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Degeneration of peripheral nervous system in rats experimentally induced by methylmercury intoxication
Bingzhen Cao1, Wei Lv, Shan Jin
1Department of Neurology, Jinan General Military Hospital, Shifan street 25, Jinan 250031, China. cbzxia2011@163.com
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.
Insights
Methylmercury chloride (MMC) causes distinct nerve damage. Type A neurons undergo primary cell body damage leading to nerve fiber degeneration, while Type B neurons show a dying-back process.
Area of Science:
- Neuroscience
- Toxicology
- Pathology
Background:
- Methylmercury chloride (MMC) is a known neurotoxin.
- Understanding its specific mechanisms of action on the peripheral nervous system is crucial.
Purpose of the Study:
- To elucidate the primary action of methylmercury chloride (MMC) intoxication on the peripheral nervous system.
- To chronologically observe pathological changes in rat sciatic nerve, dorsal root ganglion (DRG) neurons, and nerve roots following MMC exposure.
Main Methods:
- Rats were administered 4 mg/kg/day of MMC and sacrificed on days 11, 15, 18, and 21.
- Pathological changes were assessed in the sciatic nerve, DRG neurons, and nerve roots.
- Techniques included light microscopy, electron microscopy, and immunoblotting with monoclonal antibodies (P0 and neurofilament).
Main Results:
- Axonal degeneration of Type B neurons was observed initially in distal sciatic nerve portions by day 11.
- Type A DRG neurons showed macrophage infiltration and mitochondrial degeneration by day 11, with most disappearing by day 21.
- P0 and neurofilament protein levels significantly decreased from day 15 onwards.
Conclusions:
- MMC primarily targets the cell body of Type A neurons, causing anterograde nerve fiber degeneration.
- Type B neuron degeneration follows a dying-back process in this subacute model.
- The varying degeneration mechanisms suggest intrinsic neuronal factors influence MMC-induced neurotoxicity.
