Sex-Related and Brain Regional Differences of URB597 Effects on Modulation of MAPK/PI3K Signaling in Chronically Stressed Rats.

Depression Endocannabinoids IL-1β MAPK/PI3K signaling NLRP3 Sex differences

Journal

Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963

Informations de publication

Date de publication:
19 Sep 2023
Historique:
received: 21 02 2023
accepted: 08 09 2023
medline: 19 9 2023
pubmed: 19 9 2023
entrez: 19 9 2023
Statut: aheadofprint

Résumé

Gender differences exist in depression incidence and antidepressant efficacy. In addition to the neurotransmission theory of depression, inflammation and disrupted signaling pathways play crucial roles in the pathophysiology of depression. Endocannabinoids offer a novel approach to treat inflammatory and emotional disorders like depression. URB597, a FAAH inhibitor, reduces endocannabinoids breakdown. In this study, URB597 effects were investigated on the pro-inflammatory cytokine interleukin-1β (IL-1β), nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3), and mitogen-activated protein kinase (MAPK)/ phosphatidylinositol 3-hydroxy kinase/ protein kinase B (PI3K) signaling in the hippocampus and the medial prefrontal cortex (mPFC) of male and female rats subjected to chronic unpredictable stress (CUS). The results show that CUS induces depression-like behaviors, and the URB597 exhibited antidepressant-like effects inboth sexes. URB597 reduced the CUS-induced NLRP3 and IL-1β increase in the hippocampus and mPFC of both sexes. URB597 increased the reduced pERK1/2 levels in the mPFC of both sexes and hippocampus of CUS males. URB597 also prevented the increase in p38 phosphorylation after chronic stress in the mPFC of both sexes and in the hippocampus of the females. The CUS suppressed the downstream Akt phosphorylation in the mPFC and hippocampi of both sexes. URB597 produced an up-regulation of the pAkt in the hippocampus of the CUS animals but did not affect the pAkt in the mPFC. These data demonstrated a sexual dimorphism in the neural cell signaling, and in the effects of endocannabinoids, and indicated these dimorphisms are region-specific.

Identifiants

DOI: 10.1007/s12035-023-03649-5 PMID: 37725215
pubmed: 37725215
doi: 10.1007/s12035-023-03649-5
pii: 10.1007/s12035-023-03649-5
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja
ID : 451-03-47/2023-01/200017

