Erythropoietin Pathway: A Potential Target for the Treatment of Depression

Abstract

During the past decade, accumulating evidence from both clinical and experimental studies has indicated that erythropoietin may have antidepressant effects. In addition to the kidney and liver, many organs have been identified as secretory tissues for erythropoietin, including the brain. Its receptor is expressed in cerebral and spinal cord neurons, the hypothalamus, hippocampus, neocortex, dorsal root ganglia, nerve axons, and Schwann cells. These findings may highlight new functions for erythropoietin, which was originally considered to play a crucial role in the progress of erythroid differentiation. Erythropoietin and its receptor signaling through JAK2 activate multiple downstream signaling pathways including STAT5, PI3K/Akt, NF-κB, and MAPK. These factors may play an important role in inflammation and neuroprogression in the nervous system. This is particularly true for the hippocampus, which is possibly related to learning, memory, neurocognitive deficits and mood alterations. Thus, the influence of erythropoietin on the downstream pathways known to be involved in the treatment of depression makes the erythropoietin-related pathway an attractive target for the development of new therapeutic approaches. Focusing on erythropoietin may help us understand the pathogenic mechanisms of depression and the molecular basis of its treatment.

Erythropoietin preparation drastically improved activities of daily living in a patient with severe dementia

“…These effects appear in a relatively short period. Some articles have reported that the effects appear 3 or 4 days after EPO administration in experiments with animals or humans . In our case, we concluded that the activities of daily living had improved immediately due to the antidepressant effects of EPO, and earlier than the improvement in anemia.…”

“…As it promotes hematopoiesis, it is clinically used for renal anemia. In recent years, EPO receptors have been detected in the central nervous system; EPO activate multiple downstream signaling pathways and this activation may develop antidepressant effects . These effects appear in a relatively short period.…”

HIF‐1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa

“…DMOG also prevented microglial and glial activation (Iba-1 and GFAP immunolabeling). Although we have not evaluated it, other researchers have shown that HIF-1a and its targets (e.g., erythropoietin) can exert antiapoptotic and anti-inflammatory effects through ERK-1/2 signaling and activation of PKB pathway (55)(56)(57)(58). Further studies are needed to clarify the molecular mechanisms underlying the neuroprotective effect of DMOG.…”

Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin

“…EPO can phosphorylate Akt at serine 473 to activate Akt (37, 64, 87, 88). EPO signaling through Akt activation has been shown to protect against hypoxia-reoxygenation stress (79) and EPO may control intracellular calcium levels to preserve mitochondrial function (31, 67, 89–91).…”