Guanosine fast onset antidepressant-like effects in the olfactory bulbectomy mice model.
Anhedonia
/ drug effects
Animals
Antidepressive Agents
/ adverse effects
Behavior, Animal
/ drug effects
Depressive Disorder, Major
/ drug therapy
Disease Models, Animal
Excitatory Amino Acid Agents
/ pharmacology
Guanosine
/ adverse effects
Ketamine
/ pharmacology
Male
Memory Disorders
/ chemically induced
Mice
Mice, Inbred C57BL
Olfactory Bulb
/ surgery
TOR Serine-Threonine Kinases
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 05 2020
21 05 2020
Historique:
received:
24
12
2019
accepted:
28
04
2020
entrez:
23
5
2020
pubmed:
23
5
2020
medline:
15
12
2020
Statut:
epublish
Résumé
The treatment of major depressive disorder (MDD) is still a challenge. In the search for novel antidepressants, glutamatergic neuromodulators have been investigated as possible fast-acting antidepressants. Innovative studies suggest that the purine cycle and/or the purinergic signaling can be dysregulated in MDD, and the endogenous nucleoside guanosine has gained attention due to its extracellular effects. This study aimed to verify if guanosine produces fast-onset effects in the well-validated, reliable and sensitive olfactory bulbectomy (OBX) model of depression. The involvement of the mTOR pathway, a key target for the fast-onset effect of ketamine, was also investigated. Results show that a single i.p. injection of guanosine, or ketamine, completely reversed the OBX-induced anhedonic-like behavior 24 or 48 h post treatment, as well as the short-term recognition memory impairment 48 h post treatment. The antidepressant-like effects of guanosine and ketamine were completely abolished by rapamycin. This study shows, for the first time, that guanosine, in a way similar to ketamine, is able to elicit a fast antidepressant response in the OBX model in mice. The results support the notion that guanosine represents a new road for therapeutic improvement in MDD.
Identifiants
pubmed: 32439951
doi: 10.1038/s41598-020-65300-w
pii: 10.1038/s41598-020-65300-w
pmc: PMC7242421
doi:
Substances chimiques
Antidepressive Agents
0
Excitatory Amino Acid Agents
0
Guanosine
12133JR80S
Ketamine
690G0D6V8H
mTOR protein, mouse
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8429Références
Park, L. T. & Zarate, C. A. Jr. Depression in the Primary Care Setting. The New England journal of medicine 380, 559–568, https://doi.org/10.1056/NEJMcp1712493 (2019).
doi: 10.1056/NEJMcp1712493
pubmed: 30726688
pmcid: 6727965
Vos, T. et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2163–2196, https://doi.org/10.1016/S0140-6736(12)61729-2 (2012).
doi: 10.1016/S0140-6736(12)61729-2
pubmed: 23245607
pmcid: 6350784
Lee, R. S., Hermens, D. F., Porter, M. A. & Redoblado-Hodge, M. A. A meta-analysis of cognitive deficits in first-episode Major Depressive Disorder. Journal of affective disorders 140, 113–124, https://doi.org/10.1016/j.jad.2011.10.023 (2012).
doi: 10.1016/j.jad.2011.10.023
pubmed: 22088608
Kraus, C., Kadriu, B., Lanzenberger, R., Zarate, C. A. Jr. & Kasper, S. Prognosis and improved outcomes in major depression: a review. Translational psychiatry 9, 127, https://doi.org/10.1038/s41398-019-0460-3 (2019).
doi: 10.1038/s41398-019-0460-3
pubmed: 30944309
pmcid: 6447556
Balestri, M. et al. Socio-demographic and clinical predictors of treatment resistant depression: A prospective European multicenter study. Journal of affective disorders 189, 224–232, https://doi.org/10.1016/j.jad.2015.09.033 (2016).
doi: 10.1016/j.jad.2015.09.033
pubmed: 26451508
Machado-Vieira, R., Henter, I. D. & Zarate, C. A., Jr. New targets for rapid antidepressant action. Prog Neurobiol, https://doi.org/10.1016/j.pneurobio.2015.12.001 (2015).
