Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice

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Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice. / Myhre, Christa Loth; Thygesen, Camilla; Villadsen, Birgitte; Vollerup, Jeanette; Ilkjaer, Laura; Krohn, Katrine Taekker; Grebing, Manuela; Zhao, Shuainan; Khan, Asif Manzoor; Dissing-Olesen, Lasse; Jensen, Morten Skovgaard; Babcock, Alicia A.; Finsen, Bente.

I: Frontiers in Cellular Neuroscience, Bind 13, 308, 07.2019.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Myhre, CL, Thygesen, C, Villadsen, B, Vollerup, J, Ilkjaer, L, Krohn, KT, Grebing, M, Zhao, S, Khan, AM, Dissing-Olesen, L, Jensen, MS, Babcock, AA & Finsen, B 2019, 'Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice', Frontiers in Cellular Neuroscience, bind 13, 308. https://doi.org/10.3389/fncel.2019.00308

APA

Myhre, C. L., Thygesen, C., Villadsen, B., Vollerup, J., Ilkjaer, L., Krohn, K. T., ... Finsen, B. (2019). Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice. Frontiers in Cellular Neuroscience, 13, [308]. https://doi.org/10.3389/fncel.2019.00308

CBE

Myhre CL, Thygesen C, Villadsen B, Vollerup J, Ilkjaer L, Krohn KT, Grebing M, Zhao S, Khan AM, Dissing-Olesen L, Jensen MS, Babcock AA, Finsen B. 2019. Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice. Frontiers in Cellular Neuroscience. 13. https://doi.org/10.3389/fncel.2019.00308

MLA

Vancouver

Myhre CL, Thygesen C, Villadsen B, Vollerup J, Ilkjaer L, Krohn KT o.a. Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice. Frontiers in Cellular Neuroscience. 2019 jul;13. 308. https://doi.org/10.3389/fncel.2019.00308

Author

Myhre, Christa Loth ; Thygesen, Camilla ; Villadsen, Birgitte ; Vollerup, Jeanette ; Ilkjaer, Laura ; Krohn, Katrine Taekker ; Grebing, Manuela ; Zhao, Shuainan ; Khan, Asif Manzoor ; Dissing-Olesen, Lasse ; Jensen, Morten Skovgaard ; Babcock, Alicia A. ; Finsen, Bente. / Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice. I: Frontiers in Cellular Neuroscience. 2019 ; Bind 13.

