Cellular neuroscienceMetallothionein-I and -III expression in animal models of Alzheimer disease
Section snippets
AD amyloid deposits mouse models
Tg2576 male mice (Hsiao et al., 1996) were purchased from Taconic Europe A/S (Ry, Denmark), and crossed with C57BL/6 females; female offspring 14–18 months old were used in this study (n=9 APP+/−, n=12 APP−/−). TgCRND8 male and female mice (Chisthi et al., 2001), courtesy of David Westaway (University of Toronto), were maintained on a B6C3F1/J genetic background and used at 18 months of age along age- and gender-matched controls (n=3 in the four groups). Tg-SwDI male mice (Davis et al., 2004)
Results
Fig. 1 shows representative autoradiographies for MT-I, MT-III and GFAP in situ hybridizations obtained in the Tg2576 AD model. Fig. 2 shows representative microautoradiographies. It is quite clear that, as expected, GFAP was prominently upregulated in areas surrounding amyloid plaques, which were abundantly present in the cortex and hippocampus. Quantifications carried out in the autoradiographic films in both areas demonstrated highly significant (P<0.01) increases in GFAP mRNA levels (Table 1
Discussion
Alzheimer disease, the major human neurodegenerative disease, is a progressive neurodegenerative disease of the CNS. AD is characterized by senile plaques, neurofibrillary tangles and neuronal loss. MT-I&II have consistently been shown to be upregulated in AD brains; considering what is known in several animal models of brain injury (Hidalgo et al., 2001), one could envision this response as a neuroprotective mechanism, but to test this in AD patients will be a formidable task. MT-III, on the
Acknowledgments
Support by the Ministerio de Ciencia y Tecnología and Feder (SAF2002-01268) and Ministerio de Educación y Ciencia and Feder SAF2005-00671 (J.H.) and NIH grant NS36645 (W.E.V.N.) is fully acknowledged. The support of the Lundbeck Foundation, IMK Almene Fond, Vera og Carl Michaelsens Legat, Kathrine og Vigo Skovgaards Fond, Scleroseforeningen, Karen A Tolstrup, Hørslev-fonden, Toyota Fonden, Dir. Leo Nielsens Legat, the Danish Medical Association Research Fund, the Wacherhausens Legat, Grosserer
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2022, Brain, Behavior, and ImmunityCitation Excerpt :A protective role for Mt1 and Mt2 has been suggested in mouse models for focal cerebral ischemia where lack of Mt1 and Mt2 expression was shown to exacerbate brain damage (Trendelenburg et al., 2002), while overexpression of Mt1 was shown to improve motor behavior and reduce lesion size (van Lookeren Campagne et al., 1999). In several neurodegenerative disorders, including AD, MT1 and MT2 are upregulated (Adlard et al., 1998; Duguid et al., 1989; Zambenedetti et al., 1998) and associated with Aβ plaques in several AD animal models (Carrasco et al., 2006; Hidalgo et al., 2006). The upregulation of MTs could have a neuroprotective function against the oxidative stress and neuroinflammation involved in AD pathogenesis (Adlard et al., 1998; Nunomura et al., 2006).
Molecular aspects of metallothioneins in dementias
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2019, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesCitation Excerpt :Its role in AD disease is still under study: this protein has been generally reported down-expressed in relation to AD although data are still controversial [48]. Expression studies on MT-III in AD model mice brain, showed a slight upregulation in Tg2576 genotype but no in TgCRND8 and Tg-SwDI mice [49]. Other studies in Tg2576 mice conversely reported decreased levels of MT-III, hypothesizing its possible role in the disease and target therapeutic potential [50,51].
Metal Transporters in Neurodegeneration
2017, Biometals in Neurodegenerative Diseases: Mechanisms and TherapeuticsExposure to ambient ultrafine particulate matter alters the expression of genes in primary human neurons
2017, NeuroToxicologyCitation Excerpt :Although the mechanism is not clearly understood, prolonged elevated MTI/MTII expression in the brain has been consistently shown to be correlated with the onset and progression of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and motor neuron disease (Manso et al., 2011; Stankovic et al., 2007). In the case of AD, animal studies support the hypothesis that there is an interaction between MTI/II induction and amyloid-beta deposition (Carrasco et al., 2006). Future studies are needed to determine whether the prolonged induction of MT1A and MT1F isoforms by PM specifically contributes to the progression of AD or is a secondary protective response triggered by the underlying pathology.
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Javier Carrasco and Paul Adlard contributed equally to this paper.