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In the search for molecules that may alter the formation of amyloid-β (Aβ) protofibrils, it has been shown that the Nogo-system can interact and bind to amyloid-β protein precursor and thus affect the amount of Aβ that is formed and deposited in the brain. To further address this issue in vivo, we crossed mice that overexpress Nogo receptor 1 (NgR1), 'MemoFlex', in forebrain neurons, with plaque forming APPswe/PSEN1(ΔE9) mice, to investigate if increased levels of NgR1 would influence plaque load or cognitive function in the resulting MemoFlex/APPswe/PSEN1(ΔE9) transgenic mice. We used a radial arm water maze and the Morris water maze to measure cognitive function. We did not find any significant effect of NgR1 overexpression on the performance of APPswe/PSEN1(ΔE9) mice in the radial arm water maze test. However, MemoFlex/APPswe/PSEN1(ΔE9) mice were found to be significantly impaired in the Morris water maze. We also analyzed the amount of plaques in the two mouse models without finding any significant difference in plaque load in the cerebral cortex or the hippocampal formation. It therefore appears that overexpression of NgR1 in APPswe/PSEN1(ΔE9) mice does not have any marked effects on Aβ levels, yet appears to impair spatial cognitive abilities. We conclude that strong overexpression of NgR1 in forebrain neurons impairs aspects of cognitive function but does not markedly alter plaque load in plaque-forming APPswe/PSEN1(ΔE9) mice. Thus high levels of membrane-bound NgR1 present since early postnatal life does not influence the development of plaques in mice carrying the two human plaque-causing mutations APPswe and PSEN1(ΔE9). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.