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PreprintCited by 12Cannabis and Cannabinoid ResearchNeurogenesis and neuroplasticity mechanismsStress Responses and Cortisol

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Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress

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Xapelli, Sara, Rodrigues, Rui, Moreira, João, Vaz, SH, Barateiro, Andreia, Paulo, Sara, Mateus, Joana, Lourenço, Diogo, Ribeiro, Filipa, Loureiro-Campos, Eduardo, Bielefeld, Pascal, Fitzsimons, Carlos, fernandes, Adelaide, Sebastião, Ana, Pinto, Luísa·2023·Translational Psychiatry
DOI 10.21203/rs.3.rs-2855727/v1PMC PMC10981758

Preprint — published as 10.1038/s41398-024-02877-0 · Paper page

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Abstract

Chronic stress is a major risk factor of neuropsychiatric conditions such as depression. Adult hippocampal neurogenesis (AHN) has emerged as a promising target to counteract stress-related disorders given the ability of newborn neurons to facilitate endogenous plasticity. Recent data sheds light on the interaction between cannabinoids and neurotrophic factors underlying the regulation of AHN, with important effects upon cognitive plasticity and emotional flexibility. Since physical exercise (PE) is known to enhance neurotrophin levels, we hypothesized that PE could engage with cannabinoids to influence AHN and that this would result in beneficial effects under stressful conditions. We therefore investigated the actions of modulating cannabinoid type 2 receptors (CB2R), which are devoid of psychotropic effects, in combination with PE in chronically stressed animals. We found that CB2R inhibition, but not CB2R activation, in combination with PE significantly ameliorated stress-evoked emotional changes and cognitive deficits. Importantly, this combined strategy critically shaped stress-induced changes in AHN dynamics, leading to a significant increase in the rates of cell proliferation and differentiation of newborn neurons, and an overall reduction in neuroinflammation. Together, these results show that CB2Rs are crucial regulators of the beneficial effects of PE in countering the effects of chronic stress. Our work emphasizes the importance of understanding the mechanisms behind the actions of cannabinoids and PE and provides a framework for future therapeutic strategies to treat stress-related disorders that capitalize on lifestyle interventions complemented with endocannabinoid pharmacomodulation.

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  1. James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 Diseases and Injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2018;392:1789–1858. · DOI · Paper page
  2. Kraus C, Kadriu B, Lanzenberger R, Zarate CA, Kasper S. Prognosis and improved outcomes in major depression: a review. Translational Psychiatry 2019 9:1. 2019;9:1–17.
  3. Rodrigues RS, Paulo SL, Moreira JB, Tanqueiro SR, Sebastião AM, Diógenes MJ, et al. Adult Neural Stem Cells as Promising Targets in Psychiatric Disorders. Stem Cells Dev. 2020;29:1099–1117. · DOI
  4. Toda T, Parylak SL, Linker SB, Gage FH. The role of adult hippocampal neurogenesis in brain health and disease. Mol Psychiatry. 2019;24:67–87. · DOI · Paper page
  5. Leschik J, Lutz B, Gentile A. Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience? International Journal of Molecular Sciences 2021, Vol 22, Page 7339. 2021;22:7339. · DOI
