Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer's disease

被引：98

作者：

Walgrave, Hannah ^{[1
,2
]}

Balusu, Sriram ^{[1
,2
]}

Snoeck, Sarah ^{[3
]}

Vanden Eynden, Elke ^{[1
,2
]}

Craessaerts, Katleen ^{[1
,2
]}

Thrupp, Nicky ^{[1
,2
]}

Wolfs, Leen ^{[1
,2
]}

Horre, Katrien ^{[1
,2
]}

Fourne, Yannick ^{[1
,2
]}

Ronisz, Alicja ^{[2
,4
,5
]}

Silajdzic, Edina ^{[6
]}

Penning, Amber ^{[3
]}

Tosoni, Giorgia ^{[3
]}

Callaerts-Vegh, Zsuzsanna ^{[2
,7
]}

D'Hooge, Rudi ^{[2
,7
]}

Thal, Dietmar Rudolf ^{[2
,4
,5
]}

Zetterberg, Henrik ^{[8
,9
,10
,11
]}

Thuret, Sandrine ^{[6
]}

Fiers, Mark ^{[1
,2
]}

Frigerio, Carlo Sala ^{[11
]}

De Strooper, Bart ^{[1
,2
,11
]}

Salta, Evgenia ^{[3
]}

机构：

[1] VIB Ctr Brain & Dis Res, B-3000 Leuven, Belgium

[2] Katholieke Univ Leuven, Leuven Brain Inst, B-3000 Leuven, Belgium

[3] Netherlands Inst Neurosci, Lab Neurogenesis & Neurodegenerat, NL-1105 BA Amsterdam, Netherlands

[4] Katholieke Univ Leuven, Lab Neuropathol, B-3000 Leuven, Belgium

[5] UZ Leuven, Dept Pathol, B-3000 Leuven, Belgium

[6] Kings Coll London, Inst Psychiat, London SE5 9RX, England

[7] Katholieke Univ Leuven, Lab Biol Psychol, B-3000 Leuven, Belgium

[8] Sahlgrens Univ Hosp, Clin Neurochem Lab, S-43180 Molndal, Sweden

[9] UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England

[10] Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, S-43180 Molndal, Sweden

[11] UK Dementia Res Inst UCL, London WC1E 6BT, England

来源：

CELL STEM CELL | 2021年 / 28卷 / 10期

基金：

欧洲研究理事会; 欧盟地平线“2020”; 英国医学研究理事会;

关键词：

NEURAL PROGENITOR CELLS; PLURIPOTENT STEM-CELLS; LONG-TERM POTENTIATION; AMYLOID-BETA-PEPTIDE; NEUROPATHOLOGIC ASSESSMENT; PATTERN SEPARATION; DENTATE GYRUS; GRANULE CELLS; RNA-SEQ; NEURONS;

D O I：

10.1016/j.stem.2021.05.001

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Neural stem cells residing in the hippocampal neurogenic niche sustain lifelong 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 proneurogenic effects in 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 affected 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 mouse models of AD and reveal the possible therapeutic potential of targeting miR-132 in neurodegeneration.

引用

页码：1805 / +

页数：26

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