Kupfer, D. J., Frank, E. & Phillips, M. L. Major depressive disorder: new clinical, neurobiological, and treatment perspectives. Lancet 379, 1045–1055, https://doi.org/10.1016/S0140-6736(11)60602-8 (2012).
doi: 10.1016/S0140-6736(11)60602-8
pubmed: 22189047
Hendrie, C., Pickles, A., Stanford, S. C. & Robinson, E. The failure of the antidepressant drug discovery process is systemic. Journal of psychopharmacology 27, 407–413, discussion 413–406, https://doi.org/10.1177/0269881112466185 (2013).
Ramaker, M. J. & Dulawa, S. C. Identifying fast-onset antidepressants using rodent models. Molecular psychiatry 22, 656–665, https://doi.org/10.1038/mp.2017.36 (2017).
doi: 10.1038/mp.2017.36
pubmed: 28322276
Zarate, C. A. Jr. et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of general psychiatry 63, 856–864, https://doi.org/10.1001/archpsyc.63.8.856 (2006).
doi: 10.1001/archpsyc.63.8.856
pubmed: 16894061
Camargo, A. et al. Augmentation effect of ketamine by guanosine in the novelty-suppressed feeding test is dependent on mTOR signaling pathway. Journal of psychiatric research 115, 103–112, https://doi.org/10.1016/j.jpsychires.2019.05.017 (2019).
doi: 10.1016/j.jpsychires.2019.05.017
pubmed: 31128500
Li, N. et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329, 959–964, https://doi.org/10.1126/science.1190287 (2010).
doi: 10.1126/science.1190287
pubmed: 20724638
pmcid: 3116441
Zanos, P. et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature 533, 481–486, https://doi.org/10.1038/nature17998 (2016).
doi: 10.1038/nature17998
pubmed: 27144355
pmcid: 4922311
Ali-Sisto, T. et al. Purine metabolism is dysregulated in patients with major depressive disorder. Psychoneuroendocrinology 70, 25–32, https://doi.org/10.1016/j.psyneuen.2016.04.017 (2016).
doi: 10.1016/j.psyneuen.2016.04.017
pubmed: 27153521
Ortiz, R., Ulrich, H., Zarate, C. A. Jr. & Machado-Vieira, R. Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics. Progress in neuro-psychopharmacology & biological psychiatry 57, 117–131, https://doi.org/10.1016/j.pnpbp.2014.10.016 (2015).
doi: 10.1016/j.pnpbp.2014.10.016
Kesebir, S., Tatlidil Yaylaci, E., Suner, O. & Gultekin, B. K. Uric acid levels may be a biological marker for the differentiation of unipolar and bipolar disorder: the role of affective temperament. Journal of affective disorders 165, 131–134, https://doi.org/10.1016/j.jad.2014.04.053 (2014).
doi: 10.1016/j.jad.2014.04.053
pubmed: 24882190
Tasca, C. I., Lanznaster, D., Oliveira, K. A., Fernandez-Duenas, V. & Ciruela, F. Neuromodulatory Effects of Guanine-Based Purines in Health and Disease. Frontiers in cellular neuroscience 12, 376, https://doi.org/10.3389/fncel.2018.00376 (2018).
doi: 10.3389/fncel.2018.00376
pubmed: 30459558
pmcid: 6232889
Burnstock, G., Krugel, U., Abbracchio, M. P. & Illes, P. Purinergic signalling: from normal behaviour to pathological brain function. Prog Neurobiol 95, 229–274, https://doi.org/10.1016/j.pneurobio.2011.08.006 (2011).
doi: 10.1016/j.pneurobio.2011.08.006
pubmed: 21907261
Schmidt, A. P., Lara, D. R. & Souza, D. O. Proposal of a guanine-based purinergic system in the mammalian central nervous system. Pharmacology & therapeutics 116, 401–416, https://doi.org/10.1016/j.pharmthera.2007.07.004 (2007).
doi: 10.1016/j.pharmthera.2007.07.004
Di Liberto, V. et al. The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation. Frontiers in pharmacology 7, 158, https://doi.org/10.3389/fphar.2016.00158 (2016).
doi: 10.3389/fphar.2016.00158
pubmed: 27378923
pmcid: 4911385
Bettio, L. E., Gil-Mohapel, J. & Rodrigues, A. L. Guanosine and its role in neuropathologies. Purinergic signalling, https://doi.org/10.1007/s11302-016-9509-4 (2016).
