Tác động của nucleoside purin đến sự dẻo dai của não bộ ở người trưởng thành

Aimone JB, Li Y, Lee SW, Clemenson GD, Deng W, Gage FH (2014) Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev 94(4):991–1026. https://doi.org/10.1152/PHYSREV.00004.2014 Kempermann G, Gage FH (1998) Closer to neurogenesis in adult humans. Nat Med 4(5):555–557. https://doi.org/10.1038/NM0598-555 Rodrigues RJ, Marques JM, Cunha RA (2019) Purinergic signalling and brain development. Semin Cell Dev Biol 95:34–41. https://doi.org/10.1016/J.SEMCDB.2018.12.001 M Puderbaugh and PD Emmady (2023) Neuroplasticity. Treasure Island FL StatPearls. M Jiang, SE Jang, L Zeng (2023) ‘The effects of extrinsic and intrinsic factors on neurogenesis’ Cells 12(9) https://doi.org/10.3390/CELLS12091285. Cramer SC et al (2011) Harnessing neuroplasticity for clinical applications. Brain 134(6):1591–1609. https://doi.org/10.1093/BRAIN/AWR039 Castrén E, Antila H (2017) Neuronal plasticity and neurotrophic factors in drug responses. Mol Psychiatry 22(8):1085–1095. https://doi.org/10.1038/MP.2017.61 Castrén E, Hen R (2013) Neuronal plasticity and antidepressant actions. Trends Neurosci 36(5):259–267. https://doi.org/10.1016/J.TINS.2012.12.010 Gallagher A, Bulteau C, Cohen D, Michaud JL (2019). Neurocognitive Development: Normative Development, vol 173, no 1. Elsevier, pp 2–513 Singh S, Mishra A, Srivastava N, Shukla S (2017) MK-801 (dizocilpine) regulates multiple steps of adult hippocampal neurogenesis and alters psychological symptoms via Wnt/β-catenin signaling in parkinsonian rats. ACS Chem Neurosci 8(3):592–605. https://doi.org/10.1021/ACSCHEMNEURO.6B00354 Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Compar Neurol 124(3):319–335. https://doi.org/10.1002/CNE.901240303 Mokhemer SA, Desouky MK, Abdelghany AK, Ibrahim MFG (2023) Stem cells therapeutic effect in a reserpine-induced fibromyalgia rat model: a possible NLRP3 inflammasome modulation with neurogenesis promotion in the cerebral cortex. Life Sci 325:121784. https://doi.org/10.1016/J.LFS.2023.121784 EP Bless et al. (2016) ‘Adult neurogenesis in the female mouse hypothalamus: estradiol and high-fat diet alter the generation of newborn neurons expressing estrogen receptor α’, eNeuro, 3(4) https://doi.org/10.1523/ENEURO.0027-16.2016 Bernier PJ, Bédard A, Vinet J, Lévesque M, Parent A (2002) Newly generated neurons in the amygdala and adjoining cortex of adult primates. Proc Natl Acad Sci U S A 99(17):11464–11469. https://doi.org/10.1073/PNAS.172403999 Bartkowska K, Turlejski K, Koguc-Sobolewska P, Djavadian R (2023) Adult neurogenesis in the mammalian hypothalamus: impact of newly generated neurons on hypothalamic function. Neuroscience 515:83–92. https://doi.org/10.1016/J.NEUROSCIENCE.2023.02.012 Ribeiro FF, Xapelli S (2021) An overview of adult neurogenesis. Adv Exp Med Biol 1331:77–94. https://doi.org/10.1007/978-3-030-74046-7_7 Denoth-Lippuner A, Jessberger S (2021) Formation and integration of new neurons in the adult hippocampus. Nat Rev Neurosci 22(4):223–236. https://doi.org/10.1038/s41583-021-00433-z Gonçalves JT, Schafer ST, Gage FH (2016) Adult neurogenesis in the hippocampus: from stem cells to behavior. Cell 167(4):897–914. https://doi.org/10.1016/J.CELL.2016.10.021 Waites CL, Craig AM, Garner CC (2005) Mechanisms of vertebrate synaptogenesis. Annu Rev Neurosci 28:251–274. https://doi.org/10.1146/ANNUREV.NEURO.27.070203.144336 KM Harris and SB Kater (1994) ‘Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function’ Annu Rev Neurosci 17 341–371 https://doi.org/10.1146/ANNUREV.NE.17.030194.002013. Lai KO, Ip