Abstract
The objective of this study is to elucidate the primary action of methylmercury chloride (MMC) intoxication on peripheral nervous system. We chronologically observed the pathological changes of sciatic nerve, dorsal root ganglion (DRG) neurons, ventral and dorsal roots in rats given 4 mg/kg/day of MMC on consecutive days and killed on days 11, 15, 18 and 21. On day 11, an initial axonal degeneration of type B neuron occurred, predominantly in the distal portions of sciatic nerve. The DRG type A neuron was infiltrated by MRF-1-positive macrophages on day 11. Electron microscopy also demonstrated degenerated mitochondria in type A neuron. On day 21, most of type A neurons seemed to have disappeared. However, type B neurons were well preserved. Immunoblotting with monoclonal antibodies, P0 and neurofilament, demonstrated that both of proteins significantly decreases from day 15. In conclusion, these results indicate that the primary action on type A neuron is the neuron body that consequently results in an anterograde degeneration of nerve fibers, while the type B neuron degeneration occurs in a dying-back process in this subacute model. These findings suggest that the mechanisms involved in the degeneration induced by MMC vary and may depend on certain intrinsic factors peculiar to these neurons.
Similar content being viewed by others
References
Eto K (2000) Minamata disease. Neuropathology 20(Suppl):S14–S19
Takeuchi T, Eto K (1999) The pathology of Minamata disease: a tragic story of water pollution. Kyushu University Press Inc., Fukuoka
Eto K, Tokunaga H, Nagashima K, Takeuchi T (2002) An autopsy case of Minamata disease (Methylmercury poisoning)-pathological viewpoints of peripheral nerves. Toxicol Pathol 30:714–722
Takeuchi T, Eto K, Oyanagi S, Miyajima H (1978) Ultrastructural changes in human sural nerves in the neuropathology induced by intrauterine methylmercury poisoning. Virchows Arch B cell Pathol 27:137–154
Su M, Kakita A, Wakabayashi K et al (1997) Degeneration of spinal dorsal root ganglia in adult rats treated with methylmercury: chronological observations on the cell bodies, centrally directed axons and presynaptic terminals. Neuropathology 17:201–207
Jakobs JM, Carmichael N, Cavangh JB (1977) Ultrastructural changes in the nervous system of rabbits poisoned with methyl mercury. Toxicol Appl Pharmacol 39:249–261
Herman SP, Klein R, Talley FA, Krigman MR (1973) An ultrastructural study of methylmercury-induced primary sensory neuropathy in the rat. Lab Invest 28:104–118
Nagashima K, Fujii Y, Tsukamoto T et al (1996) Apoptosis process of cerebellar degeneration in experimental methylmercury intoxication of rats. Acta Neuropathol 91(1):71–77
Kobayashi Y, Sawa H, Akagi H, Itakura C et al (1998) Distributional pattern of apoptotic cells in rat cerebellar vermis experimentally induced by methylmercury intoxication. Neuropathology 18:33–37
Akagi H, Nishimura H (1991) Speciation of mercury in the environment. In: Imura N, Suzuki T, Clarkson TW (eds) Advances in methylmercury toxicology. Plenum Press, New York, pp 53–76
Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119:493–501
General concept of peripheral neuropathology (2000) In: Oh SJ (ed) Color atlas of nerve biopsy pathology. CRC Press, New York, p 4
Nagashima K (1997) A review of experimental methylmercury toxicity in rats: neuropathology and evidence for apoptosis. Toxicol Pathol 25(6):624–631
Papp H, Pakaski M, Kasa P (2002) Presenilin-1 and amyloid precursor protein are transported bidirectionally in the sciatic nerve of adult rat. Neurochem Int 41:429–435
Nihashi T, Inao S, Kajita Y, Kawai T et al (2001) Expression and distribution of beta amyloid precursor protein and beta amyloid peptide in reactive astrocytes after transient middle cerebral artery occlusion. Acta Neurochir 143:287–395
Tofaris GK, Patterson PH, Jessen KR, Mirsky R (2002) Degenerated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF. J Neurosci 22:6696–6703
Vogel DG, Margolis RL, Mottet NK (1985) The effect of methylmercury binding to microtubules. Toxicol Appl Pharmacol 80:473–486
Abe T, Haga T, Kurokawa M (1975) Blockage of axoplasmic transport and depolymerization of reassembled microtubules by methyl mercury. Brain Res 86:504–508
Sager PR, Doherty RA, Olmsted JB (1983) Interaction of methylmercury with microtubules in cultured cells and in vitro. Exp Cell Res 146:127–137
Roy C, Prasad KVS, Reuhl KR, Little JE, Valentine BK et al (1991) Taxol protects the microtubules of concanavalin A-activated lymphocytes from disassembly by methylmercury, but DNA synthesis is still inhibited. Exp Brain Res 195:345–352
Graff RD, Philbert MA, Lowndes HE, Reuhl KR (1993) The effect of glutathione depletion on methylmercury-induced microtubule disassembly in cultured embryonal carcinoma cells. Toxicol Appl Pharmacol 120:20–28
Bezerra R, de Oliveiraa WG, Luis Lealc D, Picanço-Dinizd W et al (2008) Three dimensional morphometric analyses of axon terminals early changes induced by methylmercury intoxication in the adult cat striate cortex. Brain Res 1244:155–163
Herculano AM, Crespo-López ME, Lima SMA et al (2006) Methylmercury intoxication activates nitric oxide synthase in chick retinal cell culture. Braz J Med Biol Res 39:415–418
Sakaue Motoharu, Takanaga Hiromi, Adachi Tatsumi et al (2003) Selective disappearance of an axonal protein, 440-kDa ankyrin B, associated with neuronal degeneration induced by methylmercury. J Neurosci Res 73:831–839
Sakamoto M, Nakano A, Kajiwara Y, Naruse I, Fujisaki T (1993) Effects of methyl mercury in postnatal developing rats. Environ Res 61:43–50
Castold AF, Coccini T (2001) Neurotoxicity and molecular effects of methylmercury. Brain Res Bull 55(2):197–203
Acknowledgments
We wish to express our gratitude to Dr. Yoshimura K and Dr. Tanaka Shuuitsu, in the Hokkaido University School of Medicine for they generously provided antibodies.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cao, B., Lv, W., Jin, S. et al. Degeneration of peripheral nervous system in rats experimentally induced by methylmercury intoxication. Neurol Sci 34, 663–669 (2013). https://doi.org/10.1007/s10072-012-1100-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10072-012-1100-3