microRNA-132 regulates adult neural stem cells and their progeny to restore hippocampal neurogenesis and memory in Alzheimer’s disease

Hannah  Walgrave; Sriram  Balusu; Elke  Vanden Eynden; Katleen  Craessaerts; Nicky  Thrupp; Leen  Wolfs; Katrien  Horré; Yannick  Fourne; Alicja  Ronisz; Edina Silajdzic; Amber  Penning; Giorgia  Tosoni; Zsuzsanna  Callaerts-Vegh; Rudi  D’Hooge; Dietmar Rudolf  Thal; Henrik Zetterberg; Sandrine Thuret; Mark  Fiers; Carlo  Sala Frigerio; Bart De Strooper; Evgenia  Salta

microRNA-132 regulates adult neural stem cells and their progeny to restore hippocampal neurogenesis and memory in Alzheimer’s disease

Hannah Walgrave, Sriram Balusu, Elke Vanden Eynden, Katleen Craessaerts, Nicky Thrupp, Leen Wolfs, Katrien Horré, Yannick Fourne, Alicja Ronisz, Edina Silajdzic, Amber Penning, Giorgia Tosoni, Zsuzsanna Callaerts-Vegh, Rudi D’Hooge, Dietmar Rudolf Thal, Henrik Zetterberg, Sandrine Thuret, Mark Fiers, Carlo Sala Frigerio, Bart De StrooperEvgenia Salta

Basic and Clinical Neuroscience

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Abstract

Neural stem cells residing in the hippocampal neurogenic niche sustain life-long neurogenesis in the adult brain. Adult hippocampal neurogenesis (AHN) is functionally linked to mnemonic and cognitive plasticity in humans and rodents. In Alzheimer’s disease (AD), the process of generating new neurons at the hippocampal neurogenic niche is impeded, yet the mechanisms involved are unknown. Here we identify miR-132, one of the most consistently downregulated microRNAs in AD, as a potent regulator of AHN, exerting cell-autonomous pro-neurogenic effects in the adult neural stem cells and their progeny. Using distinct AD mouse models, cultured human primary and established neural stem cells, and human patient material, we demonstrate that AHN is directly impacted by AD pathology. miR-132 replacement in adult mouse AD hippocampus restores AHN and relevant memory deficits. Our findings corroborate the significance of AHN in AD and reveal the possible therapeutic potential of targeting miR-132 in neurodegeneration.

Original language	English
Journal	Cell Stem Cell
Publication status	Accepted/In press - 3 May 2021

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CELL-STEM-CELL-D-21-00186_R2Accepted author manuscript, 4.46 MBLicence: CC BY

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Walgrave, H., Balusu, S., Vanden Eynden, E., Craessaerts, K., Thrupp, N., Wolfs, L., Horré, K., Fourne, Y., Ronisz, A., Silajdzic, E., Penning, A., Tosoni, G., Callaerts-Vegh, Z., D’Hooge, R., Thal, D. R., Zetterberg, H., Thuret, S., Fiers, M., Sala Frigerio, C., ... Salta, E. (Accepted/In press). microRNA-132 regulates adult neural stem cells and their progeny to restore hippocampal neurogenesis and memory in Alzheimer’s disease. Cell Stem Cell.

@article{948b468864474ba9b59c447111e7a6bb,

title = "microRNA-132 regulates adult neural stem cells and their progeny to restore hippocampal neurogenesis and memory in Alzheimer{\textquoteright}s disease",

abstract = "Neural stem cells residing in the hippocampal neurogenic niche sustain life-long neurogenesis in the adult brain. Adult hippocampal neurogenesis (AHN) is functionally linked to mnemonic and cognitive plasticity in humans and rodents. In Alzheimer{\textquoteright}s disease (AD), the process of generating new neurons at the hippocampal neurogenic niche is impeded, yet the mechanisms involved are unknown. Here we identify miR-132, one of the most consistently downregulated microRNAs in AD, as a potent regulator of AHN, exerting cell-autonomous pro-neurogenic effects in the adult neural stem cells and their progeny. Using distinct AD mouse models, cultured human primary and established neural stem cells, and human patient material, we demonstrate that AHN is directly impacted by AD pathology. miR-132 replacement in adult mouse AD hippocampus restores AHN and relevant memory deficits. Our findings corroborate the significance of AHN in AD and reveal the possible therapeutic potential of targeting miR-132 in neurodegeneration.",

