Regulation of adult neural progenitor cell functions by purinergic signaling

Abstract

Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells (NSCs) and adult neural progenitor cells (NPCs). Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes. Nucleotides/nucleosides facilitate or inhibit NSC/NPC proliferation, migration and differentiation. The most ubiquitous effect of all agonists (especially of ATP and ADP) appears to be the facilitation of cell proliferation, usually through P2Y1Rs and sometimes through P2X7Rs. However, usually P2X7R activation causes necrosis/apoptosis of NPCs. Differentiation can be initiated by P2Y2R-activation or P2X7R-blockade. A key element in the transduction mechanism of either receptor is the increase of the intracellular free Ca concentration, which may arise due to its release from intracellular storage sites (G protein-coupling; P2Y) or due to its passage through the receptor-channel itself from the extracellular space (ATP-gated ion channel; P2X). Further research is needed to clarify how purinergic signaling controls NSC/NPC fate and how the balance between the quiescent and activated states is established with fine and dynamic regulation. GLIA 2017;65:213-230.

Inflammatory Cytokines Facilitate the Sensitivity of P2X7 Receptors Toward Extracellular ATP at Neural Progenitor Cells of the Rodent Hippocampal Subgranular Zone

“…In conclusion, our in vitro experiments supported the hypothesis that the increased release of ATP from granule cells onto the hippocampal SGZ during a status epilepticus might foster the proliferation of NPCs [2,18]. Subsequently, proliferating NPCs migrate into ectopic locations, differentiate into mature neurons, and become integrated into pathological neuronal circuits.…”

“…In the adult mammalian brain, the subgranular zone (SGZ) of the hippocampal dentate gyrus is one of the regenerative niches where neural progenitor cells (NPCs) are produced to give rise to the three main neural cell linages, i.e., neurons, astrocytes, and oligodendrocytes [1][2][3]. During their integration into the hippocampal circuits, NPCs pass through various consecutive developmental stages before differentiating to newborn and subsequently mature granule cells (glutamatergic projection neurons to CA3 pyramidal neurons).…”

Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury

“…To date, three subtypes of nucleotide receptors have been identified, including the adenosine P1 receptor, the P2X ion channel receptor, and the G protein‐coupled receptor P2Y (Burnstock, ). Accumulating evidence shows that P2X receptor subtypes are widely expressed in the central nervous system, such as in neurons, microglia, astrocytes, and oligodendrocytes, with involvement in synaptic transmission, neuromodulation, and neuroinflammatory response (Burnstock, ; Tang & Illes, ). P2X receptors are upregulated in response to nerve injury.…”

Repurposing Fumaric Acid Esters to Treat Conditions of Oxidative Stress and Inflammation: A Promising Emerging Approach with Broad Potential

“…Collectively, these results support the potential of DMF/ MMF therapy in conditions of neurotoxicity and suggest that its ability to activate HO-1 may be critical. Neural stem/progenitor cells (NPCs) are a heterogeneous population of self-renewing and multi-potent cells that can differentiate into neurons, astrocytes, or oligodendrocytes (post-mitotic daughter cells) [55,56]. Hence, the survival of these cells could greatly impact various forms of neurodegenerative diseases.…”