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000276278 1001_ $$0P:(DE-2719)9001469$$aBaidoe-Ansah, David$$b0$$eFirst author$$udzne
000276278 245__ $$aNeurocan regulates axon initial segment organization and neuronal activity.
000276278 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2025
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000276278 520__ $$aThe 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.
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000276278 650_7 $$2Other$$aExtracellular matrix
000276278 650_7 $$2Other$$aneurocan
000276278 650_7 $$2Other$$aneuronal excitability
000276278 650_7 $$2Other$$aperineuronal net
000276278 650_7 $$2Other$$asynaptic plasticity
000276278 7001_ $$0P:(DE-2719)2814120$$aMirzapourdelavar, Hadi$$b1$$udzne
000276278 7001_ $$0P:(DE-2719)9001621$$aAleshin, Stepan$$b2$$udzne
000276278 7001_ $$0P:(DE-2719)2814326$$aSchott, Björn Hendrik$$b3$$udzne
000276278 7001_ $$aSeidenbecher, Constanze$$b4
000276278 7001_ $$aKaushik, Rahul$$b5
000276278 7001_ $$0P:(DE-2719)2810577$$aDityatev, Alexander$$b6$$eLast author$$udzne
000276278 773__ $$0PERI:(DE-600)2005263-7$$a10.1016/j.matbio.2025.01.001$$gVol. 136, p. 22 - 35$$p22 - 35$$tMatrix biology$$v136$$x0945-053X$$y2025
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