Distribution and phenotype of TrkB oligodendrocyte lineage cells in the adult rat spinal cord

Abstract

The distribution and phenotype of a previously undescribed population of nonneuronal cells in the intact spinal cord that expresses TrkB, the cognate receptor for brain derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4), were characterized by examining the extent of co-localization of TrkB with NG2, which identifies oligodendrocyte progenitors (OPCs) or CC1, a marker for mature oligodendrocytes (OLs). All TrkB nonneuronal cells expressed Olig2, confirming their role in the OL lineage. Similar to OPCs and OLs, TrkB cells resided in gray and white matter of the spinal cord in similar abundance. Less than 2% of TrkB cells expressed NG2, while over 80% of TrkB cells in the adult spinal cord co-expressed CC1. Most OPCs did not express detectable levels of TrkB, however a small OPC pool (~5%) showed TrkB immunoreactivity. The majority of mature OLs (~65%) expressed TrkB, but a population of mature OLs (~36%) did not express TrkB at detectable levels, and 17% of TrkB nonneuronal cells did not express NG2 or CC1. Approximately 20% of the TrkB nonneuronal population in the ventral horn resided in close proximity to motor neurons and were categorized as perineuronal. We conclude that TrkB is expressed by several pools of OL lineage cells in the adult spinal cord. These findings are important in understanding the neurotrophin regulation of OL lineage cells in the adult spinal cord.

Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology

“…In the rat spinal cord, over 80% TrkB-expressing cells co-express CC1, indicating differentiated OLs. A small OPC pool also show TrkB immunoreactivity, suggesting a function in growth (Coulibaly et al, 2014). Ablation of the TrkB receptor in the oligodendroglial lineage disrupts myelination, and indirectly increases the density of OPCs (Wong et al, 2013).…”

Increased Cx32 expression in spinal cord TrkB oligodendrocytes following peripheral axon injury

“…These TrkB expressing cells, which are increased in number by the peripheral axon injury, may represent a population of OL lineage cells that has upregulated TrkB expression while ‘in transition’ from a progenitor to a mature OL state. We are confident that the TrkB cells are of the OL cell lineage since all non-neuronal cells expressing full length TrkB were shown to also express Olig2 (18), and astrocytes express only the truncated isoform of TrkB (23, 24). …”

“…In an effort to determine which cell type in the OL lineage was responsible for the increased number of plaques per cell, double labeling of Cx32 with the OL markers TrkB [17,18], CC1 [19], or NG2 [20] was carried out. In a recent study from our lab, the majority of TrkB cells (>80%) were shown to colocalize CC1, indicating their mature phenotype [18], yet a proportion of TrkB cells may represent a separate pool of OL linage cells [18] and thus TrkB cells were considered separately.…”

“…In a recent study from our lab, the majority of TrkB cells (>80%) were shown to colocalize CC1, indicating their mature phenotype [18], yet a proportion of TrkB cells may represent a separate pool of OL linage cells [18] and thus TrkB cells were considered separately. Cx32 immunofluorescent plaques that associated with TrkB as well as CC1 cells were observed predominantly around the cell body (Figs.…”

“…Further, we have shown that the majority (86%) of the TrkB cells responding to the injury are mature OLs and typically express CC1 [18], but that a pool of TrkB cells does not express either NG2 or CC1. These TrkB expressing cells, which are increased in number by the peripheral axon injury, may represent a population of OL lineage cells that has upregulated TrkB expression while ‘in transition’ from a progenitor to a mature OL state.…”