Nogo-A regulates spatial learning as well as memory formation and modulates structural plasticity in the adult mouse hippocampus

Zagrebelsky, Marta; Lonnemann, Niklas; Fricke, Steffen; Kellner, Yves; Preuß, Eike B.; Michaelsen-Preusse, Kristin; Körte, Martin

doi:10.1016/j.nlm.2016.06.022

Cited by 17 publications

(25 citation statements)

References 51 publications

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“…We hypothesized that NgR1 regulates long term memory formation and showed that overexpression of a NgR1 transgene severely impairs memory formation (Karlén et al, 2009), dendritic architecture and spine densities (Karlsson et al, 2016). This is in agreement with several other groups who have showed altered structural plasticity and memory effects by modulating Nogo signaling (Delekate et al, 2011; Wills et al, 2012; Akbik et al, 2013; Petrasek et al, 2014b; Zemmar et al, 2014; Bhagat et al, 2016; Zagrebelsky et al, 2017). …”

Section: Introductionsupporting

confidence: 92%

“…The importance of the inhibitory, plasticity-regulating Nogo-like signaling system in gray matter during development and in adulthood has been revealed by studying the effects of perturbations such as blocking, decreasing, or increasing the Nogo-NgR signaling pathway, causing increased and decreased plasticity, respectively (McGee et al, 2005; Park et al, 2006a,b; Lee et al, 2008; Karlén et al, 2009; Wills et al, 2012; Akbik et al, 2013; Tews et al, 2013; Petrasek et al, 2014a; Iobbi et al, 2016; Karlsson et al, 2016; Kellner et al, 2016; Stephany et al, 2016a,b; Zagrebelsky et al, 2017). Increased levels of Nogo-A have been reported in schizophrenia (Novak et al, 2002), multiple sclerosis (Satoh et al, 2005), temporal lobe epilepsy (Bandtlow et al, 2004) and Alzheimer’s disease (Gil et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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Spatiotemporal and Long Lasting Modulation of 11 Key Nogo Signaling Genes in Response to Strong Neuroexcitation

Karlsson

Wellfelt

Olson

2017

Front. Mol. Neurosci.

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Inhibition of nerve growth and plasticity in the CNS is to a large part mediated by Nogo-like signaling, now encompassing a plethora of ligands, receptors, co-receptors and modulators. Here we describe the distribution and levels of mRNA encoding 11 key genes involved in Nogo-like signaling (Nogo-A, Oligodendrocyte-Myelin glycoprotein (OMgp), Nogo receptor 1 (NgR1), NgR2, NgR3, Lingo-1, TNF receptor orphan Y (Troy), Olfactomedin, Lateral olfactory tract usher substance (Lotus) and membrane-type matrix metalloproteinase-3 (MT3-MPP)), as well as BDNF and GAPDH. Expression was analyzed in nine different brain areas before, and at eight time points during the first 3 days after a strong neuroexcitatory stimulation, caused by one kainic acid injection. A temporo-spatial pattern of orderly transcriptional regulations emerges that strengthens the role of Nogo-signaling mechanisms for synaptic plasticity in synchrony with transcriptional increases of BDNF mRNA. For most Nogo-type signaling genes, the largest alterations of mRNA levels occur in the dentate gyrus, with marked alterations also in the CA1 region. Changes occurred somewhat later in several areas of the cerebral cortex. The detailed spatio-temporal pattern of mRNA presence and kainic acid-induced transcriptional response is gene-specific. We reveal that several different gene alterations combine to decrease (and later increase) Nogo-like signaling, as expected to allow structural plasticity responses. Other genes are altered in the opposite direction, suggesting that the system prepares in advance in order to rapidly restore balance. However, the fact that Lingo-1 shows a seemingly opposite, plasticity inhibiting response to kainic acid (strong increase of mRNA in the dentate gyrus), may instead suggest a plasticity-enhancing intracellular function of this presumed NgR1 co-receptor.

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Section: Introductionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Spatiotemporal and Long Lasting Modulation of 11 Key Nogo Signaling Genes in Response to Strong Neuroexcitation

Karlsson

Wellfelt

Olson

2017

Front. Mol. Neurosci.

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“…Furthermore, the Morris water maze test of spatial learning also revealed Nogo-A knockout mice were able to find the hidden platform faster than wild-type animals and had better long-term memory retention. This improvement in learning performance correlated with increased dendritic spine density in CA3 apical dendrites [ 91 ].…”

Section: Myelin In the Nervous Systemmentioning

confidence: 99%

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

2018

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The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury.

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“…The central nervous system relies on a balanced level of plasticity to adequately wire and rewire neuronal connections. Nogo type signaling [38] is known as a potent negative regulator of structural synaptic plasticity in the CNS [39][40][41][42]. It consists of ligands, receptors, co-receptors and modulators with a dynamic age-and activity-related expression in cortical and subcortical regions [43,44].…”

Section: Introductionmentioning

confidence: 99%

Genetic Screening of Plasticity Regulating Nogo-Type Signaling Genes in Migraine

et al. 2019

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Migraine is the sixth most prevalent disease in the world and a substantial number of experiments have been conducted to analyze potential differences between the migraine brain and the healthy brain. Results from these investigations point to the possibility that development and aggravation of migraine may include grey matter plasticity. Nogo-type signaling is a potent plasticity regulating system in the CNS and consists of ligands, receptors, co-receptors and modulators with a dynamic age- and activity-related expression in cortical and subcortical regions. Here we investigated a potential link between migraine and five key Nogo-type signaling genes: RTN4, OMGP, MAG, RTN4R and LINGO1, by screening 15 single nucleotide polymorphisms (SNPs) within these genes. In a large Swedish migraine cohort (749 migraine patients and 4032 controls), using a logistic regression with sex as covariate, we found that there was no such association. In addition, a haplotype analysis was performed which revealed three haplotype blocks. These blocks had no significant association with migraine. However, to robustly conclude that Nogo-type genotypes signaling do not influence the prevalence of migraine, further studies are encouraged.

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Nogo-A regulates spatial learning as well as memory formation and modulates structural plasticity in the adult mouse hippocampus

Cited by 17 publications

References 51 publications

Spatiotemporal and Long Lasting Modulation of 11 Key Nogo Signaling Genes in Response to Strong Neuroexcitation

Spatiotemporal and Long Lasting Modulation of 11 Key Nogo Signaling Genes in Response to Strong Neuroexcitation

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

Genetic Screening of Plasticity Regulating Nogo-Type Signaling Genes in Migraine

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