Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury.

Erythropoietin (EPO) exerts potent neuroprotective, neuroregenerative and procognitive functions. However, unequivocal demonstration of erythropoietin receptor (EPOR) expression in brain cells has remained difficult since previously available anti-EPOR antibodies (EPOR-AB) were unspecific. We report here a new, highly specific, polyclonal rabbit EPOR-AB directed against different epitopes in the cytoplasmic tail of human and murine EPOR and its characterization by mass spectrometric analysis of immuno-precipitated endogenous EPOR, Western blotting, immunostaining and flow cytometry. Among others, we applied genetic strategies including overexpression, Lentivirus-mediated conditional knockout of EpoR and tagged proteins, both on cultured cells and tissue sections, as well as intracortical implantation of EPOR-transduced cells to verify specificity. We show examples of EPOR expression in neurons, oligodendroglia, astrocytes and microglia. Employing this new EPOR-AB with double-labeling strategies, we demonstrate membrane expression of EPOR as well as its localization in intracellular compartments such as the Golgi apparatus. Moreover, we show injury-induced expression of EPOR. In mice, a stereotactically applied stab wound to the motor cortex leads to distinct EpoR expression by reactive GFAP-expressing cells in the lesion vicinity. In a patient suffering from epilepsy, neurons and oligodendrocytes of the hippocampus strongly express EPOR. To conclude, this new analytical tool will allow neuroscientists to pinpoint EPOR expression in cells of the nervous system and to better understand its role in healthy conditions, including brain development, as well as under pathological circumstances, such as upregulation upon distress and injury.

Aß38 in the brains of patients with sporadic and familial Alzheimer's disease and transgenic mouse models.

The pathogenesis of Alzheimer's disease (AD) is believed to be closely dependent on deposits of neurotoxic amyloid-ß peptides (Aß), which become abundantly present throughout the central nervous system in advanced stages of the disease. The different Aß peptides existing are generated by subsequent cleavage of the amyloid-ß protein precursor (AßPP) and may vary in length and differ at their C-terminus. Despite extensive studies on the most prevalent species Aß40 and Aß42, Aß peptides with other C-termini such as Aß38 have not received much attention. In the present study, we used a highly specific and sensitive antibody against Aß38 to analyze the distribution of this Aß species in cases of sporadic and familial AD, as well as in the brains of a series of established transgenic AD mouse models. We found Aß38 to be present as vascular deposits in the brains of the majority of sporadic AD cases, whereas it is largely absent in non-demented control cases. Aß38-positive extracellular plaques were virtually limited to familial cases. Interestingly we observed Aß38-positive plaques not only among familial cases due to AßPP mutations, but also in cases of familial AD caused by presenilin (PSEN) mutations. Furthermore we demonstrate that Aß38 deposits in the form of extracellular plaques are common in several AD transgenic mouse models carrying either only AßPP, or combinations of AßPP, PSEN1, and tau transgenes.