Bettio, L. E. et al. Guanosine produces an antidepressant-like effect through the modulation of NMDA receptors, nitric oxide-cGMP and PI3K/mTOR pathways. Behavioural brain research 234, 137–148, https://doi.org/10.1016/j.bbr.2012.06.021 (2012).
doi: 10.1016/j.bbr.2012.06.021
pubmed: 22743004
Bettio, L. E. et al. Guanosine prevents behavioral alterations in the forced swimming test and hippocampal oxidative damage induced by acute restraint stress. Pharmacology, biochemistry, and behavior 127, 7–14, https://doi.org/10.1016/j.pbb.2014.10.002 (2014).
doi: 10.1016/j.pbb.2014.10.002
pubmed: 25316306
Nestler, E. J. & Hyman, S. E. Animal models of neuropsychiatric disorders. Nat Neurosci 13, 1161–1169, https://doi.org/10.1038/nn.2647 (2010).
doi: 10.1038/nn.2647
pubmed: 20877280
pmcid: 3750731
Czeh, B., Fuchs, E., Wiborg, O. & Simon, M. Animal models of major depression and their clinical implications. Progress in neuro-psychopharmacology & biological psychiatry 64, 293–310, https://doi.org/10.1016/j.pnpbp.2015.04.004 (2015).
doi: 10.1016/j.pnpbp.2015.04.004
Kadriu, B. et al. Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments. The international journal of neuropsychopharmacology 22, 119–135, https://doi.org/10.1093/ijnp/pyy094 (2019).
doi: 10.1093/ijnp/pyy094
pubmed: 30445512
Almeida, R. F. et al. Olfactory bulbectomy in mice triggers transient and long-lasting behavioral impairments and biochemical hippocampal disturbances. Progress in neuro-psychopharmacology & biological psychiatry 76, 1–11, https://doi.org/10.1016/j.pnpbp.2017.02.013 (2017).
doi: 10.1016/j.pnpbp.2017.02.013
Berman, R. M. et al. Antidepressant effects of ketamine in depressed patients. Biological psychiatry 47, 351–354 (2000).
doi: 10.1016/S0006-3223(99)00230-9
Bettio, L. E. et al. The antidepressant-like effect of chronic guanosine treatment is associated with increased hippocampal neuronal differentiation. Eur J Neurosci 43, 1006–1015, https://doi.org/10.1111/ejn.13172 (2016).
doi: 10.1111/ejn.13172
pubmed: 26779605
Hogan-Cann, A. D. & Anderson, C. M. Physiological Roles of Non-Neuronal NMDA Receptors. Trends in pharmacological sciences 37, 750–767, https://doi.org/10.1016/j.tips.2016.05.012 (2016).
doi: 10.1016/j.tips.2016.05.012
pubmed: 27338838
Bliss, T. V. & Collingridge, G. L. Expression of NMDA receptor-dependent LTP in the hippocampus: bridging the divide. Molecular brain 6, 5, https://doi.org/10.1186/1756-6606-6-5 (2013).
doi: 10.1186/1756-6606-6-5
pubmed: 23339575
pmcid: 3562207
Danysz, W., Zajaczkowski, W. & Parsons, C. G. Modulation of learning processes by ionotropic glutamate receptor ligands. Behavioural pharmacology 6, 455–474 (1995).
pubmed: 11224354
Zoladz, P. R. et al. Enhancement of long-term spatial memory in adult rats by the noncompetitive NMDA receptor antagonists, memantine and neramexane. Pharmacology, biochemistry, and behavior 85, 298–306, https://doi.org/10.1016/j.pbb.2006.08.011 (2006).
doi: 10.1016/j.pbb.2006.08.011
pubmed: 17045636
Parsons, C. G., Stoffler, A. & Danysz, W. Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system–too little activation is bad, too much is even worse. Neuropharmacology 53, 699–723, https://doi.org/10.1016/j.neuropharm.2007.07.013 (2007).