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Références

Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE et al (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey replication (NCS-R). JAMA 289(23):3095–3105
pubmed: 12813115 doi: 10.1001/jama.289.23.3095
Kokras N, Dalla C (2017) Preclinical sex differences in depression and antidepressant response: implications for clinical research. J Neurosci Res 95(1–2):731–736
pubmed: 27870451 doi: 10.1002/jnr.23861
Sramek JJ, Murphy MF, Cutler NR (2022) Sex differences in the psychopharmacological treatment of depression. Dialogues Clin Neurosci 18(4):447-457
Pitychoutis M, Zisaki P, Dalla A, Papadopoulou-Daifoti C (2010) Pharmacogenetic insights into depression and antidepressant response: does sex matter? Curr Pharm Des 16(20):2214–2223
pubmed: 20459391 doi: 10.2174/138161210791792831
Price RB, Duman R (2020) Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model. Mol Psychiatry 25(3):530–543
pubmed: 31801966 doi: 10.1038/s41380-019-0615-x
Grygiel-Górniak B, Limphaibool N, Puszczewicz M (2019) Cytokine secretion and the risk of depression development in patients with connective tissue diseases. J Neuropsychiatry Clin Neurosci 73(6):302–316
Pan Y, Chen X-Y, Zhang Q-Y, Kong L-D (2014) Microglial NLRP3 inflammasome activation mediates IL-1β-related inflammation in prefrontal cortex of depressive rats. Brain Behav Immun 41:90–100
pubmed: 24859041 doi: 10.1016/j.bbi.2014.04.007
Kaufmann FN, Costa AP, Ghisleni G, Diaz AP, Rodrigues ALS, Peluffo H, Kaster MP (2017) NLRP3 inflammasome-driven pathways in depression: clinical and preclinical findings. Brain Behav Immun 64:367–383
pubmed: 28263786 doi: 10.1016/j.bbi.2017.03.002
Xue J, Li H, Deng X, Ma Z, Fu Q, Ma S (2015) L-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters. Pharmacol Biochem Behav 134:42–48
pubmed: 25937574 doi: 10.1016/j.pbb.2015.04.014
Wang JQ, Mao L (2019) The ERK pathway: molecular mechanisms and treatment of depression. Mol Neurobiol 56:6197–6205
pubmed: 30737641 pmcid: 6684449 doi: 10.1007/s12035-019-1524-3
Kim EK, Choi E-J (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta (BBA)-Mol Basis Dis 1802(4):396–405
doi: 10.1016/j.bbadis.2009.12.009
Li Y-H, Fu H-L, Tian M-L, Wang Y-Q, Chen W, Cai L-L, Zhou X-H, Yuan H-B (2016) Neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-κB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice. Sci Rep 6(1):19869
pubmed: 26813160 pmcid: 4728497 doi: 10.1038/srep19869
Peltier J, O’Neill A, Schaffer DV (2007) PI3K/Akt and CREB regulate adult neural hippocampal progenitor proliferation and differentiation. Dev Neurobiol 67(10):1348–1361
pubmed: 17638387 doi: 10.1002/dneu.20506
Ives A, Nomura J, Martinon F, Roger T, LeRoy D, Miner JN, Simon G, Busso N et al (2015) Xanthine oxidoreductase regulates macrophage IL1β secretion upon NLRP3 inflammasome activation. Nat Commun 6(1):6555
pubmed: 25800347 doi: 10.1038/ncomms7555
Kitagishi Y, Kobayashi M, Kikuta K, Matsuda S (2012) Roles of PI3K/AKT/GSK3/mTOR pathway in cell signaling of mental illnesses. Depress Res Treat 2012:752563
Losenkov IS, Vyalova NM, Simutkin GG, Bokhan NA, Ivanova SA (2016) An association of AKT1 gene polymorphism with antidepressant treatment response. World J Biol Psychiatry 17(3):239–242
pubmed: 26515520 doi: 10.3109/15622975.2015.1112921
Silveira KM, Wegener G, Joca SR (2021) Targeting 2-arachidonoylglycerol signalling in the neurobiology and treatment of depression. Basic Clin Pharmacol Toxicol 129(1):3–14
pubmed: 33905617 doi: 10.1111/bcpt.13595
Fowler CJ (2015) The potential of inhibitors of endocannabinoid metabolism as anxiolytic and antidepressive drugs—A practical view. Eur Neuropsychopharmacol 25(6):749–762
pubmed: 25791296 doi: 10.1016/j.euroneuro.2015.02.005
Morris G, Walder K, Kloiber S, Amminger P, Berk M, Bortolasci CC, Maes M, Puri BK et al (2021) The endocannabinoidome in neuropsychiatry: Opportunities and potential risks. Pharmacol Res 170:105729
pubmed: 34119623 doi: 10.1016/j.phrs.2021.105729
Worley NB, Hill MN, Christianson JP (2018) Prefrontal endocannabinoids, stress controllability and resilience: a hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 85:180–188
pubmed: 28392485 doi: 10.1016/j.pnpbp.2017.04.004
Segev A, Korem N, Mizrachi Zer-Aviv T, Abush H, Lange R, Sauber G, Hillard CJ, Akirav I (2018) Role of endocannabinoids in the hippocampus and amygdala in emotional memory and plasticity. Neuropsychopharmacology 43(10):2017–2027
pubmed: 29977073 pmcid: 6098035 doi: 10.1038/s41386-018-0135-4
