Nerve growth factor and neurotrophin-3 differentially regulate the proliferation and survival of developing rat brain oligodendrocytes. 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 Ivacaftor hydrate cord. (VonDran et al., 2010; VonDran et al., 2011) and (McTigue et al., 1998). Yet our analysis revealed that only a relatively small proportion of OPCs in the adult spinal cord expressed TrkB at detectable levels. Horner and colleagues (2002) reported that ~3% of the NG2 population in the spinal cord was in the cell cycle over a 12 day period, while 97% of the cells were quiescent or carrying out other activities. These numbers compare favorably with the small proportion of NG2+/TrkB+ cells observed in our study. Because BDNF appears to regulate OPC proliferation and differentiation, we propose that the OPCs showing detectable levels of TrkB in the present study may represent the pool that has committed to either self-renew or to differentiate into OLs (Barnabe-Heider et al., 2008). Rather than exist in a quiescent state, cells in this stage would be actively dividing and/or maturing into OLs similar to the model proposed by Baumann and Pham-Dinh Ivacaftor hydrate (2001). It should be noted that at least some of the OPCs that were not expressing detectable levels of TrkB may have been involved in functions other than renewal or OL differentiation and/or Ivacaftor hydrate might be regulated by other stimulatory molecules, such as glutamate, FGF, PDGF, NGF and/or other neurotrophins (Miller, 2002; Nishiyama et al., 2009). Regardless of their exact function, our data support the existence of a heterogeneous NG2 cell population in the adult spinal cord GM and Lum WM. Our results are supported by previous findings that the population of NG2 cells is heterogeneous in the adult spinal cord (Horner et al., 2002). As expected, a majority of the CC1 cells co-expressed TrkB, suggesting that a large proportion of mature OLs are regulated by BDNF and/or NT-4. Yet a significant subset (~36%) of mature OLs either expressed TrkB at very low levels or did not express TrkB. It is possible that a subset of the mature OL subpopulation within the spinal cord loses responsivity to, or possibly is not regulated by, BDNF or NT4. When considering the phenotype of the TrkB population in the spinal cord, 81% of the TrkB cells expressed the mature OL marker, CC1, while less than 2% of TrkB cells expressed the OPC marker NG2. Therefore approximately 17% of the TrkB Ivacaftor hydrate cells did not express detectable levels of NG2 or CC1. Our studies as well as others show no localization of TrkB in other nonneuronal cells such as astrocytes or microglia (Skup et al., 2002; Garraway et al., 2011) and these TrkB only are not in the size range of neurons. While it is possible that these cells expressed NG2 or CC1 below the level of detection of our antibodies, they also may represent a subpopulation of TrkB cells in transition from the precursor (NG2+/TrkB+) to the mature stage (CC1+/TrkB+). Indeed, the presence Ivacaftor hydrate of an immature OL stage, one that occurs between the precursor and mature stages, in which NG2 is down-regulated, but detectable levels of CC1 are not evident, has been suggested (Baumann and Pham-Dinh, 2001; Miller, 2002; Nishiyama et al., 2009). 3.2. Distribution of OL lineage cells in the adult spinal cord OLs typically are known for their role in myelination and thus would be expected to be most prevalent in the white matter. However the results of the present study suggest that.