Effect of Zinc Deficiency on the Behavior of Metallothionein-I, II Knockout Mice

摘要

Zinc is believed to modulate neurotransmitters such as glutamate and GABA in the central nervous system (CNS). Metallothioneins (MTs) aid in heavy metal metabolism and detoxification, and protect CNS cells from numerous pathologies. However, little is known about neurobehavioral significance of MTs or their relationship with zinc. To understand the effect of MT-I and MT-II (MT-I, II) on behavioral function and to elucidate the relationship between zinc and MT-I, II, we performed neurobehavioral tests on female MT-I, II knockout mice established from a 129/Sv strain (MT null) and their control (wild-type) counterparts. Five-week-old mice of both strains were divided into two groups of zinc-deficient (Zn-) or -supplemented (Zn+) diet. Four weeks after initiating the experimental diet, the following tests were performed : measurement of 24-h spontaneous motor activities, open-field test, and Morris water maze. Growth of both strains was suppressed by feeding the mice with a Zn- diet. We observed lower zinc levels in the liver and kidney in both MT null groups with no significant difference between mice strains. Various spontaneous activity patterns were observed between MT null and wild-type (WT) mice. In the first phase of the Morris water maze, zinc deficiency caused significantly prolonged latency in the MT null mice. Nearly identical decreases in brain zinc levels were observed in MT null and WT mice after consuming the Zn- diet, and treatment of Zn deficiency in MT null mice impaired the formation of spatial learning memory. These findings suggest that MT-I, II play a role in modulating behavioral activities, and that zinc is essential for the spatial cognitive function of MTs.