NY (2013) Structural plasticity of dendritic spines: the underlying mechanisms and its dysregulation in brain disorders. Biochim Biophys Acta Mol Basis Dis 1832(12):2257–2263. https://doi.org/10.1016/J.BBADIS.2013.08.012 Woolfrey KM, Dell’Acqua ML (2015) Coordination of protein phosphorylation and dephosphorylation in synaptic plasticity. J Biol Chem 290(48):28604–28612. https://doi.org/10.1074/JBC.R115.657262 Citri A, Malenka RC (2008) Synaptic Plasticity: Multiple Forms, Functions, and Mechanisms. Neuropsychopharmacology 33(1):18–41. https://doi.org/10.1038/sj.npp.1301559 M Fumagalli, D Lecca, MP Abbracchio, S Ceruti (2017) ‘Pathophysiological role of purines and pyrimidines in neurodevelopment: unveiling new pharmacological approaches to congenital brain diseases’ Front Pharmacol 8 https://doi.org/10.3389/FPHAR.2017.00941. DE Ribeiro, T Glaser, A Oliveira-Giacomelli and H Ulrich (2019) ‘Purinergic receptors in neurogenic processes’ Brain Res Bull 151 3–11 https://doi.org/10.1016/J.BRAINRESBULL.2018.12.013. D Lecca, M Fumagalli, S Ceruti and MP Abbracchio (2016) ‘Intertwining extracellular nucleotides and their receptors with Ca2+ in determining adult neural stem cell survival, proliferation and final fate’ Philos Trans R Soc Lond B Biol Sci 371(1700) https://doi.org/10.1098/RSTB.2015.0433. EK Jackson, D Cheng, TC Jackson, JD Verrier and DG Gillespie (2013) ‘Extracellular guanosine regulates extracellular adenosine levels’, Am J Physiol Cell Physiol 304(5) https://doi.org/10.1152/AJPCELL.00212.2012. Burnstock G (2020) Introduction to purinergic signalling in the brain. Adv Exp Med Biol 1202:1–12. https://doi.org/10.1007/978-3-030-30651-9_1/COVER Burnstock G (2011) Introductory overview of purinergic signalling. Front Biosci Elite 3(3):896–900. https://doi.org/10.2741/E298/PDF Santos TG, Souza DO, Tasca CI (2006) GTP uptake into rat brain synaptic vesicles. Brain Res 1070(1):71–76. https://doi.org/10.1016/J.BRAINRES.2005.10.099 Schmidt AP, Lara DR, Souza DO (2007) Proposal of a guanine-based purinergic system in the mammalian central nervous system. Pharmacol Ther 116(3):401–416. https://doi.org/10.1016/J.PHARMTHERA.2007.07.004 Wong PC, Henderson JF (1972) Purine ribonucleotide biosynthesis, interconversion and catabolism in mouse brain in vitro. Biochem J 129(5):1085–1094. https://doi.org/10.1042/BJ1291085 Burnstock G (2007) Purine and pyrimidine receptors. Cell Mol Life Sci 64(12):1471–1483. https://doi.org/10.1007/S00018-007-6497-0 G Burnstock (2017) ‘Purinergic signalling: therapeutic developments’, Front Pharmacol 8 https://doi.org/10.3389/FPHAR.2017.00661. Burnstock G (2013) Introduction to purinergic signalling in the brain. Adv Exp Med Biol 986:1–12. https://doi.org/10.1007/978-94-007-4719-7_1 Dal-Cim T et al (2013) Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions. J Neurochem 126(4):437–450. https://doi.org/10.1111/JNC.12324 El-Shamarka MES, El-Sahar AE, Saad MA, Assaf N, Sayed RH (2022) Inosine attenuates 3-nitropropionic acid-induced Huntington’s disease-like symptoms in rats via the activation of the A2AR/BDNF/TrKB/ERK/CREB signaling pathway. Life Sci 300:120569. https://doi.org/10.1016/J.LFS.2022.120569 Frinchi M et al (2020) Guanosine-mediated anxiolytic-like effect: interplay with adenosine a1 and a2a receptors. Int J Mol Sci 21(23):1–15. https://doi.org/10.3390/IJMS21239281 IS Kim and EK Jo (2022) Inosine: a bioactive metabolite with multimodal actions in human diseases Front Pharmacol 13 https://doi.org/10.3389/FPHAR.2022.1043970. Palmer TM, Stiles GL (1995) Adenosine receptors. Neuropharmacology 