Regulation of hippocampal postnatal and adult neurogenesis by adenosine A2A receptor: interaction with brain ‐derived neurotrophic factor

We showed that A2AR activation enhances hippocampal neurogenesis. This A2AR-mediated neurogenesis was possible through an increase in the self-renewal capacity of Type 1 and Type 2 cells, and through neuronal committed cell protection, neuronal differentiation and neuronal branching. A2AR activation was shown to promote BDNF secretion and extracellular BDNF was essential for A2AR actions. Finally, A2AR endogenous activation was also essential for the BDNF-mediated actions in neuronal differentiation but not for self-renewal capacity. AbstractAdenosine A2A receptor (A2AR) activation modulates several brain processes, ranging from neuronal maturation to synaptic plasticity. Most of these actions occur through the modulation of the actions of the neurotrophin brain-derived neurotrophic factor (BDNF). In this work we studied the role of A2ARs in regulating postnatal and adult neurogenesis in the rat hippocampal dentate gyrus (DG). Here we show that A2AR activation with CGS21680 promoted neural stem cell self-renewal, protected committed neuronal cells from cell death and contributed to a higher density of immature and mature neuronal cells, particularly glutamatergic neurons. Moreover, A2AR endogenous activation was found to be essential for BDNF-mediated increase in cell proliferation and neuronal differentiation. Our findings contribute to further understand the role of adenosinergic signalling in the brain and may have an impact in the development of strategies for brain repai...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research