Expression of Nogo-A Is Decreased with Increasing Gestational Age in the Human Fetal Brain

Abstract

Nogo is a member of the reticulon family. Our understanding of the physiological functions of the Nogo-A protein has grown over the last few years, and this molecule is now recognized as one of the most important axonal regrowth inhibitors present in central nervous system (CNS) myelin. Nogo-A plays other important roles in nervous system development, epilepsy, vascular physiology, muscle pathology, stroke, inflammation, and CNS tumors. Since the exact role of Nogo-A protein in human brain development is still poorly understood, we studied its cellular and regional distribution by immunohistochemistry in the frontal lobe of 30 human fetal brains. Nogo-A was expressed in the following cortical zones: ependyma, ventricular zone, subventricular zone, intermediate zone, subplate, cortical plate, and marginal zone. The number of positive cells decreased significantly with increasing gestational age in the subplate and marginal zone. Using different antibodies, changes in isoform expression and dimerization states could be shown between various cortical zones. The results demonstrate a significant change in the expression of Nogo-A during the development of the human brain. The effects of its time- and region-specific regulation have to be further studied in detail.

A Nogo-Like Signaling Perspective from Birth to Adulthood and in Old Age: Brain Expression Patterns of Ligands, Receptors and Modulators

“…Our findings confirm and expand existing knowledge (Habib et al, 1998 ; Josephson et al, 2001 , 2002 ; Vourc'h et al, 2003 ; Okafuji and Tanaka, 2005 ; Venkatesh et al, 2005 ; Barrette et al, 2007 ; Funahashi et al, 2008 ; Haybaeck et al, 2012 ; VanGuilder Starkey et al, 2013 ) regarding the expression of genes involved in Nogo-like signaling during postnatal development, in the adult and the aged mouse brain. Together, these findings reveal gene- area- and age-specific roles of these genes, and suggests stronger roles for Nogo-like signaling in areas in which structural synaptic plasticity is important.…”

“…So far, the Nogo-system has been investigated mostly with a focus on individual or smaller groups of components (Habib et al, 1998 ; Huber et al, 2002 ; Josephson et al, 2002 ; Tozaki et al, 2002 ; Richard et al, 2005 ; Barrette et al, 2007 ; Haybaeck et al, 2012 ; Kumari and Thakur, 2014 ). The expression has also been investigated in response to activation and/or injury (Josephson et al, 2003 ; Mingorance et al, 2004 ; Cafferty et al, 2010 ; Borrie et al, 2012 ).…”

Non-clinical development of ozanezumab: a humanised antibody targeting the amino terminus of neurite outgrowth inhibitor A (Nogo-A)

“…4,8,9 Nogo-A is the longest of several splice forms of the Nogo/reticulon (RTN)-4 gene 10 and protein expression is enriched in the brain and spinal cord of rats 11 and humans; 12 for review see Schwab. 15 Although the exact role of Nogo-A protein in development is not well understood, there is evidence to suggest that Nogo-A is associated with the regulation of neuronal synapse morphology and architecture, 16,17 possibly via cytoskeletal reorganization, 18 with emerging roles for Nogo-A in the stabilisation of neuronal networks, either developmentally 16 19 Indeed, Nogo-A may represent an important regulator of neuronal plasticity associated with learning 20 and Nogo-A down regulation is associated with altered synaptic plasticity during aging and may play a role in age-related cognitive decline. 15 Although the exact role of Nogo-A protein in development is not well understood, there is evidence to suggest that Nogo-A is associated with the regulation of neuronal synapse morphology and architecture, 16,17 possibly via cytoskeletal reorganization, 18 with emerging roles for Nogo-A in the stabilisation of neuronal networks, either developmentally 16 19 Indeed, Nogo-A may represent an important regulator of neuronal plasticity associated with learning 20 and Nogo-A down regulation is associated with altered synaptic plasticity during aging and may play a role in age-related cognitive decline.…”

“…9 Neuronal Nogo-A plays a role in central nervous system development and plasticity (see reviews 13,14 ) and significant time-and region-specific changes in Nogo-A expression are observed during the development of the human brain. 15 Although the exact role of Nogo-A protein in development is not well understood, there is evidence to suggest that Nogo-A is associated with the regulation of neuronal synapse morphology and architecture, 16,17 possibly via cytoskeletal reorganization, 18 with emerging roles for Nogo-A in the stabilisation of neuronal networks, either developmentally 16 or during the processes of memory consolidation in the mature nervous system. 19 Indeed, Nogo-A may represent an important regulator of neuronal plasticity associated with learning 20 and Nogo-A down regulation is associated with altered synaptic plasticity during aging and may play a role in age-related cognitive decline.…”

Multiple Sclerosis

“…Although Nogo-A-dependent signaling has been primarily defined in the context of CNS injury, it may also play a fundamental neurobiological role in development. In the human embryo, it has been shown that Nogo-A expression was decreased in brain on maturation (Haybaeck and others 2012). Furthermore, it was reported that in human embryonic spinal cords Nogo-A can be localized to axons, whereas NgR expression was up-regulated in mouse spinal cord when axons crossing occurred in the floor plate.…”