Piomelli D, Tarzia G, Duranti A, Tontini A, Mor M, Compton TR, Dasse O, Monaghan EP et al (2006) Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Rev 12(1):21–38
pubmed: 16834756 pmcid: 6741741 doi: 10.1111/j.1527-3458.2006.00021.x
Alteba S, Zer-Aviv TM, Tenenhaus A, David GB, Adelman J, Hillard CJ, Doron R, Akirav I (2020) Antidepressant-like effects of URB597 and JZL184 in male and female rats exposed to early life stress. Eur Neuropsychopharmacol 39:70–86
pubmed: 32891517 doi: 10.1016/j.euroneuro.2020.08.005
Jankovic M, Spasojevic N, Ferizovic H, Stefanovic B, Dronjak S (2020) Inhibition of the fatty acid amide hydrolase changes behaviors and brain catecholamines in a sex-specific manner in rats exposed to chronic unpredictable stress. Physiol Behav 227:113174
pubmed: 32966816 doi: 10.1016/j.physbeh.2020.113174
Jankovic M, Spasojevic N, Ferizovic H, Stefanovic B, Dronjak S (2022) Sex specific effects of the fatty acid amide hydrolase inhibitor URB597 on memory and brain β2-adrenergic and D1-dopamine receptors. Neurosci Lett 768:136363
pubmed: 34843876 doi: 10.1016/j.neulet.2021.136363
Bortolato M, Mangieri RA, Fu J, Kim JH, Arguello O, Duranti A, Tontini A, Mor M et al (2007) Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress. Biol Psychiatry 62(10):1103–1110
pubmed: 17511970 doi: 10.1016/j.biopsych.2006.12.001
Papp M (2012) Models of affective illness: chronic mild stress in the rat. Curr Protocols Pharmacol 57(1):5 (1-5.9. 11)
doi: 10.1002/0471141755.ph0509s57
Willner P, Muscat R, Papp M (1992) Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehavioral Reviews 16(4):525–534
doi: 10.1016/S0149-7634(05)80194-0
Dalla C, Pitychoutis PM, Kokras N, Papadopoulou-Daifoti Z (2011) Sex differences in response to stress and expression of depressive-like behaviours in the rat. Biological basis of sex differences in psychopharmacology, 97–118
Karisetty BC, Joshi PC, Kumar A, Chakravarty S (2017) Sex differences in the effect of chronic mild stress on mouse prefrontal cortical BDNF levels: a role of major ovarian hormones. Neuroscience 356:89–101
pubmed: 28527954 doi: 10.1016/j.neuroscience.2017.05.020
Xing Y, He J, Hou J, Lin F, Tian J, Kurihara H (2013) Gender differences in CMS and the effects of antidepressant venlafaxine in rats. Neurochem Int 63(6):570–575
pubmed: 24090637 doi: 10.1016/j.neuint.2013.09.019
Feng X, Zhao Y, Yang T, Song M, Wang C, Yao Y, Fan H (2019) Glucocorticoid-driven NLRP3 inflammasome activation in hippocampal microglia mediates chronic stress-induced depressive-like behaviors. Front Mol Neurosci 12:210
pubmed: 31555091 pmcid: 6727781 doi: 10.3389/fnmol.2019.00210
Jo E-K, Kim JK, Shin D-M, Sasakawa C (2016) Molecular mechanisms regulating NLRP3 inflammasome activation. Cell Mol Immunol 13(2):148–159
pubmed: 26549800 doi: 10.1038/cmi.2015.95
Su W-J, Zhang Y, Chen Y, Gong H, Lian Y-J, Peng W, Liu Y-Z, Wang Y-X et al (2017) NLRP3 gene knockout blocks NF-κB and MAPK signaling pathway in CUMS-induced depression mouse model. Behav Brain Res 322:1–8
pubmed: 28093255 doi: 10.1016/j.bbr.2017.01.018
Iwata M, Ota KT, Duman RS (2013) The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav Immun 31:105–114
pubmed: 23261775 doi: 10.1016/j.bbi.2012.12.008
Mikkelsen K, Stojanovska L, Prakash M, Apostolopoulos V (2017) The effects of vitamin B on the immune/cytokine network and their involvement in depression. Maturitas 96:58–71
pubmed: 28041597 doi: 10.1016/j.maturitas.2016.11.012
Li B, Chen M, Guo L, Yun Y, Li G, Sang N (2017) Endocannabinoid 2-arachidonoylglycerol protects inflammatory insults from sulfur dioxide inhalation via cannabinoid receptors in the brain. J Environ Sci 51:265–274
doi: 10.1016/j.jes.2016.05.031
Gong W, Zhang S, Zong Y, Halim M, Ren Z, Wang Y, Ma Y, Li B, Ma L, Zhou G (2019) Involvement of the microglial NLRP3 inflammasome in the anti-inflammatory effect of the antidepressant clomipramine. J Affect Disord 254:15–25
pubmed: 31082627 doi: 10.1016/j.jad.2019.05.009
Park H-J, Shim H-S, An K, Starkweather A, Kim KS, Shim I (2015) IL-4 inhibits IL-1β-induced depressive-like behavior and central neurotransmitter alterations. Mediators Inflamm 2015:941413
Benito C, Núñez E, Tolón RM, Carrier EJ, Rábano A, Hillard CJ, Romero J (2003) Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains. J Neurosci 23(35):11136–11141
pubmed: 14657172 pmcid: 6741043 doi: 10.1523/JNEUROSCI.23-35-11136.2003
Qi X, Lin W, Li J, Pan Y, Wang W (2006) The depressive-like behaviors are correlated with decreased phosphorylation of mitogen-activated protein kinases in rat brain following chronic forced swim stress. Behav Brain Res 175(2):233–240
