Metallothioneins are highly expressed in astrocytes and microcapillaries in Alzheimer's disease

Zambenedetti, Pamela; Giordano, R; Zatta, Paolo

doi:10.1016/s0891-0618(98)00024-6

Cited by 79 publications

(49 citation statements)

References 25 publications

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“…Immunohistochemical identification of MT-I/II was carried out as previously described [21]. Briefly, a mixture of mouse monoclonal antibodies directed against MT-I/II (anti-MTs) (DAKO-MT, E9; DakoCytomation, Milan, Italy) was utilised.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Zatta

Raso

Zambenedetti³

et al. 2005

CMLS, Cell. Mol. Life Sci.

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Recent reports describe successful treatment using copper chelation therapy in neurodegenerative animal models. However, the success claimed for chelation therapy in neurodegenerative diseases is still rather controversial. To acquire new information on copper metabolism/homeostasis, we utilized cuprizone, a very sensitive and selective copper-chelating agent with well-known neurotoxic properties, as a relevant chemical model in mice. Upon cuprizone treatment, mice developed a pronounced astrocytosis, with brain oedema and spongiosis characterised by vacuolisations of the neuropil predominantly in the white matter. In addition, cuprizone treatment severely altered copper and zinc homeostasis in the central nervous system (CNS) as well as in all other tissues examined, with increasing metal ion concentrations particularly in the CNS. Concomitant with this increase in the Cu and Zn concentration in the brain, metallothionein-I and -II were also highly immunoreactive in astrocyte, consistent with the astrocytosis and demyelination observed in our and other laboratories.

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Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Zatta

Raso

Zambenedetti³

et al. 2005

CMLS, Cell. Mol. Life Sci.

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“…Thus, significant upregulation of these proteins has been observed in a number of human neurological diseases, including Alzheimer's disease (55,(79)(80)(81)(82)), Pick's disease (79), short-course Creutzfeld-Jakob disease (72), amyotrophic lateral sclerosis (83)(84)(85), and multiple sclerosis (86,87). Experiments carried out in animal models fully demonstrated the response of MT-1&2 to brain damage elicited by inflammatory factors such as lipopolysaccharides (11, 15, 24, 88), stress (62,(89)(90)(91), glutamate analogues (37,51,59,(92)(93)(94)(95), cryogenic injury (28,32,66,71), stroke/ischemia (17, [95][96][97][98], familial amyotrophic lateral sclerosis models (38,67,99,100), multiple sclerosis models (101)(102)(103), and gliotoxins (104)(105)(106).…”

Section: Transgenic Mice Show That Metallothionein-1and2 Are Essential mentioning

confidence: 99%

Metallothioneins and brain injury: What transgenic mice tell us

Hidalgo

2004

Environ Health Prev Med

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In rodents, the metallothionein (MT) family is composed of four members, MT-1 to MT-4. MT-1&2 are expressed in virtually all tissues including those of the Central Nervous System (CNS), while MT-3 (also called Growth Inhibitory Factor) and MT-4 are expressed prominently in the brain and in keratinizing epithelia, respectively. For the understanding of the physiological functions of these proteins in the brain, the use of transgenic mice has provided essential information. Results obtained in MT-1&2-null mice and in MT-1-overexpressing mice strongly suggest that these MT isoforms are important antioxidant, anti-inflammatory and antiapoptotic proteins in the brain. Results in MT-3-null mice show a very different pattern, with no support for MT-1&2-like functions. Rather, MT-3 could be involved in neuronal sprouting and survival. Results obtained in a model of peripheral nervous system injury also suggest that MT-3 could be involved in the control of nerve growth.

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“…Immobilization, immobilization with starvation, and food and water deprivation were applied as stress conditions to study the induction of MTs synthesis in rat brain. The regulation of MT expression in the brain is particularly interesting, since MT-I/II was found to be upregulated in Alzheimer's disease (Zambenedetti et al 2001), Binswanger's disease , and amyotrophic lateral sclerosis (ALS) (Hidalgo et al, 2002), as well as in aging (Mocchegiani et al, 2002a).…”

mentioning

confidence: 99%

“…Glial cells and astrocytes play a central role in the inflammatory phenomena that involve production of free radicals, particularly with a concomitant deficiency in antioxidants. In neurodegenerative diseases such as Alzheimer's, Binswanger's (Zambenedetti et al, 2001, and Down syndrome, where MTs are overexpressed, astrocyte activation represents a relevant marker. As described, treatment with darkness affects MT expression in specific areas in the following topographical order: corpus striatum, cerebellum, mesencephalon, hippocampus with fornix, parts of thalamus, and pons.…”

mentioning

confidence: 99%

Zn and Cu alteration in connection with astrocyte metallothionein I/II overexpression in the mouse brain upon physical stress

Beltramini

Pisa

Zambenedetti

et al. 2004

Glia

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The distribution of metallothioneins I/II in the mouse brain and their specific area distribution upon physical stress were studied. To induce physical stress, groups of mice were subjected to total darkness for different periods (2 weeks, 1 month, and 2 months). The concentration of metallothioneins, evaluated by immunohistochemistry, as well as area-specific protein expression, were found in the following quantitative order: corpus striatum, cerebellum, mesencephalon, hippocampus with fornix, parts of thalamus, and pons. All other brain areas were marginally affected, or even unaffected, in terms of immunopositive metallothionein reaction. Metallothionein I/II expression was compared with the immunopositivity of glial fibrillary acidic protein (GFAP). It is noteworthy that metallothioneins and GFAP are expressed in different types of astrocytes.

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Metallothioneins are highly expressed in astrocytes and microcapillaries in Alzheimer's disease

Cited by 79 publications

References 25 publications

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Metallothioneins and brain injury: What transgenic mice tell us

Zn and Cu alteration in connection with astrocyte metallothionein I/II overexpression in the mouse brain upon physical stress

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