34(7):683–694. https://doi.org/10.1016/0028-3908(95)00044-7 Cunha RA (2016) How does adenosine control neuronal dysfunction and neurodegeneration? J Neurochem 139(6):1019–1055. https://doi.org/10.1111/JNC.13724 Matos M et al (2012) Adenosine A2A receptors modulate glutamate uptake in cultured astrocytes and gliosomes. Glia 60(5):702–716. https://doi.org/10.1002/GLIA.22290 Matos M, Augusto E, MacHado NJ, Dos Santos-Rodrigues A, Cunha RA, Agostinho P (2012) Astrocytic adenosine A2A receptors control the amyloid-β peptide-induced decrease of glutamate uptake. J Alzheim Dis 31(3):555–567. https://doi.org/10.3233/JAD-2012-120469 S Ferré et al (2022) G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs) Pharmacol Ther 231 https://doi.org/10.1016/J.PHARMTHERA.2021.107977. G Navarro et al (2018) Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase Nat Commun 9(1) https://doi.org/10.1038/S41467-018-03522-3. Ciruela F et al (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1–A2A receptor heteromers. J Neurosci 26(7):2080–2087. https://doi.org/10.1523/JNEUROSCI.3574-05.2006 Traversa U, Bombi G, Di Iorio P, Ciccarelli R, Werstiuk ES, Rathbone MP (2002) Specific [(3)H]-guanosine binding sites in rat brain membranes. Br J Pharmacol 135(4):969–976. https://doi.org/10.1038/SJ.BJP.0704542 Volpini R et al (2011) Evidence for the existence of a specific g protein-coupled receptor activated by guanosine. ChemMedChem 6(6):1074–1080. https://doi.org/10.1002/CMDC.201100100 Tasca CI, Lanznaster D, Oliveira KA, Fernández-Dueñas V, Ciruela F (2018) Neuromodulatory effects of guanine-based purines in health and disease. Front Cell Neurosci 12:376. https://doi.org/10.3389/fncel.2018.00376 R Ciccarelli et al 1999 Rat cultured astrocytes release guanine-based purines in basal conditions and after hypoxia/hypoglycemia Glia https://doi.org/10.1002/(SICI)1098-1136(19990101)25:1 Rathbone MP, Middlemiss PJ, de Luca B, Jovetich M (1991) Extracellular guanosine increases astrocyte cAMP: inhibition by adenosine A2 antagonists. NeuroReport 2(11):661–664. https://doi.org/10.1097/00001756-199111000-00007 Rathbone MP, Middlemiss PJ, Gysbers JW, DeForge S, Costello P, Del Maestro RF (1992) Purine nucleosides and nucleotides stimulate proliferation of a wide range of cell types. In Vitro Cell Dev Biol 28A(7–8):529–536. https://doi.org/10.1007/BF02634137 Almeida RF et al (2017) Guanosine anxiolytic-like effect involves adenosinergic and glutamatergic neurotransmitter systems. Mol Neurobiol 54(1):423–436. https://doi.org/10.1007/s12035-015-9660-x Dal-Cim T, Poluceno GG, Lanznaster D, de Oliveira KA, Nedel CB, Tasca CI (2019) Guanosine prevents oxidative damage and glutamate uptake impairment induced by oxygen/glucose deprivation in cortical astrocyte cultures: involvement of A1 and A2A adenosine receptors and PI3K, MEK, and PKC pathways. Purinergic Signal 15(4):465–476. https://doi.org/10.1007/s11302-019-09679-w Dobrachinski F et al (2019) Guanosine Attenuates Behavioral deficits after traumatic brain injury by modulation of adenosinergic receptors. Mol Neurobiol 56(5):3145–3158. https://doi.org/10.1007/S12035-018-1296-1 D Lanznaster et al (2019) Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects Cells 8(12) https://doi.org/10.3390/CELLS8121630. Gomes JI et al (2021) Of adenosine and the blues: the adenosinergic system in the pathophysiology and treatment of major depressive disorder. Pharmacol Res 163:105363. https://doi.org/10.1016/J.PHRS.2020.105363 Parkinson FE et al (2011) Molecular biology of nucleoside transporters and their distributions and functions in the brain. Curr Top Med