Metallothionein-I and -III expression in animal models of Alzheimer disease

J Carrasco; P Adlard; C Cotman; A Quintana; M Penkowa; F Xu; W E Van Nostrand; J Hidalgo

doi:10.1016/j.neuroscience.2006.08.054

Metallothionein-I and -III expression in animal models of Alzheimer disease

J Carrasco, P Adlard, C Cotman, A Quintana, M Penkowa, F Xu, W E Van Nostrand, J Hidalgo

Institut for Neurovidenskab

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

58 Citationer (Scopus)

Abstract

Udgivelsesdato: 2006-Dec-28

Originalsprog	Engelsk
Tidsskrift	Neuroscience
Vol/bind	143
Udgave nummer	4
Sider (fra-til)	911-22
Antal sider	11
ISSN	0306-4522
DOI	https://doi.org/10.1016/j.neuroscience.2006.08.054
Status	Udgivet - 2006

Bibliografisk note

Keywords: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Astrocytes; Brain; Cerebral Cortex; Disease Models, Animal; Female; Gene Expression Regulation, Enzymologic; Glial Fibrillary Acidic Protein; Hippocampus; Male; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Mutation; Nerve Tissue Proteins; RNA, Messenger; Senile Plaques

Adgang til dokumentet

10.1016/j.neuroscience.2006.08.054

Citationsformater

@article{d6de46d0832a11de8bc9000ea68e967b,

title = "Metallothionein-I and -III expression in animal models of Alzheimer disease",

abstract = "Previous studies have described altered expression of metallothioneins (MTs) in neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and Alzheimer's disease (AD). In order to gain insight into the possible role of MTs in neurodegenerative processes and especially in human diseases, the use of animal models is a valuable tool. Several transgenic mouse models of AD amyloid deposits are currently available. These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta) deposition within the brain. We have evaluated the expression of MT-I and MT-III mRNA by in situ hybridization in three different transgenic mice models of AD: Tg2576 (carrying AbetaPP harboring the Swedish K670N/M671L mutations), TgCRND8 (Swedish and the Indiana V717F mutations), and Tg-SwDI (Swedish and Dutch/Iowa E693Q/D694N mutations). MT-I mRNA levels were induced in all transgenic lines studied, although the pattern of induction differed between the models. In the Tg2576 mice MT-I was weakly upregulated in cells surrounding Congo Red-positive plaques in the cortex and hippocampus. A more potent induction of MT-I was observed in the cortex and hippocampus of the TgCRND8 mice, likely reflecting their higher amyloid plaques content. MT-I upregulation was also more significant in Tg-SwDI mice, especially in the subiculum and hippocampus CA1 area. Immunofluorescence stainings demonstrate that astrocytes and microglia/macrophages surrounding the plaques express MT-I&II. In general, MT-I regulation follows a similar but less potent response than glial fibrillary acidic protein (GFAP) expression. In contrast to MT-I, MT-III mRNA expression was not significantly altered in any of the models examined suggesting that the various MT isoforms may have different roles in these experimental systems, and perhaps also in human AD.",

author = "J Carrasco and P Adlard and C Cotman and A Quintana and M Penkowa and F Xu and {Van Nostrand}, {W E} and J Hidalgo",

note = "Keywords: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Astrocytes; Brain; Cerebral Cortex; Disease Models, Animal; Female; Gene Expression Regulation, Enzymologic; Glial Fibrillary Acidic Protein; Hippocampus; Male; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Mutation; Nerve Tissue Proteins; RNA, Messenger; Senile Plaques",

year = "2006",

doi = "10.1016/j.neuroscience.2006.08.054",

language = "English",

volume = "143",

pages = "911--22",

journal = "Neuroscience",

issn = "0306-4522",

publisher = "Pergamon Press",

number = "4",

}

TY - JOUR

T1 - Metallothionein-I and -III expression in animal models of Alzheimer disease

AU - Carrasco, J

AU - Adlard, P

AU - Cotman, C

AU - Quintana, A

AU - Penkowa, M

AU - Xu, F

AU - Van Nostrand, W E

AU - Hidalgo, J

N1 - Keywords: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Astrocytes; Brain; Cerebral Cortex; Disease Models, Animal; Female; Gene Expression Regulation, Enzymologic; Glial Fibrillary Acidic Protein; Hippocampus; Male; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Mutation; Nerve Tissue Proteins; RNA, Messenger; Senile Plaques

