Figure 3. Potential mechanisms of MeHg-induced degeneration of motor efferents. MeHg leads to MN degeneration through Ca²⁺ mediated pathways.

Ionotrophic glutamate receptors NMDA and Ca²⁺ permeable AMPAR have been identified as important contributors to these alterations. However, studies in other cell types have shown that MeHg leads to increase glutamate release (1) and impaired function of excitatory amino acid transporter EAAT2 (impaired glutamate uptake) (2) which leads to increase glutamate in the synapse and could be contributing to the observed increased expression of NMDA receptors (3). These alterations could be contributing to the observed increase in [Ca²⁺]_i in lower MNs (4) as well as the alterations in synaptic transmission observed at the level of the neuromuscular junction (5). However, most of these observations have not been studied in MNs and should be the focus of future studies.