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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 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.},
      keywords     = {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},
}