The age- and amyloid-β-related increases in Nogo B contribute to microglial activation

• Published in: Neurochemistry international 2011-02, Vol.58 (2), p.161-168
• Main Authors: Murphy, Kevin J., Miller, Anne-Marie, Thelma, R., Cowley, F., Fionnuala Cox, F., Lynch, Marina A.
• Format: Article
• Language: English
• Subjects: Age; Aging - metabolism; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - toxicity; Amyloid-β; Animals; Biological and medical sciences; Caspase; Cells, Cultured; Coculture Techniques; Fundamental and applied biological sciences. Psychology; Gliosis - metabolism; Gliosis - pathology; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Inflammation - metabolism; Inflammation - pathology; Long term potentiation; Male; Microglia - drug effects; Microglia - metabolism; Microglial activation; Myelin Proteins - biosynthesis; Myelin Proteins - metabolism; Neuroinflammation; Nogo; Nogo Proteins; Rats; Rats, Wistar; Synaptic deterioration; Up-Regulation - drug effects; Up-Regulation - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2010.11.009

▶ In this study, we investigated the effect of Nogo B in brain. ▶ Its expression is increased in hippocampus of aged and Abeta-treated rats. ▶ This is accompanied by microglial activation, caspase 3 activation and decreased LTP. ▶ In vitro, Nogo B increases neuronal caspase 3 activity and microglial activation. ▶ We conclude that Nogo B exerts inflammatory and neurodegenerative effects. The family of reticulons include three isoforms of the Nogo protein, Nogo A, Nogo B and Nogo C. Nogo A is expressed on neuronal tissue and its primary effect is widely acknowledged to be inhibition of neurite outgrowth. Although both Nogo B and Nogo C are also expressed in neuronal tissue, their roles in the CNS remain to be identified. In this study, we set out to assess whether expression of Nogo A or Nogo B was altered in tissue prepared from aged rats in which increased microglial activation is accompanied by decreased synaptic plasticity. The data indicate that Nogo B, but not Nogo A, was markedly increased in hippocampal tissue prepared from aged rats and that, at least in vitro, Nogo B increased several markers of microglial activation. In a striking parallel with the age-related changes, we demonstrate that intracerebroventricular delivery of amyloid-β (Aβ) 1-40 + Aβ 1-42 for 8 days was associated with a depression of long-term potentiation (LTP) and an increase in markers of microglial activation and Nogo B. In both models, evidence of cell stress was identified by increased activity of caspases 8 and 3 and importantly, incubation of cultured neurons in the presence of Nogo B increased activity of both enzymes. The data identify, for the first time, an effect of Nogo B in the brain and specifically show that its expression is increased in conditions where synaptic plasticity is compromised.