PY - 2006

Y1 - 2006

N2 - Previous studies have described altered expression of metallothioneins (MTs) in neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and Alzheimer's disease (AD). In order to gain insight into the possible role of MTs in neurodegenerative processes and especially in human diseases, the use of animal models is a valuable tool. Several transgenic mouse models of AD amyloid deposits are currently available. These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta) deposition within the brain. We have evaluated the expression of MT-I and MT-III mRNA by in situ hybridization in three different transgenic mice models of AD: Tg2576 (carrying AbetaPP harboring the Swedish K670N/M671L mutations), TgCRND8 (Swedish and the Indiana V717F mutations), and Tg-SwDI (Swedish and Dutch/Iowa E693Q/D694N mutations). MT-I mRNA levels were induced in all transgenic lines studied, although the pattern of induction differed between the models. In the Tg2576 mice MT-I was weakly upregulated in cells surrounding Congo Red-positive plaques in the cortex and hippocampus. A more potent induction of MT-I was observed in the cortex and hippocampus of the TgCRND8 mice, likely reflecting their higher amyloid plaques content. MT-I upregulation was also more significant in Tg-SwDI mice, especially in the subiculum and hippocampus CA1 area. Immunofluorescence stainings demonstrate that astrocytes and microglia/macrophages surrounding the plaques express MT-I&II. In general, MT-I regulation follows a similar but less potent response than glial fibrillary acidic protein (GFAP) expression. In contrast to MT-I, MT-III mRNA expression was not significantly altered in any of the models examined suggesting that the various MT isoforms may have different roles in these experimental systems, and perhaps also in human AD.

AB - Previous studies have described altered expression of metallothioneins (MTs) in neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and Alzheimer's disease (AD). In order to gain insight into the possible role of MTs in neurodegenerative processes and especially in human diseases, the use of animal models is a valuable tool. Several transgenic mouse models of AD amyloid deposits are currently available. These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta) deposition within the brain. We have evaluated the expression of MT-I and MT-III mRNA by in situ hybridization in three different transgenic mice models of AD: Tg2576 (carrying AbetaPP harboring the Swedish K670N/M671L mutations), TgCRND8 (Swedish and the Indiana V717F mutations), and Tg-SwDI (Swedish and Dutch/Iowa E693Q/D694N mutations). MT-I mRNA levels were induced in all transgenic lines studied, although the pattern of induction differed between the models. In the Tg2576 mice MT-I was weakly upregulated in cells surrounding Congo Red-positive plaques in the cortex and hippocampus. A more potent induction of MT-I was observed in the cortex and hippocampus of the TgCRND8 mice, likely reflecting their higher amyloid plaques content. MT-I upregulation was also more significant in Tg-SwDI mice, especially in the subiculum and hippocampus CA1 area. Immunofluorescence stainings demonstrate that astrocytes and microglia/macrophages surrounding the plaques express MT-I&II. In general, MT-I regulation follows a similar but less potent response than glial fibrillary acidic protein (GFAP) expression. In contrast to MT-I, MT-III mRNA expression was not significantly altered in any of the models examined suggesting that the various MT isoforms may have different roles in these experimental systems, and perhaps also in human AD.

U2 - 10.1016/j.neuroscience.2006.08.054

DO - 10.1016/j.neuroscience.2006.08.054

M3 - Journal article

C2 - 17027170

SN - 0306-4522

VL - 143

SP - 911

EP - 922

JO - Neuroscience

JF - Neuroscience

IS - 4

ER -