Abstract
BackgroundPerineuronal nets (PNNs), which are localized around neurons during development, are specialized forms of neural extracellular matrix with neuroprotective and plasticity-regulating roles. Hyaluronan and proteoglycan link protein 1 (HAPLN1), tenascin-R (TNR) and aggrecan (ACAN) are key elements of PNNs. In diseases characterized by neuritogenesis defects, the expression of these proteins is known to be downregulated, suggesting that PNNs may have a role in neural differentiation.MethodsIn this study, the mRNA and protein levels of HAPLN1, TNR and ACAN were determined and compared at specific time points of neural differentiation. We used PC12 cells as the in vitro model because they reflect this developmental process.ResultsOn day 7, the HAPLN1 mRNA level showed a 2.9-fold increase compared to the non-differentiated state. However, the cellular HAPLN1 protein level showed a decrease, indicating that the protein may have roles in neural differentiation, and may be secreted during the early period of differentiation. By contrast, TNR mRNA and protein levels remained unchanged, and the amount of cellular ACAN protein showed a 3.7-fold increase at day 7. These results suggest that ACAN may be secreted after day 7, possibly due to its large amount of post-translational modifications.ConclusionsOur results provide preliminary data on the expression of PNN elements during neural differentiation. Further investigations will be performed on the role of these elements in neurological disease models.
Highlights
Perineuronal nets (PNNs), which are localized around neurons during development, are specialized forms of neural extracellular matrix with neuroprotective and plasticity-regulating roles
We aimed to discover whether PNNs are associated with neural differentiation by determining the changes in the mRNA and protein levels of Hyaluronan and proteoglycan link protein 1 (HAPLN1), TNR and ACAN throughout the neural differentiation process
On days 5 and 7, 1.7-fold (p < 0.05) and 2.9-fold (p < 0.0001) increases in HAPLN1 mRNA levels were respectively observed compared to the non-differentiated state (Fig. 2a)
Summary
Perineuronal nets (PNNs), which are localized around neurons during development, are specialized forms of neural extracellular matrix with neuroprotective and plasticity-regulating roles. Perineuronal nets (PNNs) are specialized substructures of the neural extracellular matrix (ECM), which surround cell soma and proximal neurites of neurons in the hippocampus, cerebellum, brain stem and spinal cord [1, 2]. CSPGs interact with HA polymer chains on the cell surface This interaction is stabilized by link proteins that bind both HA and CSPGs. On the other surface, the Cterminus of the CSPG core protein directly interacts with trimeric TNR, creating the highly organized PNN structure [8, 9]
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