not elicit any major alterations in c-Fos protein levels in the hypothalamic nuclei at the early time-point studied (24 hr after administration), neither in pooled data nor in individual strains. The control substance leptin proved that the method is valid as it increased the number of c-Fos-immunopositive cells in the hypothalamic ventromedial and arcuate nuclei. Although the present findings are not suggestive of a primary role for the hypothalamus in the wasting syndrome, a time-course study covering also the feeding-active dark hours is warranted for their verification.
Lensu
Sanna
S
National Public Health Institute, Department of Environmental Health, P.O.B. 95, FI-70701 Kuopio, Finland. sanna.lensu@ktl.fi
Miettinen
Riitta
R
Pohjanvirta
Raimo
R
Lindén
Jere
J
Tuomisto
Jouko
J
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D013045:Species Specificity
D020738:Leptin; D000072317:Polychlorinated Dibenzodioxins; D016760:Proto-Oncogene Proteins c-fos