Time course of ultrastructural changes and immunoelectron microscopic localization of neurocalcin in motor endplates of the lumbrical muscles of rats given a single administration of 2,5-di(tert-butyl)-1,4-hydroquinone.
A time-course study of ultrastructural changes and immunoelectron microscopic localization of neurocalcin was performed on motor endplates of the lumbrical muscles of female Wistar rats given a single oral administration of 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ) at a dose of 120 mg/kg. Toxic signs such as salivation and muscle weakness of the hind legs appeared from 3 h after DTBHQ administration. No remarkable macroscopic or light microscopic changes were noted in the lumbrical muscles of the treated rats. At the ultrastructural level, neurotoxicity characterized by a decreases or loss of synaptic vesicles and mitochondria was observed after 24 h and at the 1-week time point, nerve endings had disappeared in some of the motor endplates, while many neurite nerve endings suggestive of early stage regeneration were apparent. After 6 weeks, newly formed reinnervated endplates were observed. Immunoelectron microscopically, the synaptic vesicle membranes were heavily labeled for neurocalcin in the control rats, but not at 24 h after DTBHQ treatment. Synaptic vesicle membranes in the DTBHQ group were weakly labeled at 1 week, but strongly at 6 weeks. The results strongly suggest that DTBHQ targets the motor endplates in the rat lumbrical muscles, causing depletion of neurocalcin in the synaptic vesicles followed by their loss.
Imazawa
T
T
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
Mitsumori
K
K
Kitajima
S
S
Onodera
H
H
Tamura
T
T
Takahashi
M
M
Hirose
M
M
D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D001284:Atrophy; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006873:Hydroquinones / Q000633:toxicity*; D016253:Microscopy, Immunoelectron; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009045:Motor Endplate / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000294:innervation* / Q000473:pathology; D009411:Nerve Endings / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D051596:Neurocalcin; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing; D013572:Synaptic Vesicles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D000975:Antioxidants; D002135:Calcium-Binding Proteins; D006873:Hydroquinones; D009419:Nerve Tissue Proteins; D051596:Neurocalcin; D044169:Receptors, Calcium-Sensing; C496690:Vsnl1 protein, rat; C019359:2,5-di-tert-butylhydroquinone