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@ARTICLE{BaidoeAnsah:276278,
author = {Baidoe-Ansah, David and Mirzapourdelavar, Hadi and Aleshin,
Stepan and Schott, Björn Hendrik and Seidenbecher,
Constanze and Kaushik, Rahul and Dityatev, Alexander},
title = {{N}eurocan regulates axon initial segment organization and
neuronal activity.},
journal = {Matrix biology},
volume = {136},
issn = {0945-053X},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DZNE-2025-00257},
pages = {22 - 35},
year = {2025},
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 regulation 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.},
keywords = {Animals / Mice / Axon Initial Segment: metabolism /
Neurocan: metabolism / Neurocan: genetics / Mice, Knockout /
NAV1.6 Voltage-Gated Sodium Channel: metabolism / NAV1.6
Voltage-Gated Sodium Channel: genetics / Ankyrins:
metabolism / Ankyrins: genetics / Neurons: metabolism /
Proto-Oncogene Proteins c-fos: genetics / Proto-Oncogene
Proteins c-fos: metabolism / Aggrecans: metabolism /
Aggrecans: genetics / Cells, Cultured / Extracellular
Matrix: metabolism / Axons: metabolism / Gene Expression
Regulation / Extracellular matrix (Other) / neurocan (Other)
/ neuronal excitability (Other) / perineuronal net (Other) /
synaptic plasticity (Other)},
cin = {AG Dityatev / AG Fischer},
ddc = {570},
cid = {I:(DE-2719)1310007 / I:(DE-2719)1410002},
pnm = {351 - Brain Function (POF4-351) / 352 - Disease Mechanisms
(POF4-352)},
pid = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39788215},
doi = {10.1016/j.matbio.2025.01.001},
url = {https://pub.dzne.de/record/276278},
}