Brain Metallothionein in Stress

Abstract

Brain metallothionein (MT) levels have been measured in the rat brain in basal and stress situations with polyclonal antibodies which do not cross-react significantly with the brain-specific MT isoform growth inhibitory factor (MT-III). Acute immobilization stress increases MT levels in most but not all brain areas. In contrast, chronic immobilization stress has no effect on MT levels. Although glucocorticoids and monoamines appear to have a role in brain MT regulation in control rats, they do not appear to have a vital role in stressed rats. Experiments with primary cultures enriched in neurons or astrocytes indicate that MT is present in both cell types and that responds to the well-known MT inducers zinc, copper and glucocorticoids.

Immunocytochemically detectable metallothionein is expressed by astrocytes in the ischaemic human brain

“…In vitro studies have also shown that astrocytes synthesize metallothioneins when exposed to cytokines and transitional metal ions [6,14,181. Current information about the cellular distribution of metallothionein in the CNS is limited to physiological changes [2,11,161 and little detailed information is available for reactive astrocytes in the human brain although metallothionein positive astrocytes have been described in Alzheimer's disease [15].…”

Effect of Stress on Mouse and Rat Brain Metallothionein I and III mRNA Levels

“…Certainly this is surprising given the known positive effect of glucocorticoids on the MT-I+II genes. Possible explanations have been dis cussed previously [16,29,34], and more work is in pro gress to add further insight into this paradoxical result. This is the first time that the effect of stress on brain MT-III has been evaluated.…”

“…Thus, slight increases were seen after 3 h of stress in hypothalamus, cerebellum and remaining brain (except hippocampus), which returned to basal levels after 8 h of stress. The small, transient increases of MT-I mRNA levels should, presumably, account for the small increases of the protein levels induced by stress [14,15,29], A more puzzling result is that obtained in the hippo campus, where a significant decrease of MT-I mRNA lev els was observed 3 h after the onset of stress, which returned to normal 5 h later (8 h of stress). This brain area is one where the effect of stress on MT-I+1I protein levels is not consistent through experiments, increasing them only occasionally [29], The transient decrease of MT-I mRNA levels could be related to such inconsistency, but more work is needed.…”

“…In previous studies, we have characterized to some extent the MT(-I+II) levels and MT response to stress in up to eight brain areas of the rat [14][15][16][17]29], and have concluded that stress has a general increasing effect on brain MT levels, although different sensitivities appear to exist in different areas [see 29 for further discussion]. The results for MT-I mRNA levels, despite the high variability that often precluded statistically significant results, were actually consistent with what is observed for the MT-I+II protein levels.…”

Absence of metallothionein-3 produces changes on MT-1/2 regulation in basal conditions and alters hypothalamic-pituitary–adrenal (HPA) axis

“…Although MT-1 was not one of these proteins, MT-3 could indirectly be an MT-1 regulator; on the basis of our results we are unable to declare a direct or indirect role of MT-3 in MT-1 regulation. Moreover, it is noticed that MT-1 and MT-2 genes are co-ordinately regulated in mice by metals and hormones such as glucocorticoids (Hidalgo et al, 1994b;Searle et al, 1984;Yagle and Palmiter, 1985) among other regulators. Since our results showed lower levels of corticosterone at basal conditions in Mt-3 KO mice, this may be one of the possible factors that could explain this decreased MT-I expression in the absence of MT-3.…”