Year-end Sale % OFF 
Abstract
Several neurodevelopmental disabilities are strongly associated with alterations in GABAergic transmission, and therapies to stimulate its normal development are lacking. Erythropoietin (EPO) is clinically used in neonatology to mitigate acute brain injury, and to stimulate neuronal maturation. Yet it remains unclear whether EPO can stimulate maturation of the GABAergic system. Here, with the use of a transgenic mouse line that constitutively overexpresses neuronal EPO (Tg21), we show that EPO stimulates postnatal GABAergic maturation in the hippocampus. We show an increase in hippocampal GABA-immunoreactive neurons, and postnatal elevation of interneurons expressing parvalbumin (PV), somatostatin (SST), and neuropeptide Y (NPY). Analysis of perineuronal net (PNN) formation and innervation of glutamatergic terminals onto PV+ cells, shows to be enhanced early in postnatal development. Additionally, an increase in GABAAergic synapse density and IPSCs in CA1 pyramidal cells from Tg21 mice is observed. Detection of EPO receptor (EPOR) mRNA was observed to be restricted to glutamatergic pyramidal cells and increased in Tg21 mice at postnatal day (P)7, along with reduced apoptosis. Our findings show that EPO can stimulate postnatal GABAergic maturation in the hippocampus, by increasing neuronal survival, modulating critical plasticity periods, and increasing synaptic transmission. Our data supports EPO's clinical use to balance GABAergic dysfunction.
Highlights
Perinatal brain injury (PBI) might lead to psychiatric disorders associated with alterations in GABAergic transmission (Marin, 2012; Cunha-Rodrigues et al, 2018; Lacaille et al, 2019)
These findings indicate that EPO overexpression accelerates maturation of interneuron subpopulations in a region-specific manner during postnatal development
EPO overexpression in neurons caused a reduction in apoptosis in the CA1 and CA3 hippocampus during the first postnatal week, when EPO receptors (EPORs) were upregulated in principal cells of the Tg21 mice
Summary
Perinatal brain injury (PBI) might lead to psychiatric disorders associated with alterations in GABAergic transmission (Marin, 2012; Cunha-Rodrigues et al, 2018; Lacaille et al, 2019). A significant reduction of several markers of GABAergic transmission, including glutamic acid decarboxylase (GAD), GABA, GABAA receptors (GABAARs), and perturbed parvalbumin (PV) and somatostatin (SST) expression in cortical interneurons, have been reported in the neonatal brain after injury (Robinson et al, 2006; Komitova et al, 2013). Postmortem samples from human preterm infants with brain injury, as well as Received January 7, 2021; accepted January 9, 2021; First published January 25, 2021. The authors declare no competing financial interests.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
