The impact of purine nucleosides on neuroplasticity in the adult brain

Abstract

Neuroplasticity refers to the nervous system's ability to adapt and reorganize its cell structures and neuronal networks in response to internal and external stimuli. In adults, this process involves neurogenesis, synaptogenesis, and synaptic and neurochemical plasticity. Several studies have reported the significant impact of the purinergic system on neuroplasticity modulation. And, there is considerable evidence supporting the role of purine nucleosides, such as adenosine, inosine, and guanosine, in this process. This review presents extensive research on how these nucleosides enhance the neuroplasticity of the adult central nervous system, particularly in response to damage. The mechanisms through which these nucleosides exert their effects involve complex interactions with various receptors and signaling pathways. Adenosine's influence on neurogenesis involves interactions with adenosine receptors, specifically A1R and A2AR. A1R activation appears to inhibit neuronal differentiation and promote astrogliogenesis, while A2AR activation supports neurogenesis, neuritogenesis, and synaptic plasticity. Inosine and guanosine positively impact cell proliferation, neurogenesis, and neuritogenesis. Inosine seems to modulate extracellular adenosine levels, and guanosine might act through interactions between purinergic and glutamatergic systems. Additionally, the review discusses the potential therapeutic implications of purinergic signaling in neurodegenerative and neuropsychiatric diseases, emphasizing the importance of these nucleosides in the neuroplasticity of brain function and recovery.

Keywords: Adenosine; Guanosine; Inosine; Neurogenesis; Neuroplasticity; Purine nucleosides; Synaptogenesis.

Fig. 1

Schematic summary of adenosine (ADO) effects on adult brain neuroplasticity. ADO modulates the proliferation of Neural stem cells (NSCs) and Intermediate progenitor cells (IPCs); promotes neurogenesis, synaptogenesis and modulates synaptic plasticity. The effects of ADO on neurogenesis and synaptic plasticity rely on ADO levels and involve a complex interplay of adenosine receptors, particularly A1R and A2AR. Different studies obtained conflicting results depending on the protocols applied, which resulted in similar effects with A1R or A2AR agonists and antagonists. Detailed effects and references are outlined in Table 1. The figure was created using BioRender.com

Fig. 2

Illustration of inosine (INO)-induced neuroplasticity. INO exhibits neuroprotective and neurotrophic effects. Studies indicate INO’s role in promoting neuritogenesis, enhancing neuronal survival, and increasing axonal sprouting. Detailed effects of INO and corresponding references are provided in Table 2. This figure was created using BioRender.com

Fig. 3

Schematic depiction of guanosine (GUO)-induced neuroplasticity. GUO promotes the proliferation of neural stem cells (NSCs), astrocytes, oligodendroglia progenitor cells (OPCs), and intermediate progenitor cells. GUO induces neurogenesis, enhances neuronal survival, promotes neurite outgrowth, and enhances synaptic plasticity. Details regarding effects and references can be found in Table 3. This figure was generated using BioRender.com