Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.
Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.
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DOI：
10.18632/aging.101256
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发表时间：
2017-06-28
期刊：
影响因子：
--
通讯作者：
Kwok JCF
中科院分区：
文献类型：
--
作者：
Foscarin S;Raha-Chowdhury R;Fawcett JW;Kwok JCF
来自中枢神经系统（CNS）的神经周围网络（PNNs）中的硫酸软骨素（CS）蛋白聚糖参与可塑性和记忆的控制。在阿尔茨海默病和衰老模型中，去除pnn可重新激活可塑性并恢复记忆。它们的作用依赖于CS蛋白聚糖的糖胺聚糖（GAG）链，主要在4 （C4S）或6 （C6S）位置被硫酸化。C4S具有抑制作用，而C6S更有利于轴突的生长、再生和可塑性。临界期闭合时C6S减小。我们询问CS-GAG硫酸化是否与老年大鼠的记忆丧失有关。免疫组化显示C4S在3 ~ 18个月进行性升高，C6S下降。从脑pnn中提取的GAGs在12个月和18个月时显示C6S显著降低，C4S/C6S比值升高。软骨素硫转移酶mRNA水平无显著变化。与来自弥漫性细胞外基质的gag相比，PNN gag对轴突生长的抑制作用更大。18个月的PNN GAGs比3个月的PNN GAGs具有更强的抑制作用。我们认为，老年大脑中PNN GAG硫酸化的变化使PNN更具抑制性，从而导致可塑性下降并对记忆产生不利影响。
Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimer’s disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains of CS proteoglycans, which are mainly sulfated in the 4 (C4S) or 6 (C6S) positions. While C4S is inhibitory, C6S is more permissive to axon growth, regeneration and plasticity. C6S decreases during critical period closure. We asked whether there is a late change in CS-GAG sulfation associated with memory loss in aged rats. Immunohistochemistry revealed a progressive increase in C4S and decrease in C6S from 3 to 18 months. GAGs extracted from brain PNNs showed a large reduction in C6S at 12 and 18 months, increasing the C4S/C6S ratio. There was no significant change in mRNA levels of the chondroitin sulfotransferases. PNN GAGs were more inhibitory to axon growth than those from the diffuse extracellular matrix. The 18-month PNN GAGs were more inhibitory than 3-month PNN GAGs. We suggest that the change in PNN GAG sulfation in aged brains renders the PNNs more inhibitory, which lead to a decrease in plasticity and adversely affect memory.
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影响因子：
4.8
作者：
Dick, Gunnar;Tan, Chin Lik;Kwok, Jessica C. F.
通讯作者：
Kwok, Jessica C. F.
影响因子：
16.2
作者：
Donato, Flavio;Chowdhury, Ananya;Caroni, Pico
通讯作者：
Caroni, Pico
DOI：
10.1007/978-1-4939-0777-9_10
发表时间：
2014-01-01
期刊：
AXON GROWTH AND REGENERATION: METHODS AND PROTOCOLS
影响因子：
--
作者：
Kwok, Jessica C. F.;Heller, Janosch P.;Fawcett, James W.
通讯作者：
Fawcett, James W.
影响因子：
3.3
作者：
Giamanco, K. A.;Matthews, R. T.
通讯作者：
Matthews, R. T.
影响因子：
2.5
作者：
Carulli, Daniela;Rhodes, Kate E.;Fawcett, James W.
通讯作者：
Fawcett, James W.