doi: 10.1016/j.neuropharm.2007.07.013
pubmed: 17904591
Autry, A. E. et al. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475, 91–95, https://doi.org/10.1038/nature10130 (2011).
doi: 10.1038/nature10130
pubmed: 21677641
pmcid: 3172695
Zheng, W. et al. Neurocognitive performance and repeated-dose intravenous ketamine in major depressive disorder. Journal of affective disorders 246, 241–247, https://doi.org/10.1016/j.jad.2018.12.005 (2019).
doi: 10.1016/j.jad.2018.12.005
pubmed: 30590286
Giuliani, P. et al. Guanine-based purines modulate the effect of L-NAME on learning and memory in rats. Panminerva Med 54, 53–58, doi:R41122762 [pii] (2012).
Vinade, E. R., Izquierdo, I., Lara, D. R., Schmidt, A. P. & Souza, D. O. Oral administration of guanosine impairs inhibitory avoidance performance in rats and mice. Neurobiology of learning and memory 81, 137–143, https://doi.org/10.1016/j.nlm.2003.12.003 , S1074742704000024 [pii] (2004).
Tort, A. B. et al. Guanosine selectively inhibits locomotor stimulation induced by the NMDA antagonist dizocilpine. Behavioural brain research 154, 417–422, https://doi.org/10.1016/j.bbr.2004.03.008 , S0166432804000919 [pii] (2004).
Saute, J. A. et al. Amnesic effect of GMP depends on its conversion to guanosine. Neurobiology of learning and memory 85, 206–212, https://doi.org/10.1016/j.nlm.2005.10.006 (2006).
doi: 10.1016/j.nlm.2005.10.006
pubmed: 16325434
Roesler, R. et al. Guanosine impairs inhibitory avoidance performance in rats. Neuroreport 11, 2537–2540, https://doi.org/10.1097/00001756-200008030-00038 (2000).
doi: 10.1097/00001756-200008030-00038
pubmed: 10943718
Gerbatin, R. R., Dobrachinski, F., Cassol, G., Soares, F. A. A. & Royes, L. F. F. A1 rather than A2A adenosine receptor as a possible target of Guanosine effects on mitochondrial dysfunction following Traumatic Brain Injury in rats. Neuroscience letters 704, 141–144, https://doi.org/10.1016/j.neulet.2019.04.014 (2019).
doi: 10.1016/j.neulet.2019.04.014
pubmed: 30974229
Dobrachinski, F. et al. Guanosine Attenuates Behavioral Deficits After Traumatic Brain Injury by Modulation of Adenosinergic Receptors. Molecular neurobiology 56, 3145–3158, https://doi.org/10.1007/s12035-018-1296-1 (2019).
doi: 10.1007/s12035-018-1296-1
pubmed: 30105669
Almeida, R. F. et al. Guanosine Anxiolytic-Like Effect Involves Adenosinergic and Glutamatergic Neurotransmitter Systems. Molecular neurobiology, https://doi.org/10.1007/s12035-015-9660-x (2016).
Baltaci, S. B., Mogulkoc, R. & Baltaci, A. K. Molecular Mechanisms of Early and Late LTP. Neurochemical research 44, 281–296, https://doi.org/10.1007/s11064-018-2695-4 (2019).
doi: 10.1007/s11064-018-2695-4
pubmed: 30523578
Pereira, G. S. et al. Activation of adenosine receptors in the posterior cingulate cortex impairs memory retrieval in the rat. Neurobiology of learning and memory 83, 217–223, https://doi.org/10.1016/j.nlm.2004.12.002 (2005).
doi: 10.1016/j.nlm.2004.12.002
pubmed: 15820857
Rock, P. L., Roiser, J. P., Riedel, W. J. & Blackwell, A. D. Cognitive impairment in depression: a systematic review and meta-analysis. Psychological medicine 44, 2029–2040, https://doi.org/10.1017/S0033291713002535 (2014).
doi: 10.1017/S0033291713002535
pubmed: 24168753
Hashimoto, K. Rapid-acting Antidepressant Ketamine, Its Metabolites and Other Candidates: A Historical Overview and Future Perspective. Psychiatry and clinical neurosciences, https://doi.org/10.1111/pcn.12902 (2019).