  6. Boldrini M, Santiago AN, Hen R, Dwork AJ, Rosoklija GB, Tamir H, et al. Hippocampal granule neuron number and dentate gyrus volume in antidepressant-treated and untreated major depression. Neuropsychopharmacology. 2013;38. · DOI · Paper page
  7. Boldrini M, Galfalvy H, Dwork AJ, Rosoklija GB, Trencevska-Ivanovska I, Pavlovski G, et al. Resilience Is Associated With Larger Dentate Gyrus, While Suicide Decedents With Major Depressive Disorder Have Fewer Granule Neurons. Biol Psychiatry. 2019;85:850–862. · DOI · Paper page
  8. Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature. 2011;476:458–461. · DOI · Paper page
  9. Sahay A, Hen R. Adult hippocampal neurogenesis in depression. Nat Neurosci. 2007;10:1110–1115. · DOI · Paper page
  10. Culig L, Surget A, Bourdey M, Khemissi W, le Guisquet AM, Vogel E, et al. Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress. Neuropharmacology. 2017;126:179–189. · DOI
  11. Surget A, Tanti A, Leonardo ED, Laugeray A, Rainer Q, Touma C, et al. Antidepressants recruit new neurons to improve stress response regulation. Mol Psychiatry. 2011;16:1177–1188. · DOI · Paper page
  12. Planchez B, Surget A, Belzung C. Adult hippocampal neurogenesis and antidepressants effects. Curr Opin Pharmacol. 2020;50:88–95. · DOI
  13. Schmidt HD, Duman RS. The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behavioural Pharmacology. 2007;18:391–418. · DOI
  14. Fogaça MV, Galve-Roperh I, Guimarães FS, Campos AC. Cannabinoids, neurogenesis and antidepressant drugs: is there a link? Curr Neuropharmacol. 2013;11:263–275. · DOI
  15. Rodrigues RS, Lourenço DM, Paulo SL, Mateus JM, Ferreira MF, Mouro FM, et al. Cannabinoid Actions on Neural Stem Cells: Implications for Pathophysiology. Molecules. 2019;24:1350. · DOI
  16. Vilar M, Mira H. Regulation of neurogenesis by neurotrophins during adulthood: Expected and unexpected roles. Front Neurosci. 2016;10. · DOI · Paper page
  17. deRoon-Cassini TA, Stollenwerk TM, Beatka M, Hillard CJ. Meet Your Stress Management Professionals: The Endocannabinoids. Trends Mol Med. 2020;26:953–968. · DOI
  18. Gallego-Landin I, García-Baos A, Castro-Zavala A, Valverde O. Reviewing the Role of the Endocannabinoid System in the Pathophysiology of Depression. Front Pharmacol. 2021;12. · DOI
  19. Morena M, Patel S, Bains JS, Hill MN. Neurobiological interactions between stress and the endocannabinoid system. Neuropsychopharmacology. 2016;41:80–102. · DOI
  20. Jiang W, Zhang Y, Xiao L, van Cleemput J, Ji S-P, Bai G, et al. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest. 2005;115:3104–3116. · DOI · Paper page
  21. Ishiguro H, Horiuchi Y, Tabata K, Liu QR, Arinami T, Onaivi ES. Cannabinoid CB2 receptor gene and environmental interaction in the development of psychiatric disorders. Molecules. 2018;23:1–15. · DOI
  22. Stempel AV, Stumpf A, Zhang HY, Özdoğan T, Pannasch U, Theis AK, et al. Cannabinoid Type 2 Receptors Mediate a Cell Type-Specific Plasticity in the Hippocampus. Neuron. 2016;90:795–809. · DOI
  23. Bahi A, al Mansouri S, al Memari E, al Ameri M, Nurulain SM, Ojha S. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiol Behav. 2014;135:119–124. · DOI · Paper page
  24. Zoppi S, Madrigal JL, Caso JR, Garcia-Gutierrez MS, Manzanares J, Leza JC, et al. Regulatory role of the cannabinoid CB2 receptor in stress-induced neuroinflammation in mice. Br J Pharmacol. 2014;171:2814–2826. · DOI
