Role of Wnt in the decline of oligodendrocyte generation in the ageing brain

Wnt 在衰老大脑少突胶质细胞生成下降中的作用

• 批准号: BB/M029379/1
• 负责人: Arthur Butt
• 金额: $ 45.83万
• 依托单位: University of Portsmouth
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM029379%2F1
• 关键词: Role; Wnt; decline; oligodendrocyte; generation

The massive computing power of the brain depends on the insulation of nerve cell connections with myelin sheaths, by cells known as oligodendrocytes (OLs). Bundles of these 'myelinated' connections form the white matter that is very prominent in the human cortex. Although a loss of cortical white matter and myelin has been documented in cognitive decline, the causes are unknown.There is evidence that OLs are continuously lost and regenerated from a pool of OL progenitors (OPs). For unknown reasons, the ability of OPs to generate OLs declines with age, which underlies the loss of myelin and cognitive functions. The applicant has identified a key factor that drives OL generation in the adult brain and which is deregulated in ageing. This factor is known as Wnt (pronounced wint), and the aim of this project is to determine the mechanisms by which Wnt controls OP generation and OL/myelin loss in the ageing mouse brain. This will provide new knowledge on the mechanisms underlying myelin loss in ageing brain and may ultimately lead to the identification of new cellular targets for protecting myelin and preserving cognitive function.This fundamental research fits the BBSRC Research Priority of 'Healthy ageing across the lifecourse'.

大脑强大的计算能力取决于神经细胞与髓鞘的绝缘，即少突胶质细胞 (OL)。这些“有髓鞘”连接束形成了在人类皮质中非常突出的白质。尽管认知能力下降会导致皮质白质和髓鞘质的丧失，但其原因尚不清楚。有证据表明，OL 会不断丢失，并从 OL 祖细胞 (OP) 库中再生。由于未知的原因，OP 生成 OL 的能力随着年龄的增长而下降，这是髓磷脂和认知功能丧失的基础。申请人已经确定了驱动成人大脑中 OL 生成并且在衰老过程中不受控制的关键因素。该因子被称为 Wnt（发音为 wint），该项目的目的是确定 Wnt 控制衰老小鼠大脑中 OP 生成和 OL/髓磷脂损失的机制。这将为衰老大脑中髓磷脂丧失的机制提供新的知识，并可能最终导致识别保护髓磷脂和维持认知功能的新细胞靶标。这项基础研究符合 BBSRC “整个生命周期健康老龄化”的研究重点。

项目成果

Agathisflavone protects neurons and drives promyelination through inducing switch of microglia M1 to a M2 profile and increasing purinoreceptors expression

Agathisflavone 通过诱导小胶质细胞 M1 转变为 M2 并增加嘌呤受体表达来保护神经元并驱动髓鞘形成

• 发表时间: 2019
• 期刊: GLIA
• 影响因子: 6.2
• 作者: De Almeida Carneiro M. M. A.

Targeting the Subventricular Zone to Promote Myelin Repair in the Aging Brain.

靶向室内区域以促进衰老大脑的髓磷脂修复。

• DOI: 10.3390/cells11111809
• 发表时间: 2022-05-31
• 期刊: CELLS
• 影响因子: 6
• 作者: Butt, Arthur Morgan;Rivera, Andrea Dominico;Fulton, Daniel;Azim, Kasum
• 通讯作者: Azim, Kasum

Metabotropic Glutamate Receptors Protect Oligodendrocytes from Acute Ischemia in the Mouse Optic Nerve.

• DOI: 10.1007/s11064-017-2220-1
• 发表时间: 2017-09
• 期刊: Neurochemical research
• 影响因子: 4.4
• 作者: Butt AM;Vanzulli I;Papanikolaou M;De La Rocha IC;Hawkins VE
• 通讯作者: Hawkins VE

Accelerated Dystrophy and Decay of Oligodendrocyte Precursor Cells in the APP/PS1 Model of Alzheimer's-Like Pathology.

阿尔茨海默氏病病理学的APP/PS1模型中的少突胶质细胞前体细胞的加速营养不良和衰减。

• DOI: 10.3389/fncel.2020.575082
• 发表时间: 2020
• 期刊: Frontiers in cellular neuroscience
• 影响因子: 5.3
• 作者: Chacon-De-La-Rocha I;Fryatt G;Rivera AD;Verkhratsky A;Raineteau O;Gomez-Nicola D;Butt AM
• 通讯作者: Butt AM

Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity.

• DOI: 10.1371/journal.pbio.2000698
• 发表时间: 2017-03
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Azim K;Angonin D;Marcy G;Pieropan F;Rivera A;Donega V;Cantù C;Williams G;Berninger B;Butt AM;Raineteau O
• 通讯作者: Raineteau O