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

Authors

  • Sanna Lensu,

    Corresponding author
    1. 1 National Public Health Institute, Department of Environmental Health, P.O.B. 95, FI-70701 Kuopio, 2 Department of Pharmacology and Toxicology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 3Department of Neuroscience and 3Neurology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 4University Hospital of Kuopio, P.O.B. 1777, FI-70211 Kuopio, 5National Veterinary and Food Research Institute, Kuopio Department, P.O.B. 92, FI-70701 Kuopio, 6Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, University of Helsinki, P.O.B. 66, FI-00014 University of Helsinki, Finland
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  • 1,2 Riitta Miettinen,

    1. 1 National Public Health Institute, Department of Environmental Health, P.O.B. 95, FI-70701 Kuopio, 2 Department of Pharmacology and Toxicology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 3Department of Neuroscience and 3Neurology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 4University Hospital of Kuopio, P.O.B. 1777, FI-70211 Kuopio, 5National Veterinary and Food Research Institute, Kuopio Department, P.O.B. 92, FI-70701 Kuopio, 6Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, University of Helsinki, P.O.B. 66, FI-00014 University of Helsinki, Finland
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  • 3,4 Raimo Pohjanvirta,

    1. 1 National Public Health Institute, Department of Environmental Health, P.O.B. 95, FI-70701 Kuopio, 2 Department of Pharmacology and Toxicology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 3Department of Neuroscience and 3Neurology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 4University Hospital of Kuopio, P.O.B. 1777, FI-70211 Kuopio, 5National Veterinary and Food Research Institute, Kuopio Department, P.O.B. 92, FI-70701 Kuopio, 6Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, University of Helsinki, P.O.B. 66, FI-00014 University of Helsinki, Finland
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  • 5,6 Jere Lindén,

    1. 1 National Public Health Institute, Department of Environmental Health, P.O.B. 95, FI-70701 Kuopio, 2 Department of Pharmacology and Toxicology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 3Department of Neuroscience and 3Neurology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 4University Hospital of Kuopio, P.O.B. 1777, FI-70211 Kuopio, 5National Veterinary and Food Research Institute, Kuopio Department, P.O.B. 92, FI-70701 Kuopio, 6Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, University of Helsinki, P.O.B. 66, FI-00014 University of Helsinki, Finland
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  • and 6 Jouko Tuomisto 1

    1. 1 National Public Health Institute, Department of Environmental Health, P.O.B. 95, FI-70701 Kuopio, 2 Department of Pharmacology and Toxicology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 3Department of Neuroscience and 3Neurology, University of Kuopio, P.O.B. 1611, FI-70211 Kuopio, 4University Hospital of Kuopio, P.O.B. 1777, FI-70211 Kuopio, 5National Veterinary and Food Research Institute, Kuopio Department, P.O.B. 92, FI-70701 Kuopio, 6Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, University of Helsinki, P.O.B. 66, FI-00014 University of Helsinki, Finland
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  • * Part of this study was presented at the 10th International Congress of Toxicology, held in Tampere, Finland July 11–15, 2004.

Author for correspondence: Sanna Lensu, National Public Health Institute, Laboratory of Toxicology, P.O.B. 95, FI-70701 Kuopio, Finland (fax +358 17 201 265, e-mail sanna.lensu@ktl.fi).

Abstract

Abstract: 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 μg/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.

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