Decreased neurofilament density in large myelinated axons of metallothionein-I, II knockout mice

Metallothioneins (MTs) are small proteins, two isoforms (1, 11) of which bind metals. Their physiological role has been difficult to establish, but recent reports suggested that they serve an important function in nerve repair and in the protection against oxidative stress in the peripheral nervous system. We previously reported a decreased axon calibre in the large myelinated fibres of the phrenic nerve in the MT-I,II double knock out (MT-I, 11 KO) mouse model. We propose that this could be due to the effects of oxidative stress on neurofilaments (NFs). In this study, we examined the same subset of large myelinated axons using transmission electron microscopy (TEM). There was a decreased NF density in the axons of MT-I, 11 KO phrenic nerve (P < 0.005). This observation may have novel therapeutic implications in the treatment of amyotrophic lateral sclerosis (ALS), particularly as the terminal phases of the disease involve respiratory insufficiency. (c) 2006 Elsevier Ireland Ltd. All rights reserved.