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Neurotoxic Effects of 2,5-Hexanedione on Normal and Neurofilament-Deficient Quail

Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan, hirataku{at}vetmed.hokudai.ac.jp.

Makoto Mizutani

Nippon Institute for Biological Science, Kobuchizawa, Kitakomagun, Yamanashi 409-16, Japan

Takashi Kimura

Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan

Kenji Ochiai

Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan

Takashi Umemura

Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan

Chitoshi Itakura

Brain Science Institute, Institute of Physical and Chemical Research, Hirosawa, Wako, Saitama 351-0198, Japan

The neurotoxic effects of 2,5-hexanedione (2,5-HD) were investigated using neurofilament (NF)-deficient (Quv) Japanese quail in comparison with normal Japanese quail. Both Quv and normal Japanese quail were inoculated intraperitoneally with 350 mg/kg/day 2,5-HD for 6 consecutive wk. The results of 2,5-HD exposure differed substantially between the 2 strains of Japanese quail. The 2,5-HD-exposed normal quail showed leg paralysis about 4 wk after initiation of dosing. Some treated normal quail fell into dysstasia and died of nutritional disturbances. Histologically, 2,5-HD-treated normal quail had NF-rich axonal swellings and degeneration in the distal parts of the peripheral nerves, spinal cord, and cerebellar peduncles. In contrast, 2,5-HD-injected Quv quail showed tonic convulsion, ataxia gait, severe quivering, and excitation about 2-3 days after administration. Some treated Quv birds died immediately after systemic tonic convulsion, probably because of asphyxia. Although all treated Quv quail showed neurologic signs, there were no recognizable 2,5-HD-induced lesions in the nervous system. After about 4-6 wk of dosing, 2,5-HD induced distal axonopathy in normal quail and acute neurotoxicity in Quv quail.

Key Words: Axonal swelling • distal axonopathy • 2,5-hexanedione • Japanese quail • neurofilament • neurotoxicity • Quv quail

Toxicologic Pathology, Vol. 27, No. 3, 348-353 (1999)
DOI: 10.1177/019262339902700311


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