Erythropoietin affects GABAergic transmission in hippocampal neurons in vitro

Abstract

Erythropoietin is a potent regulator of erythropoiesis. It acts via the specific membrane receptor (EpoR). Erythropoietin is also known to be present in the central nervous system, and its concentration and the expression of EpoR change during development, which raises the possibility that this modulator might be involved in the regulation of neuronal functions in the developing brain. The GABAergic system undergoes profound changes during development and is particularly susceptible to modulation by endogenous factors. Therefore, we decided to investigate the impact of Epo on GABAergic transmission in hippocampal neurons developing in vitro. An analysis of miniature IPSCs (mIPSCs) revealed that a long-term treatment with Epo (48 or 72 h) resulted in a major acceleration of the decaying phase of these currents while the amplitude and current frequency remained unchanged. Interestingly, this effect was restricted to the youngest considered age group (6-8 DIV), indicating that Epomediated modulation of mIPSCs depends on the developmental stage of the neurons. We conclude that Epo may exert a modulatory action on GABAergic transmission in developing neural networks.

Erythropoietin: a novel therapy for hypoxic–ischaemic encephalopathy?

“…Glutamate is the primary excitatory neurotransmitter in the brain, and plays a significant role in energy failure and apoptotic cell death after hypoxia–ischaemia. EPO has been found to protect neurons from excitotoxic injury in vitro and in vivo . EPO has also been shown to restore antioxidant defences in neonatal HIE …”

The Protective Role of Erythropoietin in the Developing Brain

“…The GABAergic system undergoes profound changes during development and is particularly susceptible to modulation by endogenous factors. In cultured cells, Epo exerts a modulatory action on GABAergic transmission of the development of hippocampal neurons (Wójtowicz & Mozrzymas, 2008). In newborn rats, Epo can completely abolished neuronal degeneration associated with the GABA-mimetic agent propofol administration (Zacharias et al, 2010).…”

Contradictory effects of erythropoietin on inhibitory synaptic transmission in left and right prelimbic cortex of mice

“…On the other hand, published data have also shown that EPO attenuates the excitatory synaptic transmission ( Adamcio et al, 2008 ; Almaguer-Melian et al, 2016 ; Kamal et al, 2011 ), whereas the inhibitory synaptic transmission was found to be facilitated ( Adamcio et al, 2008 ; Wójtowicz and Mozrzymas, 2008 ), and short- and long-term synaptic plasticity was enhanced by EPO in the hippocampus ( Adamcio et al, 2008 ; Kamal et al, 2011 ; Wójtowicz and Mozrzymas, 2008 ). In addition, EPO prevents the effect of chronic restraint stress in male rats ( Aalling et al, 2018 ).…”

“…In summary, the currently available data clearly indicate that EPO can improve cognitive function of mammals by directly acting on the brain, although there are still many discrepancies between different studies whether the cellular effects of EPO are just long-term consequences of erythropoiesis ( Adamcio et al, 2008 ; Kamal et al, 2011 ; Wójtowicz and Mozrzymas, 2008 ). It has been suggested that the divergences of different studies take root in different in-vivo application schemata or in long-term trophic effects of EPO ( Adamcio et al, 2008 ; Kamal et al, 2011 ; Wójtowicz and Mozrzymas, 2008 ). Our previous data showed EPO effects in hippocampus two weeks after in-vivo application ( Adamcio et al, 2008 ; Wójtowicz and Mozrzymas, 2008 ).…”

“…It has been suggested that the divergences of different studies take root in different in-vivo application schemata or in long-term trophic effects of EPO ( Adamcio et al, 2008 ; Kamal et al, 2011 ; Wójtowicz and Mozrzymas, 2008 ). Our previous data showed EPO effects in hippocampus two weeks after in-vivo application ( Adamcio et al, 2008 ; Wójtowicz and Mozrzymas, 2008 ). In the current study, we investigated the direct effects of EPO on inhibitory transmission in the left and the right PrL of mice.…”