中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (4): 578-581.doi: 10.4103/1673-5374.247459

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

“老狗学会了新把戏”:针对正常和病理老化相关的认知能力下降的神经细胞外基质

  

  • 出版日期:2019-04-15 发布日期:2019-04-15

“Teaching old dogs new tricks”: targeting neural extracellular matrix for normal and pathological aging-related cognitive decline

Adam D. Richard, Xiao-Hong Lu   

  1. Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA, USA
  • Online:2019-04-15 Published:2019-04-15
  • Contact: Xiao-Hong Lu, MD, PhD, xlu1@lsuhsc.edu.
  • Supported by:

    The work is supported in part by National Alliance for Research on Schizophrenia & Depression (NARSAD) Young Investigator Grant from Brain Behavorial Research Foundation, No. 21365 (to XHL) and Ike Muslow Predoctoral Fellowship from Louisiana State University Health Sciences Center-Shreveport (to ADR).

摘要:

orcid: 0000-0002-2363-1708(Xiao-Hong Lu)

Abstract:

Cognitive decline is a feature of normal and pathological aging. As the proportion of the global aged population continues to grow, it is imperative to understand the molecular and cellular substrates of cognitive aging for therapeutic discovery. This review focuses on the critical role of neural extracellular matrix in the regulation of neuroplasticity underlying learning and memory in another under-investigated “critical period”: the aging process. The fascinating ideas of neural extracellular matrix forming a synaptic cradle in the tetrapartite synapse and possibly serving as a substrate for storage of very long-term memories will be introduced. We emphasize the distinct functional roles of diffusive neural extracellular matrix and perineuronal nets and the advantage of the coexistence of two structures for the adaptation to the ever-changing external and internal environments. Our study of striatal neural extracellular matrix supports the idea that chondroitin sulfate proteoglycan-associated extracellular matrix is restrictive on synaptic neuroplasticity, which plays important functional and pathogenic roles in early postnatal synaptic consolidation and aging-related cognitive decline. Therefore, the chondroitin sulfate proteoglycan-associated neural extracellular matrix can be targeted for normal and pathological aging. Future studies should focus on the cell-type specificity of neural extracellular matrix to identify the endogenous, druggable targets to restore juvenile neuroplasticity and confer a therapeutic benefit to neural circuits affected by aging.

Key words: aging, cognitive decline, neural extracellular matrix, tetrapartite synapse, long-term memory storage, therapeutic targeting, striatum, chondroitin sulfate proteoglycan