Chem 11(8):948–972. https://doi.org/10.2174/156802611795347582 N Rotermund, K Schulz, D Hirnet and C Lohr (2019) Purinergic signaling in the vertebrate olfactory system, Front Cell Neurosci 13 https://doi.org/10.3389/FNCEL.2019.00112. R Guinzberg, D Cortés, A Díaz-Cruz, H Riveros-Rosas, R Villalobos-Molina, E Piña (2006) Inosine released after hypoxia activates hepatic glucose liberation through A3 adenosine receptors Am J Physiol Endocrinol Metab 290(5) https://doi.org/10.1152/AJPENDO.00173.2005. Litsky ML, Hohl CM, Lucas JH, Jurkowitz MS (1999) Inosine and guanosine preserve neuronal and glial cell viability in mouse spinal cord cultures during chemical hypoxia. Brain Res 821(2):426–432. https://doi.org/10.1016/S0006-8993(99)01086-0 Jurkowitz MS, Litsky ML, Browning MJ, Hohl CM (1998) Adenosine, inosine, and guanosine protect glial cells during glucose deprivation and mitochondrial inhibition: correlation between protection and ATP preservation. J Neurochem 71(2):535–548. https://doi.org/10.1046/J.1471-4159.1998.71020535.X Böcklinger K, Tomaselli B, Heftberger V, Podhraski V, Bandtlow C, Baier-Bitterlich G (2004) Purine nucleosides support the neurite outgrowth of primary rat cerebellar granule cells after hypoxia. Eur J Cell Biol 83(2):51–54. https://doi.org/10.1078/0171-9335-00362 Haskó G, Sitkovsky MV, Szabó C (2004) Immunomodulatory and neuroprotective effects of inosine. Trends Pharmacol Sci 25(3):152–157. https://doi.org/10.1016/J.TIPS.2004.01.006 Lanznaster D, Dal-Cim T, Piermartiri TCB, Tasca CI (2016) Guanosine: a neuromodulator with therapeutic potential in brain disorders. Aging Dis 7(5):657–679. https://doi.org/10.14336/AD.2016.0208 Grimm I, Ullsperger SN, Zimmermann H (2010) Nucleotides and epidermal growth factor induce parallel cytoskeletal rearrangements and migration in cultured adult murine neural stem cells. Acta Physiol 199(2):181–189. https://doi.org/10.1111/J.1748-1716.2010.02092.X Mishra SK et al (2006) Extracellular nucleotide signaling in adult neural stem cells: synergism with growth factor-mediated cellular proliferation. Development 133(4):675–684. https://doi.org/10.1242/dev.02233 Benito-Muñoz M, Matute C, Cavaliere F (2016) Adenosine A1 receptor inhibits postnatal neurogenesis and sustains astrogliogenesis from the subventricular zone. Glia 64(9):1465–1478. https://doi.org/10.1002/GLIA.23010 Migita H et al (2008) Activation of adenosine A1 receptor-induced neural stem cell proliferation via MEK/ERK and Akt signaling pathways. J Neurosci Res 86(13):2820–2828. https://doi.org/10.1002/JNR.21742 Chauhan G et al (2016) Adenosine A1 receptor antagonist mitigates deleterious effects of sleep deprivation on adult neurogenesis and spatial reference memory in rats. Neuroscience 337:107–116. https://doi.org/10.1016/J.NEUROSCIENCE.2016.09.007 Shukla M et al (2019) Attenuation of adverse effects of noise induced hearing loss on adult neurogenesis and memory in rats by intervention with adenosine A2A receptor agonist. Brain Res Bull 147:47–57. https://doi.org/10.1016/J.BRAINRESBULL.2019.02.006 Oliveros A et al (2017) Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal neuroblast proliferation. Transl Psychiatry 7(4):e1095. https://doi.org/10.1038/TP.2017.64 A Oliveros et al (2022) Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function Proc Natl Acad Sci U S A 119(28) https://doi.org/10.1073/PNAS.2206415119. Horgusluoglu-Moloch E et al (2017) Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 60:92–103. https://doi.org/10.1016/J.NEUROBIOLAGING.2017.08.010 Rampon C, Gauron C, Meda F, Volovitch M, Vriz S (2014) Adenosine