Brain-derived neurotrophic factor deficiency restricts proliferation of oligodendrocyte progenitors following cuprizone-induced demyelination.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2 (TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well understood; however, increases in numbers of OPCs are restricted in BDNF+/- mice following cuprizone-elicited demyelination. Here, we investigate whether these blunted increases in OPCs are associated with changes in proliferation.

p75NTR, but not proNGF, is upregulated following status epilepticus in mice.

ProNGF and p75(NTR) are upregulated and induce cell death following status epilepticus (SE) in rats. However, less is known about the proneurotrophin response to SE in mice, a more genetically tractable species where mechanisms can be more readily dissected. We evaluated the temporal- and cell-specific induction of the proneurotrophins and their receptors, including p75(NTR), sortilin, and sorCS2, following mild SE induced with kainic acid (KA) or severe SE induced by pilocarpine.

Astrocyte-derived BDNF supports myelin protein synthesis after cuprizone-induced demyelination.

It is well established that BDNF may enhance oligodendrocyte differentiation following a demyelinating lesion, however, the endogenous sources of BDNF that may be harnessed to reverse deficits associated with such lesions are poorly defined. Here, we investigate roles of astrocytes in synthesizing and releasing BDNF. These cells are known to express BDNF following injury in vivo.

Levels of BDNF impact oligodendrocyte lineage cells following a cuprizone lesion.

Previous work in culture has shown that basal forebrain (BF) oligodendrocyte (OLG) lineage cells respond to BDNF by increasing DNA synthesis and differentiation. Further, in the BF in vivo, reduced levels of BDNF as seen in BDNF(+/-) mice result in reduced numbers of NG2+ cells and deficits in myelin proteins throughout development and in the adult, suggesting that BDNF impacts the proliferating population of OLGs as well as differentiation in vivo. In this study, to investigate the roles BDNF may play in the repair of a demyelinating lesion, the cuprizone model was used and the corpus callosum was examined.

BDNF+/- mice exhibit deficits in oligodendrocyte lineage cells of the basal forebrain.

Previous work indicated that brain-derived neurotrophic factor (BDNF), through the trkB receptor, increases DNA synthesis in oligodendrocyte (OLG) progenitor cells (OPCs) and differentiation of postmitotic OLGs of the basal forebrain (BF). In the present studies, BDNF knockout animals were used to investigate BDNF's effects on OLG lineage cells (OLCs) in vivo. OLCs of the BF were found to express the trkB receptor, suggesting they are responsive to BDNF.