Abstract

Reelin is a large extracellular matrix (ECM) glycoprotein secreted by several neuronal populations in a specific manner in both the developing and the adult central nervous system. The extent of Reelin protein distribution and its functional role in the adult neocortex is well documented in different mammal models. However, its role in the adult spinal cord has not been well characterized and its distribution in the rodent spinal cord is fragmentary and has not been investigated in carnivores or primates as of yet. To gain insight into which neuronal populations and specific circuits may be influenced by Reelin in the adult spinal cord, we have conducted light and confocal microscopy study analysis of Reelin-immunoreactive cell types in the adult spinal cord. Here, we describe and compare Reelin immunoreactive cell type and distribution in the spinal cord of adult non-human primate (macaque monkeys, Macaca mulatta), carnivore (ferret, Mustela putorius) and rodent (rat, Rattus norvegicus). Our results show that in all three species studied, Reelin-immunoreactive neurons are present in the intermediate gray matter, ventricular zone and superficial dorsal horn and intermedio-lateral nucleus, while positive cells in the Clarke nucleus are only found in rats and primates. In addition, Reelin intermediolateral neurons colocalize with choline acetyltransferase (ChAT) only in macaque whilst motor neurons also colocalize Reelin and ChAT in macaque, ferret and rat spinal cord. The different expression patterns might reflect a differential role for Reelin in the pathways involved in the coordination of locomotor activity in the fore- and hind limbs.

Highlights

  • Reelin is a large extracellular matrix (ECM) molecule that is crucial for the neuronal migrations involving the laminar organization of different brain regions and sympathetic preganglionic neurons during development (Tissir and Goffinet, 2003; Jossin, 2004; Niu et al, 2004; Yip et al, 2007; Krüger et al, 2010)

  • Reelin immunoreactive cells are found in the lateral spinal nucleus (LSN) in rats (Figure 1C)

  • Reelin immunoreactivity is present in the preganglionic neurons of the intermediate lateral nucleus (ILN) in a non-human primate, ferret and rat and immunolocalize with choline acetyltransferase (ChAT) in the non-human primates (Figures 3A–L, 4D–F)

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Summary

Introduction

Reelin is a large extracellular matrix (ECM) molecule that is crucial for the neuronal migrations involving the laminar organization of different brain regions and sympathetic preganglionic neurons during development (Tissir and Goffinet, 2003; Jossin, 2004; Niu et al, 2004; Yip et al, 2007; Krüger et al, 2010). Other studies have suggested an involvement of Reelin signaling in pain processing in the spinal cord (Villeda et al, 2006; Akopians et al, 2008; Wang et al, 2012). The distribution of cells expressing Reelin in the adult spinal cord has been examined fragmentarily, and only in rodents (Phelps et al, 1991; Kubasak et al, 2004; Villeda et al, 2006). Our results suggest that Reelin is involved and conserved in adult nociceptive pathways across phylogenetically separate mammalian species. Some neurons in proprioceptive and motor spinal pathways express detectable levels of Reelin in some species, but not in others

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