The multipotent role of metallothionein in the nervous system

Abstract

We provide a commentary on current experimental and theoretical advances and frame our consideration in terms of the possible functions of MT I+II in the nervous system. Metallothioneins (MT) are a family of small cysteine rich proteins, which since their discovery in 1957 have been implicated in a range of roles including toxic metal detoxification, protection against oxidative stress, and as a metallochaperone involved in the homeostasis of both zinc and copper. The most well studied member of the family is the mammalian metallothionein, which consists of two domains: a β-domain with 9 cysteine residues and an α-domain with 11 cysteine residues. Despite over half a century of research, the exact functions of MT in the nervous system are still unknown. Our studies have shown that the distribution of MT-I+II in the brain after prolonged intoxication, inhalation of 0.1% CdCl2 for 1 hour twice a week over 19 weeks, is dependent on the part of the brain. The metallothionein level declines more than 4 times in the hippocampus 3 weeks after continuous intoxication of 0.1% CdCl2. The level of MT-I+II in the cerebral cortex decreased by 1.5 times compared with the control group and did not change significantly in the cerebellum and thalamus/hypothalamus. The results of an experimental model of postoperative pain indicated that injection with MT-II prevents the development of postoperative hyperalgesia in response to mild alteration of physiological activity. Activation of locomotory and exploratory activity, and decrease of anxiety in rats under MT-II treatment at 100 µg/rat manifests itself on the 4th day after surgery. Our experimental data indicate the multipotent function of MT I+II in the rat brain both as a metal detoxifier and as an inhibitor of postoperative pain.