Research reportAnxiety-like behavior of young rats after 2-week zinc deprivation
Introduction
Zinc is essential for brain development and brain function [27]. Approximately 90% of the total brain zinc exists as zinc metalloproteins. Zinc has three functions in zinc metalloproteins: catalytic, coactive (or co-catalytic) and structural [36]. The rest is histochemically reactive, exists in the presynaptic vesicles and is stained by Timm's sulfide–silver method [9]. The presence of zinc-containing glutamatergic neurons that sequester zinc in the presynaptic vesicles and release it in a calcium- and impulse-dependent manner has been demonstrated in the brain, especially in the telencephalon [10].
Zinc homeostasis in the brain is strictly regulated by the brain barrier system, i.e., the blood–brain and blood–cerebrospinal fluid barriers, and is not easily affected by feeding a zinc-deficient diet [30], [31]. However, neuronal function is impaired by the feeding [13]. Learning and memory is impaired prior to the decrease in zinc concentration in the brain when experimental animals are fed a zinc-deficient diet. For example, zinc concentration in the brain of young adult rats is not decreased after 4-week zinc deprivation, whereas learning behavior of passive avoidance is impaired significantly [32]. On the other hand, impairment of spatial learning, memory or sensorimotor functions is not observed in zinc transporter-3-null mice, which lack the histochemically reactive zinc in synaptic vesicles [5]; zinc transporter-3-null mice have virtually no behavioral abnormality. Thus, the significance of zinc homeostasis in the brain in neuronal function is poorly understood.
Approximately 50% of the world population does not get adequate zinc [2]. Zinc deficiency in children is a nutritional and health problem in both developing and developed countries [12], [14], [19], [21], [25]. The evidence from experimental animals indicates that zinc deprivation during periods of rapid development critically impairs behavior and brain function, in addition to brain development [15], [16]. Lethargy (reduced activity and responsiveness) is a characteristic in zinc deficiency [13]. On the other hand, zinc supplementation improves neuropsychological behaviors in school-age children [20], [26]. It is possible that zinc function is also linked to the mental function. Metal diseases are an important issue in the world, especially in developed countries [18]. The mechanism of brain dysfunction in zinc deficiency is unclear and neuropsychological behavior in zinc deficiency also remains to be analyzed. Thus, the analysis on the relationship between neuropsychological behavior and neuronal function in zinc-deficient animals seems to be helpful to understand mental diseases, such as anxiety and depression.
Zinc concentration in the brain is not decreased in young rats fed a zinc-deficient diet for 2 weeks, whereas susceptibility to kainate-induced seizures is altered in the zinc-deficient young rats [35]. It is possible that intracellular free calcium (Ca2+) concentration is altered prior to the decrease in zinc concentration in the brain [34]. In the present study, intracellular free calcium concentration in the hippocampus and the behavior in the open-field and the plus-maze test were analyzed in the zinc-deficient young rats.
Section snippets
Chemicals
Control (44 mg Zn/kg) and zinc-deficient (2.7 mg Zn/kg) diets were purchased from Oriental Yeast Co. Ltd. (Yokohama, Japan). Artificial cerebrospinal fluid (ACSF) used as a perfusate was composed of 124 mM NaCl, 2.5 mM KCl, 2.0 mM CaCl2, 1.0 mM MgCl2, 1.25 mM NaH2PO4, 26 mM NaHCO3 and 10 mM d-glucose (pH 7.3).
Experimental animals
Male Wistar rats (3 weeks old) were purchased from Japan SLC (Hamamatsu, Japan). They were housed under the standard laboratory conditions (23 ± 1 °C, 55 ± 5% humidity) and had access to tap water and
Zinc, corticosterone, calcium levels in zinc deficiency
The mean body weights of rats, which were fed the zinc-deficient diet for 1 or 2 weeks, were 70.9 ± 4.3 g (5-week-old control, 104.5 ± 5.7 g) and 74.2 ± 4.0 g (6-week-old control, 128.8 ± 8.3 g), respectively. The increase in body weight was minimally observed in zinc-deficient group. Serum zinc concentration after 1-week zinc deprivation was decreased to less than 50% of that of the control rats (Fig. 1). However, extracellular zinc concentration in the hippocampus was not decreased even after 2-week zinc
Discussion
Total zinc concentration in the hippocampus is not decreased in young rats after 4-week zinc deprivation, whereas extracellular zinc concentration in the hippocampus is significantly decreased [33]. Timm's stain in the hippocampus is also decreased after 4-week zinc deprivation. Brain extracellular fluid and cerebrospinal fluid may be primary targets (compartments) to decrease zinc in zinc deficiency. However, zinc concentration in the hippocampal extracellular fluid is not decreased in young
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