Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 10; pp. 2420 - 2434
• Main Authors: Miyata, Shinji, Kitagawa, Hiroshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2017
• Subjects: Animals; Axon regeneration; brain; Brain - metabolism; Brain - physiology; Brain - physiopathology; Brain Chemistry; Brain Injuries - metabolism; Brain Injuries - pathology; Brain Injuries - physiopathology; Brain Injuries - rehabilitation; chondroitin sulfate; Chondroitin sulfate proteoglycan; Chondroitin Sulfates - chemistry; Chondroitin Sulfates - metabolism; dendrites; extracellular matrix; Extracellular Matrix - chemistry; Extracellular Matrix - metabolism; Humans; Hyaluronan; hyaluronic acid; Hyaluronic Acid - chemistry; Hyaluronic Acid - metabolism; Nerve Net - physiology; Nerve Net - physiopathology; Nerve Regeneration - physiology; nerve tissue; Neurogenesis - physiology; Neuronal Plasticity - physiology; Neurons - cytology; Neurons - physiology; Parvalbumin-expressing inhibitory neuron; Parvalbumins - genetics; Parvalbumins - metabolism; Perineuronal net; synapse; Synapses - physiology; Synaptic plasticity; Hyaluronan; Chondroitin sulfate proteoglycan; Axon regeneration; Perineuronal net; Synaptic plasticity; Parvalbumin-expressing inhibitory neuron
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.06.010

The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration. Here, we review recent progress in understanding of the molecular basis of organization and remodeling of the brain ECM, and the involvement of several types of experience-dependent neural plasticity, with a particular focus on the mechanism that regulates PV cell function through specific interactions between CS chains and their binding partners. We also discuss how the barrier function of the brain ECM restricts dendritic spine dynamics and limits axon regeneration after injury. The brain ECM not only forms physical barriers that modulate neural plasticity and axon regeneration, but also forms molecular brakes that actively controls maturation of PV cells and synapse plasticity in which sulfation patterns of CS chains play a key role. Structural remodeling of the brain ECM modulates neural function during development and pathogenesis. Genetic or enzymatic manipulation of the brain ECM may restore neural plasticity and enhance recovery from nerve injury. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa. •The extracellular matrix (ECM) of the brain plays key roles in neural plasticity.•The brain ECM is rich in chondroitin sulfate and hyaluronan.•Several factors influence formation and remodeling of the brain ECM.•Perineuronal nets modulate maturation of parvalbumin-expressing inhibitory neurons.•Perisynaptic ECM controls synapse formation and dendritic spine dynamics.