Expression patterns of erythropoietin and its receptor in the developing midbrain

Abstract

The expression patterns of erythropoietin (EPO) and its receptor (EPOR) were investigated in the midbrain and in adjacent parts of the synencephalon and hindbrain of embryonic C57Bl mice. On embryonic (E) day 8 (E8), virtually all neuroepithelial cells expressed EPOR. After neural tube closure, subsets of these cells downregulated EPOR. In contrast, radial glial cells were EPOR-immunolabeled from E11 onwards. Simultaneously, subpopulations of early developing neurons upregulated EPO and expressed HIF-1, known to transcriptionally activate EPO. Three-dimensional reconstructions revealed subpopulations of EPO-expressing neurons: (1) in the trigeminal mesencephalic nucleus (TMN), (2) at the rostral transition of the midbrain and synencephalon, (3) in the basal plate of the midbrain, (4) in the trigeminal motor nucleus, and (5) in the trigeminal principal sensory nucleus. In the rostral midbrain and synencephalon, EPO-immunoreactive neurons were attached to EPOR-expressing radial glial cells. The identity of radial glial cells was proven by their immunoreactivity for antibodies against astrocyte-specific glutamate transporter, brain lipid-binding protein, and nestin. From E12.5 onwards EPOR was downregulated in radial glial cells. Viable neurons of the TMN continued to express EPO and upregulated EPOR. Our findings provide new evidence that components of the EPO system are present in distinct locations of the embryonic brain and, by interactions between neurons and radial glial cells as well as among clustered TMN neurons, may contribute to its morphogenesis. Whether the observed expression patterns of EPO and EPOR may reflect EPO-mediated trophic and/or antiapoptotic effects on neurons is discussed.

Early development of the nervous system of the eutherian <i>Tupaia belangeri</i>

“…16). Possible functions of these transverse bands may include boundary formation between developing diencephalic and mesencephalic regions and/or the elimination of precursor cells of the mesencephalic trigeminal nucleus which, in mice, is protected by the embryonic erythropoietin system (Knabe et al, , 2004a.…”

Role of erythropoietin in the brain

“…EPO-R brain expression has been observed during development and adulthood in human and non-human primates and other mammals [10,[23][24][25][26]. In the developing mouse brain during mid gestation, EPO-R localizes in the neural tube in the neuroepithelium that contains proliferating neuroprecursors [8,23].…”

“…EPO also persists in human cerebrospinal fluid after birth and is elevated by hypoxia [47]. In mice, EPO-R is expressed throughout the neural tube in the neuroepithelium by E8.5 and EPO expression follows by 0.5 -1 d, appearing to coincide with HIF-1 expression [8,25]. EPO-R expression in neural crest-and mesenchyme-derived cells around E10 is also followed by EPO expression one day later.…”

“…EPO and EPO-R null mice die around E13.5 due to lack of definitive erythropoiesis [5,6], and prior to death in utero, EPO and EPO-R null mice exhibit a thinning of the neuroepithelium and smaller brain size [7,25]. Mice that lack EPO or EPO-R exhibit incomplete closure of the neural tube at E10.5 when EPO-R is expressed at high levels in wild type mice.…”

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

“…It has been also reported that EPO displays efficient neuroprotective properties in a spectrum of different animal models, including ischemia/hypoxia, excitotoxic paradigms, traumatic brain and spinal cord injury, and retina/optic nerve damage in inflammatory/auto-immunological diseases [7] . Recent studies have revealed a possible protective role of EPO in Parkinson's disease [8][9][10] .…”