  25. García-Gutiérrez MS, Pérez-Ortiz JM, Gutiérrez-Adán A, Manzanares J. Depression-resistant endophenotype in mice overexpressing cannabinoid CB2 receptors. Br J Pharmacol. 2010;160:1773–1784. · DOI · Paper page
  26. García-Gutiérrez MS, Manzanares J. Overexpression of CB2 cannabinoid receptors decreased vulnerability to anxiety and impaired anxiolytic action of alprazolam in mice. J Psychopharmacol. 2011;25:111–120. · DOI · Paper page
  27. García-Gutiérrez MS, García-Bueno B, Zoppi S, Leza JC, Manzanares J. Chronic blockade of cannabinoid CB2 receptors induces anxiolytic-like actions associated with alterations in GABA(A) receptors. Br J Pharmacol. 2012;165:951–964. · DOI
  28. Onaivi ES, Ishiguro H, Gong JP, Patel S, Meozzi PA, Myers L, et al. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: From mice to human subjects. PLoS One. 2008;3:e1640. · DOI · Paper page
  29. Hillard CJ, Liu Q. Endocannabinoid signaling in the etiology and treatment of major depressive illness. Curr Pharm Des. 2014;20:3795–3811. · DOI
  30. Saraulli D, Costanzi M, Mastrorilli V, Farioli-Vecchioli S. The Long Run: Neuroprotective Effects of Physical Exercise on Adult Neurogenesis from Youth to Old Age. Curr Neuropharmacol. 2017;15:519. · DOI
  31. Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30:464–472. · DOI · Paper page
  32. Castrén E, Võikar V, Rantamäki T. Role of neurotrophic factors in depression. Curr Opin Pharmacol. 2007;7:18–21. · DOI · Paper page
  33. van Praag H. Neurogenesis and Exercise: Past and Future Directions. Neuromolecular Med. 2008;10:128–140. · DOI · Paper page
  34. Wang L, Chang X, She L, Xu D, Huang W, Poo M -m. Autocrine Action of BDNF on Dendrite Development of Adult-Born Hippocampal Neurons. Journal of Neuroscience. 2015;35:8384–8393. · DOI
  35. Choi SH, Li Y, Parada LF, Sisodia SS. Regulation of hippocampal progenitor cell survival, proliferation and dendritic development by BDNF. Mol Neurodegener. 2009;4:52. · DOI
  36. Troubat R, Barone P, Leman S, Desmidt T, Cressant A, Atanasova B, et al. Neuroinflammation and depression: A review. European Journal of Neuroscience. 2021;53:151–171. · DOI · Paper page
  37. Forteza F, Giorgini G, Raymond F. Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome. Cells. 2021;10. · DOI
  38. Charytoniuk T, Zywno H, Konstantynowicz-Nowicka K, Berk K, Bzdega W, Chabowski A. Can physical activity support the endocannabinoid system in the preventive and therapeutic approach to neurological disorders? Int J Mol Sci. 2020;21:1–16. · DOI
  39. Raichlen D a, Foster AD, Seillier A, Giuffrida A, Gerdeman GL. Exercise-induced endocannabinoid signaling is modulated by intensity. Eur J Appl Physiol. 2013;113:869–875. · DOI · Paper page
  40. Wang H, Han J. The endocannabinoid system regulates the moderate exercise-induced enhancement of learning and memory in mice. Journal of Sports Medicine and Physical Fitness. 2020;60:320–328. · DOI
  41. Meyer JD, Crombie KM, Cook DB, Hillard CJ, Koltyn KF. Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder. Med Sci Sports Exerc. 2019;51:1909–1917. · DOI
  42. Marin Bosch B, Bringard A, Logrieco MG, Lauer E, Imobersteg N, Thomas A, et al. A single session of moderate intensity exercise influences memory, endocannabinoids and brain derived neurotrophic factor levels in men. Scientific Reports 2021 11:1. 2021;11:1–14.