Hoeffer, C. A. & Klann, E. mTOR signaling: at the crossroads of plasticity, memory and disease. Trends in neurosciences 33, 67–75, https://doi.org/10.1016/j.tins.2009.11.003 (2010).
doi: 10.1016/j.tins.2009.11.003
pubmed: 19963289
Su, C. et al. Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis in rats with parkinsonism. Journal of neuroscience research 87, 617–625, https://doi.org/10.1002/jnr.21883 (2009).
doi: 10.1002/jnr.21883
pubmed: 18816792
Rathbone, M., Pilutti, L., Caciagli, F. & Jiang, S. Neurotrophic effects of extracellular guanosine. Nucleosides, nucleotides & nucleic acids 27, 666–672, https://doi.org/10.1080/15257770802143913 (2008).
doi: 10.1080/15257770802143913
Molero, P. et al. Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review. CNS drugs 32, 411–420, https://doi.org/10.1007/s40263-018-0519-3 (2018).
doi: 10.1007/s40263-018-0519-3
pubmed: 29736744
Hendriksen, H., Korte, S. M., Olivier, B. & Oosting, R. S. The olfactory bulbectomy model in mice and rat: one story or two tails? European journal of pharmacology 753, 105–113, https://doi.org/10.1016/j.ejphar.2014.10.033 (2015).
doi: 10.1016/j.ejphar.2014.10.033
pubmed: 25446558
Bansal, Y., Singh, R., Saroj, P., Sodhi, R. K. & Kuhad, A. Naringenin protects against oxido-inflammatory aberrations and altered tryptophan metabolism in olfactory bulbectomized-mice model of depression. Toxicology and applied pharmacology 355, 257–268, https://doi.org/10.1016/j.taap.2018.07.010 (2018).
doi: 10.1016/j.taap.2018.07.010
pubmed: 30017640
Wrynn, A. S. et al. An in-vivo magnetic resonance imaging study of the olfactory bulbectomized rat model of depression. Brain research 879, 193–199, doi:S0006899300026196 [pii] (2000).
Gorwood, P. Neurobiological mechanisms of anhedonia. Dialogues in clinical neuroscience 10, 291–299 (2008).
pubmed: 18979942
pmcid: 3181880
Patel, D., Kas, M. J., Chattarji, S. & Buwalda, B. Rodent models of social stress and neuronal plasticity: Relevance to depressive-like disorders. Behavioural brain research 369, 111900, https://doi.org/10.1016/j.bbr.2019.111900 (2019).
doi: 10.1016/j.bbr.2019.111900
pubmed: 31022420
Antunes, M. S. et al. Hesperidin reverses cognitive and depressive disturbances induced by olfactory bulbectomy in mice by modulating hippocampal neurotrophins and cytokine levels and acetylcholinesterase activity. Eur J Pharmacol 789, 411–420, https://doi.org/10.1016/j.ejphar.2016.07.042 (2016).
doi: 10.1016/j.ejphar.2016.07.042
pubmed: 27460180
Poretti, M. B. et al. Ghrelin effects expression of several genes associated with depression-like behavior. Prog Neuropsychopharmacol Biol Psychiatry 56, 227–234, https://doi.org/10.1016/j.pnpbp.2014.09.012 (2015).
doi: 10.1016/j.pnpbp.2014.09.012
pubmed: 25286107
Holubova, K. et al. Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner. Psychopharmacology 233, 2077–2097, https://doi.org/10.1007/s00213-016-4256-3 (2016).
doi: 10.1007/s00213-016-4256-3
pubmed: 27004790
de Sousa, L. P. et al. Long-term effect of uncomplicated Plasmodium berghei ANKA malaria on memory and anxiety-like behaviour in C57BL/6 mice. Parasites & vectors 11, 191, https://doi.org/10.1186/s13071-018-2778-8 (2018).
doi: 10.1186/s13071-018-2778-8
Leger, M. et al. Object recognition test in mice. Nature protocols 8, 2531–2537, https://doi.org/10.1038/nprot.2013.155 (2013).
doi: 10.1038/nprot.2013.155
pubmed: 24263092