Bibtex

@article{ab252beb46dc46a18475978ddfb9f3ce,
title = "Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice",
abstract = "Insulin-like growth factor-1 (IGF-1) is a pleiotropic molecule with neurotrophic and immunomodulatory functions. Knowing the capacity of chronically activated microglia to produce IGF-1 may therefore show essential to promote beneficial microglial functions in Alzheimer's disease (AD). Here, we investigated the expression of IGF-1 mRNA and IGF-1 along with the expression of tumor necrosis factor (TNF) mRNA, and the amyloid-beta (A beta) plaque load in the hippocampus of 3- to 24-month-old APP(swe)/PS1(Delta E9) transgenic (Tg) and wild-type (WT) mice. As IGF-1, in particular, is implicated in neurogenesis we also monitored the proliferation of cells in the subgranular zone (sgz) of the dentate gyrus. We found that the A beta plaque load reached its maximum in aged 21- and 24 month-old APP(swe)/PS1(Delta E9) Tg mice, and that microglial reactivity and hippocampal IGF-1 and TNF mRNA levels were significantly elevated in aged APP(swe)/PS1(Delta E9) Tg mice. The sgz cell proliferation decreased with age, regardless of genotype and increased IGF-1/TNF mRNA levels. Interestingly, IGF-1 mRNA was expressed in subsets of sgz cells, likely neuroblasts, and neurons in both genotypes, regardless of age, as well as in glial-like cells. By double in situ hybridization these were shown to be IGF1 mRNA(+) CD11b mRNA(+) cells, i.e., IGF-1 mRNA-expressing microglia. Quantification showed a 2-fold increase in the number of microglia and IGF-1 mRNA-expressing microglia in the molecular layer of the dentate gyrus in aged APP(swe)/PS1(Delta E9) Tg mice. Double-immunofluorescence showed that IGF-1 was expressed in a subset of A beta plaque-associated CD11b(+) microglia and in several subsets of neurons. Exposure of primary murine microglia and BV2 cells to A beta(42) did not affect IGF-1 mRNA expression. IGF-1 mRNA levels remained constant in WT mice with aging, unlike TNF mRNA levels which increased with aging. In conclusion, our results suggest that the increased IGF-1 mRNA levels can be ascribed to a larger number of IGF-1 mRNA-expressing microglia in the aged APP(swe)/PS1(Delta E9) Tg mice. The finding that subsets of microglia retain the capacity to express IGF-1 mRNA and IGF-1 in the aged APP(swe)/PS1(Delta E9) Tg mice is encouraging, considering the beneficial therapeutic potential of modulating microglial production of IGF-1 in AD.",
keywords = "neuroinflammation, tumor necrosis factor, insulin-like growth factor, cerebral amyloidosis, aging, neurogenesis, TUMOR-NECROSIS-FACTOR, BETA-AMYLOID LOAD, ALZHEIMERS-DISEASE, MESSENGER-RNA, IGF-I, ACTIVATED MICROGLIA, GENE-EXPRESSION, DENTATE GYRUS, MOUSE MODELS, NEUROGENESIS",
author = "Myhre, {Christa Loth} and Camilla Thygesen and Birgitte Villadsen and Jeanette Vollerup and Laura Ilkjaer and Krohn, {Katrine Taekker} and Manuela Grebing and Shuainan Zhao and Khan, {Asif Manzoor} and Lasse Dissing-Olesen and Jensen, {Morten Skovgaard} and Babcock, {Alicia A.} and Bente Finsen",
year = "2019",
month = "7",
doi = "10.3389/fncel.2019.00308",
language = "English",
volume = "13",
journal = "Frontiers in Cellular Neuroscience",
issn = "1662-5102",
publisher = "Frontiers Media S.A",

}

RIS

TY - JOUR

T1 - Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice

AU - Myhre, Christa Loth

AU - Thygesen, Camilla

AU - Villadsen, Birgitte

AU - Vollerup, Jeanette

AU - Ilkjaer, Laura

AU - Krohn, Katrine Taekker

AU - Grebing, Manuela

AU - Zhao, Shuainan

AU - Khan, Asif Manzoor

AU - Dissing-Olesen, Lasse

AU - Jensen, Morten Skovgaard

AU - Babcock, Alicia A.

AU - Finsen, Bente

PY - 2019/7

Y1 - 2019/7

N2 - Insulin-like growth factor-1 (IGF-1) is a pleiotropic molecule with neurotrophic and immunomodulatory functions. Knowing the capacity of chronically activated microglia to produce IGF-1 may therefore show essential to promote beneficial microglial functions in Alzheimer's disease (AD). Here, we investigated the expression of IGF-1 mRNA and IGF-1 along with the expression of tumor necrosis factor (TNF) mRNA, and the amyloid-beta (A beta) plaque load in the hippocampus of 3- to 24-month-old APP(swe)/PS1(Delta E9) transgenic (Tg) and wild-type (WT) mice. As IGF-1, in particular, is implicated in neurogenesis we also monitored the proliferation of cells in the subgranular zone (sgz) of the dentate gyrus. We found that the A beta plaque load reached its maximum in aged 21- and 24 month-old APP(swe)/PS1(Delta E9) Tg mice, and that microglial reactivity and hippocampal IGF-1 and TNF mRNA levels were significantly elevated in aged APP(swe)/PS1(Delta E9) Tg mice. The sgz cell proliferation decreased with age, regardless of genotype and increased IGF-1/TNF mRNA levels. Interestingly, IGF-1 mRNA was expressed in subsets of sgz cells, likely neuroblasts, and neurons in both genotypes, regardless of age, as well as in glial-like cells. By double in situ hybridization these were shown to be IGF1 mRNA(+) CD11b mRNA(+) cells, i.e., IGF-1 mRNA-expressing microglia. Quantification showed a 2-fold increase in the number of microglia and IGF-1 mRNA-expressing microglia in the molecular layer of the dentate gyrus in aged APP(swe)/PS1(Delta E9) Tg mice. Double-immunofluorescence showed that IGF-1 was expressed in a subset of A beta plaque-associated CD11b(+) microglia and in several subsets of neurons. Exposure of primary murine microglia and BV2 cells to A beta(42) did not affect IGF-1 mRNA expression. IGF-1 mRNA levels remained constant in WT mice with aging, unlike TNF mRNA levels which increased with aging. In conclusion, our results suggest that the increased IGF-1 mRNA levels can be ascribed to a larger number of IGF-1 mRNA-expressing microglia in the aged APP(swe)/PS1(Delta E9) Tg mice. The finding that subsets of microglia retain the capacity to express IGF-1 mRNA and IGF-1 in the aged APP(swe)/PS1(Delta E9) Tg mice is encouraging, considering the beneficial therapeutic potential of modulating microglial production of IGF-1 in AD.