  43. Ferreira FF, Ribeiro FF, Rodrigues RS, Sebastião AM, Xapelli S. Brain-derived neurotrophic factor (BDNF) role in cannabinoid-mediated neurogenesis. Front Cell Neurosci. 2018;12:1–16. · DOI
  44. Ribeiro MA, Aguiar RP, Scarante FF, Fusse EJ, W de Oliveira RM, Guimaraes FS, et al. Spontaneous Activity of CB2 Receptors Attenuates Stress-Induced Behavioral and Neuroplastic Deficits in Male Mice. Front Pharmacol. 2022;12. · DOI
  45. Willner P. The chronic mild stress (CMS) model of depression: History, evaluation and usage. Neurobiol Stress. 2017;6:78–93. · DOI · Paper page
  46. Surget A, Saxe M, Leman S, Ibarguen-Vargas Y, Chalon S, Griebel G, et al. Drug-Dependent Requirement of Hippocampal Neurogenesis in a Model of Depression and of Antidepressant Reversal. Biol Psychiatry. 2008;64:293–301. · DOI · Paper page
  47. Monteiro S, Roque S, de Sá-Calçada D, Sousa N, Correia-Neves M, Cerqueira JJ, et al. An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice. Front Psychiatry. 2015;6. · DOI · Paper page
  48. Patki G, Li L, Allam F, Solanki N, Dao AT, Alkadhi K, et al. Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder. Physiol Behav. 2014;130:47–53. · DOI
  49. Lad HV, Liu L, Paya-Cano JL, Parsons MJ, Kember R, Fernandes C, et al. Behavioural battery testing: evaluation and behavioural outcomes in 8 inbred mouse strains. Physiol Behav. 2010;99:301–316. · DOI
  50. Mouro FM, Batalha VL, Ferreira DG, Coelho JE, Baqi Y, Müller CE, et al. Chronic and acute adenosine A2Areceptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1receptor activation. Neuropharmacology. 2017;117:316–327. · DOI
  51. Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmacol. 1977;47:379–391. · DOI · Paper page
  52. Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007;2:322–328. · DOI · Paper page
  53. Hoffman KL. What can animal models tell us about depressive disorders? Modeling Neuropsychiatric Disorders in Laboratory Animals, Woodhead Publishing; 2016. p. 35–86. · DOI
  54. Ferreiro E, Lanzillo M, Canhoto D, Carvalho da Silva AM, Mota SI, Dias IS, et al. Chronic hyperglycemia impairs hippocampal neurogenesis and memory in an Alzheimer’s disease mouse model. Neurobiol Aging. 2020;92:98–113. · DOI
  55. Alves ND, Patrício P, Correia JS, Mateus-Pinheiro A, Machado-Santos AR, Loureiro-Campos E, et al. Chronic stress targets adult neurogenesis preferentially in the suprapyramidal blade of the rat dorsal dentate gyrus. Brain Struct Funct. 2018;223:415–428. · DOI
  56. Tanti A, Belzung C. Neurogenesis along the septo-temporal axis of the hippocampus: are depression and the action of antidepressants region-specific? Neuroscience. 2013;252:234–252. · DOI
  57. Hawley DF, Leasure JL. Region-specific response of the hippocampus to chronic unpredictable stress. Hippocampus. 2012;22:1338–1349. · DOI
  58. Ribeiro FF, Ferreira F, Rodrigues RS, Soares R, Pedro DM, Duarte-Samartinho M, et al. Regulation of hippocampal postnatal and adult neurogenesis by adenosine A2A receptor: Interaction with brain-derived neurotrophic factor. Stem Cells. 2021;39:1362–1381. · DOI
  59. van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999;96:13427–13431. · DOI · Paper page
  60. Gubert C, Hannan AJ. Exercise mimetics: harnessing the therapeutic effects of physical activity. Nat Rev Drug Discov. 2021;20:862–879. · DOI
  61. Sohroforouzani AM, Shakerian S, Ghanbarzadeh M, Alaei H. Effect of forced treadmill exercise on stimulation of BDNF expression, depression symptoms, tactile memory and working memory in LPS-treated rats. Behavioural Brain Research. 2022;418. · DOI
  62. Hillard CJ. Circulating Endocannabinoids: From Whence Do They Come and Where are They Going? Neuropsychopharmacology. 2018;43:155–172. · DOI
  63. Hill MN, Patel S, Campolongo P, Tasker JG, Wotjak CT, Bains JS. Functional interactions between stress and the endocannabinoid system: from synaptic signaling to behavioral output. J Neurosci. 2010;30:14980–14986. · DOI · Paper page
  64. Heyman E, Gamelin FX, Goekint M, Piscitelli F, Roelands B, Leclair E, et al. Intense exercise increases circulating endocannabinoid and BDNF levels in humans-Possible implications for reward and depression. Psychoneuroendocrinology. 2012;37:844–851. · DOI · Paper page
