Neonatal primary neuronal death induced by capsaicin and axotomy involves an apoptotic mechanism.
To clarify the mechanism of capsaicin-induced primary neuronal cell death, newborn and adult rats were given a subcutaneous injection of capsaicin (50 mg/kg). Neonatal capsaicin injection induced neuronal apoptosis in the trigeminal ganglion. Apoptotic neurons had peripheral stacks of long parallel endoplasmic reticulum that are characteristic to primary neurons of the B-type, and exhibited nucleoplasmic condensation, nuclear shrinkage and cytoplasmic fragmentation. Light microscopically, apoptotic neurons exhibited a sign of DNA fragmentation as revealed by a nick end labelling method. The proportion of apoptotic cells was quite low during the first 12 h after capsaicin injection (<1%), rapidly increase to 10.44% by 24 h, and decreased to 0.29% by 48 h. Normal and vehicle control levels of apoptosis were <1%. Nerve growth factor (NGF, 0.5 mg/kg) simultaneously administered with capsaicin reduced the incidence of apoptosis by about 35% at 24 h post-injection. Neonatal transection of the infraorbital nerve induced neuronal apoptosis similar to that produced by the neonatal capsaicin in the maxillary division of the trigeminal ganglion. Unlike capsaicin, however, the neurotomy-induced apoptosis was seen in neurons of both the A- and B-types. Neither the capsaicin injection nor the neurotomy induced apoptosis in adult rats, though mitochondrial swelling similar to that seen at 0.5 h after neonatal capsaicin was observed after capsaicin injection in adults. The results indicate that the capsaicin-induced and nerve injury-induced primary neuronal damages in newborn rats share a common final pathway, apoptosis.
Department of Oral Anatomy II, Okayama University Dental School, 2-5-1 Shikata-cho, Okayama 700, Japan. tsugi@dent.okayama-u.ac.jp
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Sugimoto
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Xiao
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Ichikawa
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D019771:Axotomy; D002211:Capsaicin / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D020287:In Situ Nick-End Labeling; D007279:Injections, Subcutaneous; D008297:Male; D008854:Microscopy, Electron; D009414:Nerve Growth Factors / Q000172:deficiency; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D009414:Nerve Growth Factors; D002211:Capsaicin