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Updated: Jun 3, 2025
06:53
Use of Primary Cultured Hippocampal Neurons to Study the Assembly of Axon Initial Segments
Published on: February 12, 2021
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Neurocan regulates axon initial segment organization and neuronal activity.
David Baidoe-Ansah1, Hadi Mirzapourdelavar1, Stepan Aleshin1
1German Center for Neurodegenerative Diseases (DZNE), Helmholtz Association of German Research Centers, Magdeburg, Germany.
Summary
Neurocan (Ncan), an extracellular matrix protein, influences brain cell connections and activity. Reduced Ncan alters perineuronal nets and axon initial segments, impacting neuronal function and potentially contributing to neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- The neural extracellular matrix (ECM) forms perineuronal nets (PNNs) around neurons, influencing neuronal function.
- Neurocan (Ncan) is a brain-specific ECM component implicated in neuropsychiatric disorders.
- Ncan's localization suggests a role in regulating axonal excitability and neuronal activity.
Purpose of the Study:
- To investigate the role of Neurocan (Ncan) in the structural organization of PNNs and axon initial segments (AIS).
- To determine how Ncan affects neuronal activity and gene expression in primary cortical neurons.
- To elucidate Ncan's contribution to the pathophysiology of neuropsychiatric conditions.
Main Methods:
- Utilized knockdown and knockout mouse models of primary cortical neurons.
- Employed immunocytochemistry, Western blotting, and electrophysiological techniques.
- Analyzed PNN and AIS structure, gene expression (aggrecan, c-Fos, FosB), and synaptic activity.
Main Results:
- Reduced Ncan levels caused PNN remodeling, evidenced by aggrecan upregulation.
- Ncan reduction led to increased expression of activity-dependent genes (c-Fos, FosB).
- Observed elevated spontaneous synaptic activity, increased ankyrin-G, and Nav1.6 channel expression in AIS.
Conclusions:
- Ncan plays a crucial role in organizing PNNs and AIS structures.
- Ncan influences neuronal excitability and synaptic activity.
- Findings provide insights into Ncan's function in fine-tuning neural network activity and its relevance to neuropsychiatric disorders.
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