  65. Hill MN, Titterness AK, Morrish AC, Carrier EJ, Lee TT-Y, Gil-mohapel J, et al. Endogenous cannabinoid signaling is required for voluntary exercise-induced enhancement of progenitor cell proliferation in the hippocampus. Hippocampus. 2010;523:513–523. · DOI
  66. Burstein O, Shoshan N, Doron R, Akirav I. Cannabinoids prevent depressive-like symptoms and alterations in BDNF expression in a rat model of PTSD. Prog Neuropsychopharmacol Biol Psychiatry. 2018;84:129–139. · DOI
  67. Aso E, Juvés S, Maldonado R, Ferrer I. CB2 Cannabinoid Receptor Agonist Ameliorates Alzheimer-Like Phenotype in AβPP/PS1 Mice. Journal of Alzheimer’s Disease. 2013;35:847–858. · DOI
  68. Nollet M, Gaillard P, Tanti A, Girault V, Belzung C, Leman S. Neurogenesis-independent antidepressant-like effects on behavior and stress axis response of a dual orexin receptor antagonist in a rodent model of depression. Neuropsychopharmacology. 2012;37:2210–2221. · DOI
  69. Jayatissa MN, Bisgaard C, Tingström A, Papp M, Wiborg O. Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression. Neuropsychopharmacology. 2006;31:2395–2404. · DOI
  70. Tanti A, Rainer Q, Minier F, Surget A, Belzung C. Differential environmental regulation of neurogenesis along the septo-temporal axis of the hippocampus. Neuropharmacology. 2012;63:374–384. · DOI
  71. Nishijima T, Kawakami M, Kita I. Long-Term Exercise Is a Potent Trigger for ∆FosB Induction in the Hippocampus along the dorso–ventral Axis. PLoS One. 2013;8:e81245. · DOI
  72. Castilla-Ortega E, Rosell-Valle C, Pedraza C, Rodríguez de Fonseca F, Estivill-Torrús G, Santín LJ. Voluntary exercise followed by chronic stress strikingly increases mature adult-born hippocampal neurons and prevents stress-induced deficits in ‘what-when-where’ memory. Neurobiol Learn Mem. 2014;109:62–73. · DOI · Paper page
  73. Snyder JS, Glover LR, Sanzone KM, Kamhi JF, Cameron H a. The effects of exercise and stress on the survival and maturation of adult-generated granule cells. Hippocampus. 2009;19:898–906.
  74. Mensching L, Djogo N, Keller C, Rading S, Karsak M. Stable adult hippocampal neurogenesis in cannabinoid receptor CB2 deficient mice. Int J Mol Sci. 2019;20. · DOI
  75. Berdugo-Vega G, Lee CC, Garthe A, Kempermann G, Calegari F. Adult-born neurons promote cognitive flexibility by improving memory precision and indexing. Hippocampus. 2021;31:1068–1079. · DOI
  76. Wu M v., Sahay A, Duman RS, Hen R. Functional differentiation of adult-born neurons along the septotemporal axis of the dentate gyrus. Cold Spring Harb Perspect Biol. 2015;7.
  77. Tuncdemir SN, Lacefield CO, Hen R. Contributions of adult neurogenesis to dentate gyrus network activity and computations. Behavioural Brain Research. 2019;374. · DOI
  78. Heine VM, Maslam S, Zareno J, Joëls M, Lucassen PJ. Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible. European Journal of Neuroscience. 2004;19:131–144. · DOI · Paper page
  79. Schoenfeld TJ, Rada P, Pieruzzini PR, Hsueh B, Gould E. Physical Exercise Prevents Stress-Induced Activation of Granule Neurons and Enhances Local Inhibitory Mechanisms in the Dentate Gyrus. Journal of Neuroscience. 2013;33:7770–7777. · DOI · Paper page
  80. Sun D, Milibari L, Pan JX, Ren X, Yao LL, Zhao Y, et al. Critical Roles of Embryonic Born Dorsal Dentate Granule Neurons for Activity-Dependent Increases in BDNF, Adult Hippocampal Neurogenesis, and Antianxiety-like Behaviors. Biol Psychiatry. 2021;89:600–614. · DOI
  81. Mograbi KDM, Suchecki D, da Silva SG, Covolan L, Hamani C. Chronic unpredictable restraint stress increases hippocampal pro-inflammatory cytokines and decreases motivated behavior in rats. Stress. 2020;23:427–436. · DOI
  82. Kreisel T, Frank MG, Licht T, Reshef R, Ben-Menachem-Zidon O, Baratta M v., et al. Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis. Mol Psychiatry. 2014;19:699–709. · DOI · Paper page
  83. Mee-inta O, Zhao Z-W, Kuo Y-M. Physical Exercise Inhibits Inflammation and Microglial Activation. Cells 2019, Vol 8, Page 691. 2019;8:691.