enhances progenitor cell recruitment and nerve growth via its A2B receptor during adult fin regeneration. Purinergic Signal 10(4):595–602. https://doi.org/10.1007/S11302-014-9420-9 Thevananther S, Rivera A, Rivkees SA (2001) A1 adenosine receptor activation inhibits neurite process formation by Rho kinase-mediated pathways. NeuroReport 12(14):3057–3063. https://doi.org/10.1097/00001756-200110080-00015 Canals M et al (2005) Molecular mechanisms involved in the adenosine A1 and A 2A receptor-induced neuronal differentiation in neuroblastoma cells and striatal primary cultures. J Neurochem 92(2):337–348. https://doi.org/10.1111/j.1471-4159.2004.02856.x Sun CN et al (2010) The A2A adenosine receptor rescues neuritogenesis impaired by p53 blockage via KIF2A, a kinesin family member. Dev Neurobiol 70(8):604–621. https://doi.org/10.1002/DNEU.20802 Chern Y, Chien T, Fu X, Shah AP, Abel T, Baraban JM (2019) Trax: a versatile signaling protein plays key roles in synaptic plasticity and DNA repair. Neurobiol Learn Mem 159:46. https://doi.org/10.1016/J.NLM.2018.07.003 Ribeiro FF et al (2021) Regulation of hippocampal postnatal and adult neurogenesis by adenosine A2A receptor: Interaction with brain-derived neurotrophic factor. Stem Cells 39(10):1362–1381. https://doi.org/10.1002/STEM.3421 Cheng HC, Shih HM, Chern Y (2002) Essential role of cAMP-response element-binding protein activation by A2A adenosine receptors in rescuing the nerve growth factor-induced neurite outgrowth impaired by blockage of the MAPK cascade. J Biol Chem 277(37):33930–33942. https://doi.org/10.1074/JBC.M201206200 Nakashima KI et al (2018) Stimulation of the adenosine A3 receptor, not the A1 or A2 receptors, promote neurite outgrowth of retinal ganglion cells. Exp Eye Res 170:160–168. https://doi.org/10.1016/J.EXER.2018.02.019 Reis SL, Silva HB, Almeida M, Cunha RA, Simões AP, Canas PM (2019) Adenosine A1 and A2A receptors differently control synaptic plasticity in the mouse dorsal and ventral hippocampus. J Neurochem 151(2):227–237. https://doi.org/10.1111/JNC.14816 Xia J et al (2009) Activity-dependent release of adenosine inhibits the glutamatergic synaptic transmission and plasticity in the hypothalamic hypocretin/orexin neurons. Neuroscience 162(4):980–988. https://doi.org/10.1016/J.NEUROSCIENCE.2009.05.033 Moore KA, Nicoll RA, Schmitz D (2003) Adenosine gates synaptic plasticity at hippocampal mossy fiber synapses. Proc Natl Acad Sci U S A 100(24):14397. https://doi.org/10.1073/PNAS.1835831100 SP Perrier, M Gleizes, C Fonta, LG Nowak (2019) Effect of adenosine on short-term synaptic plasticity in mouse piriform cortex in vitro: adenosine acts as a high-pass filter Physiol Rep 7(3) https://doi.org/10.14814/PHY2.13992. Costenla AR, De Mendonça A, Ribeiro JA (1999) Adenosine modulates synaptic plasticity in hippocampal slices from aged rats. Brain Res 851(1–2):228–234. https://doi.org/10.1016/S0006-8993(99)02194-0 Fanselow MS, Dong HW (2010) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65(1):7–19. https://doi.org/10.1016/J.NEURON.2009.11.031 D Madeira, CR Lopes, AP Simões, PM Canas, RA Cunha and P Agostinho (2023) Astrocytic A2A receptors silencing negatively impacts hippocampal synaptic plasticity and memory of adult mice Glia 71(9) https://doi.org/10.1002/GLIA.24384. Costenla AR, Lopes LV, De Mendonça A, Ribeiro JA (2001) A functional role for adenosine A3 receptors: modulation of synaptic plasticity in the rat hippocampus. Neurosci Lett 302(1):53–57. https://doi.org/10.1016/S0304-3940(01)01633-0 Xia JX, Xiong JX, Wang HK, Duan SM, Ye JN, Hu ZA (2012) Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons. Neuroscience 201:46–56. https://doi.org/10.1016/J.NEUROSCIENCE.2011.11.019 Flajolet M et al (2008) FGF acts as a co-transmitter through Adenosine A2A receptor to regulate morphological and physiological synaptic plasticity. Nat Neurosci 11(12):1402. https://doi.org/10.1038/NN.2216 Moscoso-Castro M, López-Cano M, Gracia-Rubio I, Ciruela F, Valverde O (2017) Cognitive impairments associated with alterations in synaptic proteins induced by the genetic loss of adenosine A2A receptors in mice. Neuropharmacology 126:48–57. https://doi.org/10.1016/J.NEUROPHARM.2017.08.027 Ruhal P, Dhingra D (2018) Inosine improves cognitive function and decreases aging-induced oxidative stress and neuroinflammation in aged female rats. Inflammopharmacology 26(5):1317–1329. https://doi.org/10.1007/S10787-018-0476-Y E Samami, E Aleebrahim-Dehkordi, M Mohebalizadeh, S Yaribash, A Saghazadeh and N Rezaei (2023) Inosine, gut microbiota, and cancer immunometabolism Am J Physiol Endocrinol Metab 324(1) https://doi.org/10.1152/AJPENDO.00207.2022. Mager LF et al (2020) Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science 369(6510):1481–1489. https://doi.org/10.1126/SCIENCE.ABC3421 Lima GF et al (2020) Inosine, an endogenous purine nucleoside, avoids early stages of atherosclerosis development associated to eNOS activation and p38 MAPK/NF-kB inhibition in rats. Eur J Pharmacol 882:173289. https://doi.org/10.1016/J.EJPHAR.2020.173289 Welihinda AA, Kaur M, Greene K, Zhai Y, Amento EP (2016) The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias. Cell Signal 28(6):552–560. https://doi.org/10.1016/J.CELLSIG.2016.02.010 Wu Z et al (2008) Reduced cell death by inosine pretreatment after photochemically induced cerebral ischemia in adult rats. Prog Nat Sci 18(12):1513–1518. https://doi.org/10.1016/J.PNSC.2008.03.032 Cipriani S, Bakshi R, Schwarzschild MA (2014) Protection by inosine in a cellular model of Parkinson’s disease. Neuroscience 274:242–249. https://doi.org/10.1016/J.NEUROSCIENCE.2014.05.038 Markowitz CE et al (2009) The Treatment of Multiple Sclerosis with Inosine. J Altern Complement Med 15(6):619. https://doi.org/10.1089/ACM.2008.0513 Doyle C, Cristofaro V, Sullivan MP, Adam RM (2018) Inosine - a multifunctional treatment for complications of neurologic injury. Cell Physiol Biochem 49(6):2293–2303. https://doi.org/10.1159/000493831 Benowitz LI, Goldberg DE, Madsen JR, Soni D, Irwin N (1999) Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury. Proc Natl Acad Sci U S A 96(23):13486–13490. https://doi.org/10.1073/PNAS.96.23.13486 Kuricova M et al (2014) Oral administration of inosine promotes recovery after experimental spinal cord injury in rat. Neurol Sci 35(11):1785–1791. https://doi.org/10.1007/S10072-014-1840-3/FIGURES/5 Smith JM et al (2007) Inosine promotes recovery of skilled motor function in a model of focal brain injury. Brain 130(Pt 4):915–925. https://doi.org/10.1093/BRAIN/AWL393 L Zai et al (2009) Development/plasticity/repair inosine alters gene expression and axonal projections in neurons contralateral to a cortical infarct and improves skilled use of the impaired limb https://doi.org/10.1523/JNEUROSCI.0414-09.2009. Valada P et al (2023) The impact of inosine on hippocampal synaptic transmission and plasticity involves the release of adenosine through equilibrative nucleoside transporters rather than the direct activation of adenosine receptors. Purinergic Signal 19(2):451–461. https://doi.org/10.1007/S11302-022-09899-7 Ciccarelli R et al (2007) Molecular signalling mediating the protective