Abstract
The locus coeruleus (LC) nucleus modulates adaptive behavioral responses to stress and dysregulation of LC neuronal activity is implicated in stress-induced mental illnesses. The LC is composed primarily of noradrenergic neurons together with various glial populations. A neuroglia cell-type largely unexplored within the LC is the NG2 cell. NG2 cells serve primarily as oligodendrocyte precursor cells throughout the brain. However, some NG2 cells are in synaptic contact with neurons suggesting a role in information processing. The aim of this study was to neurochemically and anatomically characterize NG2 cells within the rat LC. Furthermore, since NG2 cells have been shown to proliferate in response to traumatic brain injury, we investigated whether such NG2 cells plasticity also occurs in response to emotive insults such as stress. Immunohistochemistry and confocal microscopy revealed that NG2 cells were enriched within the pontine region occupied by the LC. Close inspection revealed that a sub-population of NG2 cells were located within unique indentations of LC noradrenergic somata and were immunoreactive for the neuronal marker NeuN whilst NG2 cell processes formed close appositions with clusters immunoreactive for the inhibitory synaptic marker proteins gephyrin and the GABA-A receptor alpha3-subunit, on noradrenergic dendrites. In addition, LC NG2 cell processes were decorated with vesicular glutamate transporter 2 immunoreactive puncta. Finally, 10 days of repeated restraint stress significantly increased the density of NG2 cells within the LC. The study demonstrates that NG2 IR cells are integral components of the LC cellular network and they exhibit plasticity as a result of emotive challenges.
Highlights
The brainstem locus coeruleus (LC)-noradrenergic system (Berridge and Waterhouse, 2003) is an integral orchestrator of the cognitive loop of the stress response which ensures optimal decision making in the face of adversity (Valentino and Van Bockstaele, 2008)
In the current study, we investigated the expression of NG2expressing cells within the LC with a view to determining the anatomical relationships between such neuroglia cells and the principal noradrenergic neurons of this nucleus during development and following exposure to repeated stress
A further population of Nerve/glial antigen 2 (NG2) immunopositive cells which were not located in somatic indentations were randomly scattered throughout the extent of the LC with their processes located in close apposition to either tyrosine hydroxylase (TH) immunopositive profiles or profiles immunopositive for glial fibrillary acidic protein (GFAP), a marker of astrocytes (Figure 1C)
Summary
The brainstem locus coeruleus (LC)-noradrenergic system (Berridge and Waterhouse, 2003) is an integral orchestrator of the cognitive loop of the stress response which ensures optimal decision making in the face of adversity (Valentino and Van Bockstaele, 2008) This LC-noradrenergic stress response is generally an adaptive mechanism which allows the individual to contend with daily challenges and is essential for survival. A central molecule in the LC-noradrenergic stress pathways is the stress related hormone, corticotrophin releasing hormone (CRH; Valentino et al, 1992, 1993, 1998) which directly activates LC noradrenergic neurons (Valentino et al, 1983; Jedema and Grace, 2004; Swinny et al, 2010) It is currently unclear whether other cell-types within the LC nucleus, apart from the principal noradrenergic neurons, are responsive to stressors. A neuroglia cell that is unexplored within the LC is the NG2 cell (Butt et al, 2002)
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