Neurofascin: A switch between neuronal plasticity and stability

Kriebel, Martin; Wuchter, Jennifer; Trinks, Sabine; Volkmer, Hansjürgen

doi:10.1016/j.biocel.2012.01.012

Cited by 70 publications

(71 citation statements)

References 33 publications

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“…In this study, we aimed to validate a PRM-MS assay consisting of a panel of proteins presumed to be involved in processes regarding secretory vesicle functioning, synaptic functioning, and innate immunity [12][13][14][15][16][17][18][19][20][21]. Having performed a pilot study [29], in the present study, we investigated this panel in a larger and independent cohort that included subjects with MCI in addition to patients with AD dementia and control subjects.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, a decreased level in brain tissue and CSF of patients with AD compared with control subjects has also been described [27,28,40]. Studies on the role of NRXNs, NPTX1, NFASC, and NCANP in AD are rare, although the proteins have all been suggested to have a role in synapse formation, plasticity, and stability [17][18][19][20][21]. On the basis of using MS-based proteomics, CSF NRXN-1 has been found to be slightly decreased in patients with AD compared with control subjects in a small cohort of 16 subjects [36].…”

Section: Discussionmentioning

confidence: 99%

“…The PRM panel consisted of neurosecretory protein VGF (VGF), chromogranin A (CHGA), and secretogranin 2 (SCG2), granins that are presumed to be involved in axonal or synaptic vesicle transport (the granins VGF, CHGA, and SCG2) [12]; cystatin C (CysC), a protease involved in Aβ degradation [13,14]; β 2 -microglobulin (β 2 M) and lysozyme C (LysC), proteins involved in the innate immune system [15,16]; and neurexins (NRXNs) NRXN-1, NRXN-2, and NRXN-3 as well as neuronal pentraxin 1 (NPTX1), neurofascin (NFASC), and neurocan core protein (NCANP), proteins involved in synapse formation and stabilization [17][18][19][20][21]. Several of these proteins, including VGF, CHGA, SCG2, CysC, and β 2 M, have been suggested in previous studies to be involved in AD pathology [12][13][14][22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

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Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer’s disease

et al. 2018

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Background: We investigated whether a panel of 12 potential novel biomarkers consisting of proteins involved in synapse functioning and immunity would be able to distinguish patients with Alzheimer's disease (AD) and patients with mild cognitive impairment (MCI) from control subjects. Methods: We included 40 control subjects, 40 subjects with MCI, and 40 subjects with AD from the Amsterdam Dementia Cohort who were matched for age and sex (age 65 ± 5 years, 19 [48%] women). The mean follow-up of patients with MCI was 3 years. Two or three tryptic peptides per protein were analyzed in cerebrospinal fluid using parallel reaction monitoring mass spectrometry. Corresponding stable isotope-labeled peptides were added and used as reference peptides. Multilevel generalized estimating equations (GEEs) with peptides clustered per subject and per protein (as within-subject variables) were used to assess differences between diagnostic groups. To assess differential effects of individual proteins, we included the diagnosis × protein interaction in the model. Separate GEE analyses were performed to assess differences between stable patients and patients with progressive MCI (MCI-AD).Results: There was a main effect for diagnosis (p < 0.01) and an interaction between diagnosis and protein (p < 0.01). Analysis stratified according to protein showed higher levels in patients with MCI for most proteins, especially in patients with MCI-AD. Chromogranin A, secretogranin II, neurexin 3, and neuropentraxin 1 showed the largest effect sizes; β values ranged from 0.53 to 0.78 for patients with MCI versus control subjects or patients with AD, and from 0.67 to 0.98 for patients with MCI-AD versus patients with stable MCI. In contrast, neurosecretory protein VGF was lower in patients with AD than in patients with MCI (ß = −0.93 [SE 0.22]) and control subjects (ß = 0.46 [SE 0.19]). Conclusions: Our results suggest that several proteins involved in vesicular transport and synaptic stability are elevated in patients with MCI, especially in patients with MCI progressing to AD dementia. This may reflect early events in the AD pathophysiological cascade. These proteins may be valuable as disease stage or prognostic markers in an early symptomatic stage of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer’s disease

et al. 2018

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“…Neurofascin is expressed in multiple isoforms that are spatially and temporally regulated (for a comprehensive review see [15]). Neurofascin expression was shown to be required for the stabilization of GABAergic input at the AIS of dentate gyrus granular cells of adult rats which express NF186 [8].…”

Section: Knockdown Of Neurofascin In Juvenile Ratsmentioning

confidence: 99%

Dentate Gyrus Local Circuit is Implicated in Learning Under Stress—a Role for Neurofascin

et al. 2014

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The inhibitory synapses at the axon initial segment (AIS) of dentate gyrus granular cells are almost exclusively innervated by the axo-axonic chandelier interneurons. However, the role of chandelier neurons in local circuitry is poorly understood and controversially discussed. The cell adhesion molecule neurofascin is specifically expressed at the AIS. It is crucially required for the stabilization of axo-axonic synapses. Knockdown of neurofascin is therefore a convenient tool to interfere with chandelier input at the AIS of granular neurons of the dentate gyrus. In the current study, feedback and feedforward inhibition of granule cells was measured in the dentate gyrus after knockdown of neurofascin and concomitant reduction of axo-axonic input. Results show increased feedback inhibition as a result of neurofascin knockdown, while feedforward inhibition remained unaffected. This suggests that chandelier neurons are predominantly involved in feedback inhibition. Neurofascin knockdown rats also exhibited impaired learning under stress in the two-way shuttle avoidance task. Remarkably, this learning impairment was not accompanied by differences in electrophysiological measurements of dentate gyrus LTP. This indicates that the local circuit may be involved in (certain types) of learning.

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“…CNTNAP2 is a well-known FOXP2 target (Vernes et al, 2008) and a candidate for language delay and language impairment (Petrin et al, 2010; Sehested et al, 2010), intellectual disability (Gregor et al, 2011), and autism (Alarcón et al, 2008; Bakkaloglu et al, 2008), The AMH CNTNAP2 exhibits a fixed change (Ile345Val) compared to the Denisovan protein (Meyer et al, 2012). Moreover, CNTNAP2 is related to NFASC, a protein involved in neurite outgrowth and the formation of postsynaptic components (Kriebel et al, 2012) that shows a fixed change (T987A) in AMHs compared to Neanderthals/Denisovans (Pääbo, 2014b, Table S1).…”

Section: Runx2 and Brain-related Genes Selected In Amhsmentioning

confidence: 99%

Possible functional links among brain- and skull-related genes selected in modern humans

Benítez‐Burraco

Boeckx

2015

Front. Psychol.

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The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language.

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Neurofascin: A switch between neuronal plasticity and stability

Cited by 70 publications

References 33 publications

Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer’s disease

Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer’s disease

Dentate Gyrus Local Circuit is Implicated in Learning Under Stress—a Role for Neurofascin

Possible functional links among brain- and skull-related genes selected in modern humans

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