  84. dos Santos RS, Sorgi CA, Peti APF, Veras FP, Faccioli LH, Galdino G. Involvement of Spinal Cannabinoid CB 2 Receptors in Exercise-Induced Antinociception. Neuroscience. 2019;418:177–188. · DOI
  85. Komorowska-Müller JA, Schmöle AC. CB2 receptor in microglia: The guardian of self-control. Int J Mol Sci. 2021;22:1–27.
  86. Valencia-Sanchez S, Nava-Castro KE, Palacios-Arreola MI, Prospero-Garcia O, Morales-Montor J, Drucker-Colin R. Chronic exercise modulates the cellular immunity and its cannabinoid receptors expression. PLoS One. 2019;14:e0220542. · DOI
  87. Anacker C, Luna VM, Stevens GS, Millette A, Shores R, Jimenez JC, et al. Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature. 2018;559:98–102. · DOI · Paper page
  88. Bolognini D, Cascio MG, Parolaro D, Pertwee RG. AM630 behaves as a protean ligand at the human cannabinoid CB2 receptor. Br J Pharmacol. 2012;165:2561. · DOI
  89. Kenakin T. Inverse, protean, and ligand-selective agonism: matters of receptor conformation. FASEB J. 2001;15:598–611. · DOI

Metadata

Authors
Xapelli, S., Rodrigues, R., Moreira, J., Vaz, S., Barateiro, A., Paulo, S., Mateus, J., Lourenço, D., Ribeiro, F., Loureiro-Campos, E., Bielefeld, P., Fitzsimons, C., fernandes, A., Sebastião, A., & Pinto, L.
Affiliations
  • University of Lisbon (PT)
  • University of Amsterdam (NL)
  • University of Minho (PT)
Corresponding author
Xapelli, Sara
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2023-06-17
Volume
14
Issue
1
Pages
170-170
ISSN
2158-3188 (ISSN-L)
DOI
10.21203/rs.3.rs-2855727/v1
PMC
PMC10981758
OpenAlex
W4393334203
Cited by
12
References
1
Citations by year
2026: 4 · 2025: 7 · 2024: 1
FWCI
3.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • UvA-DARE (University of Amsterdam) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Funders
  • European Commission (H2020-WIDESPREAD-05-2020-Twinning (EpiEpinet, 2020 ‘, 952455, HORIZON2020, H2020)
  • International Brain Research Organization
  • International Society for Neurochemistry
  • Horizon 2020 Framework Programme (952455)
  • Fundação para a Ciência e a Tecnologia (2020.04492.BD, PTDC/MED-PAT/2582/2021, UIDB/04138/2020; UIDP/04138/ 2020, 04138, PD/BD/150341/2019, 2022.02201.PTDC, UIDB/04138, IF/01227/2015, COVID/BD/151880/2021, H2020, PD/BD/141784/2018, SFRH/BD/129710/2017, PD/BD/150343/2019, /2017, 2020.02855.CEECIND, 952455, UIDB/04138/2020, 2020.04492, UIDP/04138/2020)
  • Erasmus+
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
cannabinoid type 2 receptor, physical activity, chronic stress, adult hippocampal neurogenesis, depression, brain-derived neurotrophic factor, neuroinflammation, neurotrophic factors, stress-related disorders, cognitive impairment, emotional flexibility
MeSH terms
Animals, Antidepressive Agents, Cannabinoids, Hippocampus, Exercise, Receptors, Cannabinoid, Neurogenesis

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