Journal Article

DZNE-2025-00257

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neurocan regulates axon initial segment organization and neuronal activity.

Baidoe-Ansah, D. (First author)DZNE* ; Mirzapourdelavar, H.DZNE* ; Aleshin, S.DZNE* ; Schott, B. H.DZNE* ; Seidenbecher, C. ; Kaushik, R. ; Dityatev, A. (Last author)DZNE*

2025
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.matbio.2025.01.001

Abstract: The neural extracellular matrix (ECM) accumulates in the form of perineuronal nets (PNNs), particularly around fast-spiking GABAergic interneurons in the cortex and hippocampus, but also around synapses and in association with the axon initial segments (AIS) and nodes of Ranvier. Increasing evidence highlights the role of Neurocan (Ncan), a brain-specific component of ECM, in the pathophysiology of neuropsychiatric disorders like bipolar disorder and schizophrenia. Ncan localizes at PNNs, perisynaptically, and at the nodes of Ranvier and the AIS, highlighting its potential role in regulating axonal excitability. Here, we used knockdown and knockout approaches in mouse primary cortical neurons in combination with immunocytochemistry, western blotting and electrophysiological techniques to characterize the role of Ncan in the organization of PNNs and AISs and the upregulation of neuronal activity. We found that reduced Ncan levels led to remodeling of PNNs around neurons via upregulation of Aggrecan mRNA and protein levels, increased expression of activity-dependent c-Fos and FosB genes and elevated spontaneous synaptic activity. The latter correlated with increased levels of Ankyrin-G in the AIS, particularly in excitatory neurons, and with the elevated expression of Nav1.6 channels. Our results suggest that Ncan regulates the expression of key proteins in PNNs and AISs and provide new insights into its role in fine-tuning neuronal functions.

Keyword(s): Extracellular matrix ; neurocan ; neuronal excitability ; perineuronal net ; synaptic plasticity

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Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)
2. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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