effect of A1 adenosine and mGlu3 metabotropic glutamate receptor activation against apoptosis by oxygen/glucose deprivation in cultured astrocytes. Mol Pharmacol 71(5):1369–1380. https://doi.org/10.1124/MOL.106.031617 Decker H et al (2019) Guanosine and GMP increase the number of granular cerebellar neurons in culture: dependence on adenosine A2A and ionotropic glutamate receptors. Purinergic Signal 15(4):439. https://doi.org/10.1007/S11302-019-09677-Y Deutsch SI, Rosse RB, Long KD, Gaskins BL, Mastropaolo J (2008) Guanosine possesses specific modulatory effects on NMDA receptor-mediated neurotransmission in intact mice. Eur Neuropsychopharmacol 18(4):299–302. https://doi.org/10.1016/J.EURONEURO.2007.07.010 Porciúncula LO, Vinadé L, Wofchuk S, Souza DO (2002) Guanine based purines inhibit [3H]glutamate and [3H]AMPA binding at postsynaptic densities from cerebral cortex of rats. Brain Res 928(1–2):106–112. https://doi.org/10.1016/S0006-8993(01)03368-6 TCB Piermartiri, B Dos Santos, FGQ Barros-Aragão, RD Prediger, CI Tasca (2020) Guanosine promotes proliferation in neural stem cells from hippocampus and neurogenesis in adult mice https://doi.org/10.1007/s12035-020-01977-4/Published. Su C, Wang P, Jiang C, Ballerini P, Caciagli F, Rathbone P, Jiang S (2013) Guanosine promotes proliferation of neural stem cells through cAMP-CREB pathway. J Biol Regul Homeost Agents 27(3):673–680 Guarnieri S et al (2009) Extracellular guanosine and GTP promote expression of differentiation markers and induce S-phase cell-cycle arrest in human SH-SY5Y neuroblastoma cells. Int J Dev Neurosci 27(2):135–147. https://doi.org/10.1016/J.IJDEVNEU.2008.11.007 Bettio LEB et al (2016) The antidepressant-like effect of chronic guanosine treatment is associated with increased hippocampal neuronal differentiation. Eur J Neurosci 43(8):1006–1015. https://doi.org/10.1111/EJN.13172 Deng G, Qiu Z, Li D, Fang Y, Zhang S (2017) Delayed administration of guanosine improves long-term functional recovery and enhances neurogenesis and angiogenesis in a mouse model of photothrombotic stroke. Mol Med Rep 15(6):3999–4004. https://doi.org/10.3892/MMR.2017.6521 Su C et al (2009) Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis in rats with parkinsonism. J Neurosci Res 87(3):617–625. https://doi.org/10.1002/JNR.21883 Jiang S et al (2003) Guanosine promotes myelination and functional recovery in chronic spinal injury. NeuroReport 14(18):2463–2467. https://doi.org/10.1097/00001756-200312190-00034 Bau C et al (2005) Guanosine stimulates neurite outgrowth in PC12 cells via activation of heme oxygenase and cyclic GMP. Purinergic Signal 1(2):161–172. https://doi.org/10.1007/S11302-005-6214-0 Gysbers JW, Rathbone MP (1996) Neurite outgrowth in PC12 cells is enhanced by guanosine through both cAMP-dependent and -independent mechanisms. Neurosci Lett 220(3):175–178. https://doi.org/10.1016/S0304-3940(96)13253-5 Rathbone MP et al (1999) Trophic effects of purines in neurons and glial cells. Prog Neurobiol 59(6):663–690. https://doi.org/10.1016/S0301-0082(99)00017-9 Ciccarelli R et al (2001) Involvement of astrocytes in purine-mediated reparative processes in the brain. Int J Dev Neurosci 19(4):395–414. https://doi.org/10.1016/S0736-5748(00)00084-8 Middlemiss PJ, Gysbers JW, Rathbone MP (1995) Extracellular guanosine and guanosine-5’-triphosphate increase: NGF synthesis and release from cultured mouse neopallial astrocytes. Brain Res 677(1):152–156. https://doi.org/10.1016/0006-8993(95)00156-K Decker H et al (2007) Guanine derivatives modulate extracellular matrix proteins organization and improve