Perineuronal and perisynaptic extracellular matrix in the human spinal cord

Area of Science:

• Neuroscience
• Histology
• Biochemistry

Background:

• The extracellular matrix (ECM) plays a crucial role in the central nervous system (CNS), but its composition in the spinal cord is understudied.
• Understanding spinal cord ECM is vital for neuropathology, regeneration, and CNS repair strategies, especially concerning chondroitin sulphate proteoglycans (CSPGs).
• Previous research has focused more on brain ECM, leaving a knowledge gap regarding the spinal cord's specific matrix architecture.

Purpose of the Study:

• To provide the first detailed description and systematic mapping of major ECM components throughout the human spinal cord.
• To investigate the distribution of aggrecan, brevican, proteoglycan link-protein, tenascin-R, and hyaluronan in both grey and white matter.
• To characterize ECM associations with specific neuronal populations and afferent types in the human spinal cord.

Main Methods:

• Analysis of two post-mortem human spinal cord specimens.
• Systematic immunohistochemical mapping of key ECM components, including aggrecan, brevican, proteoglycan link-protein, tenascin-R, and hyaluronan.
• Exemplary investigation of other proteoglycans like versican, neurocan, and NG2 in specific regions.
• Multiple immunolabelling techniques to identify ECM associations with neuronal types and synapses.

Main Results:

• Tenascin-R and hyaluronan are present in both white and grey matter of the human spinal cord.
• Aggrecan, proteoglycan link-protein, and brevican are predominantly restricted to the grey matter.
• Aggrecan forms perineuronal nets in ventral and lateral horns, while link-protein and brevican form axonal coats (ACs) in most grey matter regions.
• Perineuronal nets are associated with projection neurons, including motorneurons and spinocerebellar tract neurons.
• Nociceptive afferents lack distinct ECM assemblies, unlike glycinergic or GABAergic synapses.

Conclusions:

• This study provides a comprehensive map of ECM distribution in the human spinal cord, differentiating grey and white matter components.
• The findings reveal specific ECM structures like perineuronal nets and axonal coats and their association with neuronal types.
• This detailed ECM characterization is essential for advancing clinical strategies in spinal cord injury, repair, and regenerative therapies.