author = "Hannah Walgrave and Sriram Balusu and {Vanden Eynden}, Elke and Katleen Craessaerts and Nicky Thrupp and Leen Wolfs and Katrien Horr{\'e} and Yannick Fourne and Alicja Ronisz and Edina Silajdzic and Amber Penning and Giorgia Tosoni and Zsuzsanna Callaerts-Vegh and Rudi D{\textquoteright}Hooge and Thal, {Dietmar Rudolf} and Henrik Zetterberg and Sandrine Thuret and Mark Fiers and {Sala Frigerio}, Carlo and {De Strooper}, Bart and Evgenia Salta",

year = "2021",

month = may,

day = "3",

language = "English",

journal = "Cell Stem Cell",

issn = "1934-5909",

publisher = "Cell Press",

}

Walgrave, H, Balusu, S, Vanden Eynden, E, Craessaerts, K, Thrupp, N, Wolfs, L, Horré, K, Fourne, Y, Ronisz, A, Silajdzic, E, Penning, A, Tosoni, G, Callaerts-Vegh, Z, D’Hooge, R, Thal, DR, Zetterberg, H, Thuret, S, Fiers, M, Sala Frigerio, C, De Strooper, B & Salta, E 2021, 'microRNA-132 regulates adult neural stem cells and their progeny to restore hippocampal neurogenesis and memory in Alzheimer’s disease', Cell Stem Cell.

TY - JOUR

T1 - microRNA-132 regulates adult neural stem cells and their progeny to restore hippocampal neurogenesis and memory in Alzheimer’s disease

AU - Walgrave, Hannah

AU - Balusu, Sriram

AU - Vanden Eynden, Elke

AU - Craessaerts, Katleen

AU - Thrupp, Nicky

AU - Wolfs, Leen

AU - Horré, Katrien

AU - Fourne, Yannick

AU - Ronisz, Alicja

AU - Silajdzic, Edina

AU - Penning, Amber

AU - Tosoni, Giorgia

AU - Callaerts-Vegh, Zsuzsanna

AU - D’Hooge, Rudi

AU - Thal, Dietmar Rudolf

AU - Zetterberg, Henrik

AU - Thuret, Sandrine

AU - Fiers, Mark

AU - Sala Frigerio, Carlo

AU - De Strooper, Bart

AU - Salta, Evgenia

PY - 2021/5/3

Y1 - 2021/5/3

N2 - Neural stem cells residing in the hippocampal neurogenic niche sustain life-long neurogenesis in the adult brain. Adult hippocampal neurogenesis (AHN) is functionally linked to mnemonic and cognitive plasticity in humans and rodents. In Alzheimer’s disease (AD), the process of generating new neurons at the hippocampal neurogenic niche is impeded, yet the mechanisms involved are unknown. Here we identify miR-132, one of the most consistently downregulated microRNAs in AD, as a potent regulator of AHN, exerting cell-autonomous pro-neurogenic effects in the adult neural stem cells and their progeny. Using distinct AD mouse models, cultured human primary and established neural stem cells, and human patient material, we demonstrate that AHN is directly impacted by AD pathology. miR-132 replacement in adult mouse AD hippocampus restores AHN and relevant memory deficits. Our findings corroborate the significance of AHN in AD and reveal the possible therapeutic potential of targeting miR-132 in neurodegeneration.

AB - Neural stem cells residing in the hippocampal neurogenic niche sustain life-long neurogenesis in the adult brain. Adult hippocampal neurogenesis (AHN) is functionally linked to mnemonic and cognitive plasticity in humans and rodents. In Alzheimer’s disease (AD), the process of generating new neurons at the hippocampal neurogenic niche is impeded, yet the mechanisms involved are unknown. Here we identify miR-132, one of the most consistently downregulated microRNAs in AD, as a potent regulator of AHN, exerting cell-autonomous pro-neurogenic effects in the adult neural stem cells and their progeny. Using distinct AD mouse models, cultured human primary and established neural stem cells, and human patient material, we demonstrate that AHN is directly impacted by AD pathology. miR-132 replacement in adult mouse AD hippocampus restores AHN and relevant memory deficits. Our findings corroborate the significance of AHN in AD and reveal the possible therapeutic potential of targeting miR-132 in neurodegeneration.

M3 - Article

SN - 1934-5909

JO - Cell Stem Cell

JF - Cell Stem Cell

ER -

microRNA-132 regulates adult neural stem cells and their progeny to restore hippocampal neurogenesis and memory in Alzheimer’s disease

Abstract

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