neuron-astrocyte co-culture. J Neurosci Res 85(9):1943–1951. https://doi.org/10.1002/JNR.21332 Gerrikagoitia I, Martínez-Millán L (2009) Guanosine-induced synaptogenesis in the adult brain in vivo. Anat Rec (Hoboken) 292(12):1968–1975. https://doi.org/10.1002/AR.20999 Rosa PB et al (2021) Antidepressant-like effect of guanosine involves activation of AMPA receptor and BDNF/TrkB signaling. Purinergic Signal 17(2):285–301. https://doi.org/10.1007/S11302-021-09779-6 Li X, Jia Z, Yan Y (2022) Ticagrelor for prevention of stroke and cognitive impairment in patients with vascular high-risk factors: a meta-analysis of randomized controlled trials. Int J Cardiol 353:96–102. https://doi.org/10.1016/j.ijcard.2022.01.060 Kovalenko AL et al (2023) Results of a clinical and experimental study of the safety and efficacy of Cytoflavin in combination with reperfusion therapy for ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova 123(8):75–81. https://doi.org/10.17116/JNEVRO202312308175 Schwarzschild MA et al (2021) Effect of urate-elevating inosine on early Parkinson disease progression: the SURE-PD3 randomized clinical trial. JAMA 326(10):926–939. https://doi.org/10.1001/JAMA.2021.10207 Walk D et al (2023) Randomized trial of inosine for urate elevation in amyotrophic lateral sclerosis. Muscle Nerve 67(5):378–386. https://doi.org/10.1002/MUS.27807 Paganoni S et al (2012) Uric acid levels predict survival in men with amyotrophic lateral sclerosis. J Neurol 259(9):1923–1928. https://doi.org/10.1007/S00415-012-6440-7 D Hooper Inosine in the over-the-counter treatment of MS Accessed: Aug. 15, 2023. [Online]. Available: https://grantome.com/grant/NIH/R21-AT001301-02 Wada Y, Hasegawa H, Nakamura M, Yamaguchi N (1992) Anticonvulsant effect of allopurinol on hippocampal-kindled seizures. Pharmacol Biochem Behav 42(4):899–901. https://doi.org/10.1016/0091-3057(92)90046-I Brunstein MG, Ghisolfi ES, Ramos FLP, Lara DR (2005) A clinical trial of adjuvant allopurinol therapy for moderately refractory schizophrenia. J Clin Psychiatry 66(2):213–219. https://doi.org/10.4088/JCP.V66N0209 Dickerson FB et al (2009) A double-blind trial of adjunctive allopurinol for schizophrenia. Schizophr Res 109(1–3):66–69. https://doi.org/10.1016/j.schres.2008.12.028 Buie LW, Oertel MD, Cala SO (2006) Allopurinol as adjuvant therapy in poorly responsive or treatment refractory schizophrenia. Ann Pharmacother 40(12):2200–2204. https://doi.org/10.1345/aph.1H222 Weiser M et al (2012) A randomized controlled trial of allopurinol vs. placebo added on to antipsychotics in patients with schizophrenia or schizoaffective disorder. Schizophr Res 138(1):35–38. https://doi.org/10.1016/j.schres.2012.02.014 Lara DR, Cruz MRS, Xavier F, Souza DO, Moriguchi EH (2003) Allopurinol for the treatment of aggressive behaviour in patients with dementia. Int Clin Psychopharmacol 18(1):53–55. https://doi.org/10.1097/00004850-200301000-00009 Lara DR, Belmonte-de-Abreu P, Souza DO (2000) Allopurinol for refractory aggression and self-inflicted behaviour. J Psychopharmacol 14(1):81–83. https://doi.org/10.1177/026988110001400112 Machado-Vieira R, Lara DR, Souza DO, Kapczinski F (2001) Therapeutic efficacy of allopurinol in mania associated with hyperuricemia. J Clin Psychopharmacol 21(6):621–622. https://doi.org/10.1097/00004714-200112000-00017 Weiser M et al (2014) Allopurinol for mania: a randomized trial of allopurinol versus placebo as add-on treatment to mood stabilizers and/or antipsychotic agents in manic patients with bipolar disorder. Bipolar Disord 16(4):441–447. https://doi.org/10.1111/bdi.12202