AB - Insulin-like growth factor-1 (IGF-1) is a pleiotropic molecule with neurotrophic and immunomodulatory functions. Knowing the capacity of chronically activated microglia to produce IGF-1 may therefore show essential to promote beneficial microglial functions in Alzheimer's disease (AD). Here, we investigated the expression of IGF-1 mRNA and IGF-1 along with the expression of tumor necrosis factor (TNF) mRNA, and the amyloid-beta (A beta) plaque load in the hippocampus of 3- to 24-month-old APP(swe)/PS1(Delta E9) transgenic (Tg) and wild-type (WT) mice. As IGF-1, in particular, is implicated in neurogenesis we also monitored the proliferation of cells in the subgranular zone (sgz) of the dentate gyrus. We found that the A beta plaque load reached its maximum in aged 21- and 24 month-old APP(swe)/PS1(Delta E9) Tg mice, and that microglial reactivity and hippocampal IGF-1 and TNF mRNA levels were significantly elevated in aged APP(swe)/PS1(Delta E9) Tg mice. The sgz cell proliferation decreased with age, regardless of genotype and increased IGF-1/TNF mRNA levels. Interestingly, IGF-1 mRNA was expressed in subsets of sgz cells, likely neuroblasts, and neurons in both genotypes, regardless of age, as well as in glial-like cells. By double in situ hybridization these were shown to be IGF1 mRNA(+) CD11b mRNA(+) cells, i.e., IGF-1 mRNA-expressing microglia. Quantification showed a 2-fold increase in the number of microglia and IGF-1 mRNA-expressing microglia in the molecular layer of the dentate gyrus in aged APP(swe)/PS1(Delta E9) Tg mice. Double-immunofluorescence showed that IGF-1 was expressed in a subset of A beta plaque-associated CD11b(+) microglia and in several subsets of neurons. Exposure of primary murine microglia and BV2 cells to A beta(42) did not affect IGF-1 mRNA expression. IGF-1 mRNA levels remained constant in WT mice with aging, unlike TNF mRNA levels which increased with aging. In conclusion, our results suggest that the increased IGF-1 mRNA levels can be ascribed to a larger number of IGF-1 mRNA-expressing microglia in the aged APP(swe)/PS1(Delta E9) Tg mice. The finding that subsets of microglia retain the capacity to express IGF-1 mRNA and IGF-1 in the aged APP(swe)/PS1(Delta E9) Tg mice is encouraging, considering the beneficial therapeutic potential of modulating microglial production of IGF-1 in AD.

KW - neuroinflammation

KW - tumor necrosis factor

KW - insulin-like growth factor

KW - cerebral amyloidosis

KW - aging

KW - neurogenesis

KW - TUMOR-NECROSIS-FACTOR

KW - BETA-AMYLOID LOAD

KW - ALZHEIMERS-DISEASE

KW - MESSENGER-RNA

KW - IGF-I

KW - ACTIVATED MICROGLIA

KW - GENE-EXPRESSION

KW - DENTATE GYRUS

KW - MOUSE MODELS

KW - NEUROGENESIS

U2 - 10.3389/fncel.2019.00308

DO - 10.3389/fncel.2019.00308

M3 - Journal article

C2 - 31417357

VL - 13

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

SN - 1662-5102

M1 - 308

ER -