pubmed: 17050000 doi: 10.1016/j.bbr.2006.08.035
Iio W, Matsukawa N, Tsukahara T, Kohari D, Toyoda A (2011) Effects of chronic social defeat stress on MAP kinase cascade. Neurosci Lett 504(3):281–284
pubmed: 21970968 doi: 10.1016/j.neulet.2011.09.047
Yoon D-H, Yoon S, Kim D, Kim H, Baik J-H (2015) Regulation of dopamine D2 receptor-mediated extracellular signal-regulated kinase signaling and spine formation by GABAA receptors in hippocampal neurons. Neurosci Lett 586:24–30
pubmed: 25483619 doi: 10.1016/j.neulet.2014.12.010
Haroon E, Raison CL, Miller AH (2012) Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology 37(1):137–162
pubmed: 21918508 doi: 10.1038/npp.2011.205
Zhu C-B, Lindler KM, Owens AW, Daws LC, Blakely RD, Hewlett WA (2010) Interleukin-1 receptor activation by systemic lipopolysaccharide induces behavioral despair linked to MAPK regulation of CNS serotonin transporters. Neuropsychopharmacology 35(13):2510–2520
pubmed: 20827273 pmcid: 3055584 doi: 10.1038/npp.2010.116
Martín-Hernández D, Caso JR, Javier Meana J, Callado LF, Madrigal JL, García-Bueno B, Leza JC (2018) Intracellular inflammatory and antioxidant pathways in postmortem frontal cortex of subjects with major depression: effect of antidepressants. J Neuroinflamm 15:1–12
doi: 10.1186/s12974-018-1294-2
Xu B, Lian S, Guo J-R, Wang J-F, Zhang L-P, Li S-Z, Yang H-M (2019) Activation of the MAPK signaling pathway induces upregulation of pro-apoptotic proteins in the hippocampi of cold stressed adolescent mice. Neurosci Lett 699:97–102
pubmed: 30711527 doi: 10.1016/j.neulet.2018.12.028
Mitic M, Lukic I, Bozovic N, Djordjevic J, Adzic M (2015) Fluoxetine signature on hippocampal MAPK signalling in sex-dependent manner. J Mol Neurosci 55:335–346
pubmed: 24841087 doi: 10.1007/s12031-014-0328-1
García-Fuster M, Díez-Alarcia R, Ferrer-Alcón M, La Harpe R, Meana J, García-Sevilla J (2014) FADD adaptor and PEA-15/ERK1/2 partners in major depression and schizophrenia postmortem brains: basal contents and effects of psychotropic treatments. Neuroscience 277:541–551
pubmed: 25075716 doi: 10.1016/j.neuroscience.2014.07.027
Wang S, Zhang H, Geng B, Xie Q, Li W, Deng Y, Shi W, Pan Y, Kang X, Wang J (2018) 2-arachidonyl glycerol modulates astrocytic glutamine synthetase via p38 and ERK1/2 pathways. J Neuroinflamm 15(1):1–10
doi: 10.1186/s12974-018-1254-x
Yu JS, Cui W (2016) Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development 143(17):3050–3060
pubmed: 27578176 doi: 10.1242/dev.137075
Mundi PS, Sachdev J, McCourt C, Kalinsky K (2016) AKT in cancer: new molecular insights and advances in drug development. Br J Clin Pharmacol 82(4):943–956
pubmed: 27232857 pmcid: 5137819 doi: 10.1111/bcp.13021
Zeni ALB, Zomkowski ADE, Maraschin M, Rodrigues ALS, Tasca CI (2012) Involvement of PKA, CaMKII, PKC, MAPK/ERK and PI3K in the acute antidepressant-like effect of ferulic acid in the tail suspension test. Pharmacol Biochem Behav 103(2):181–186
pubmed: 22960128 doi: 10.1016/j.pbb.2012.08.020
Cunha MP, Budni J, Ludka FK, Pazini FL, Rosa JM, Oliveira Á, Lopes MW, Tasca CI et al (2016) Involvement of PI3K/Akt signaling pathway and its downstream intracellular targets in the antidepressant-like effect of creatine. Mol Neurobiol 53:2954–2968
pubmed: 25943184 doi: 10.1007/s12035-015-9192-4
Li T, Liu H, Wang X, Xie Y, Bai X, Wu L, Wang Z, Liu D (2016) Resveratrol exerts antidepressant properties in the chronic unpredictable mild stress model through the regulation of oxidative stress and mTOR pathway in the rat hippocampus and prefrontal cortex. Behav Brain Res 302:191–199
pubmed: 26801825 doi: 10.1016/j.bbr.2016.01.037
Palumbo S, Paterson C, Yang F, Hood VL, Law AJ (2021) PKBβ/AKT2 deficiency impacts brain mTOR signaling, prefrontal cortical physiology, hippocampal plasticity and select murine behaviors. Mol Psychiatry 26(2):411–428
pubmed: 33328589 doi: 10.1038/s41380-020-00964-4

Auteurs

Milica Jankovic (M)

Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", National Institute of thе Republic of Serbia, University of Belgrade, P.O.B. 522 - 090, 11000, Belgrade, Serbia.

Natasa Spasojevic (N)

Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", National Institute of thе Republic of Serbia, University of Belgrade, P.O.B. 522 - 090, 11000, Belgrade, Serbia.

Harisa Ferizovic (H)

Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", National Institute of thе Republic of Serbia, University of Belgrade, P.O.B. 522 - 090, 11000, Belgrade, Serbia.

Bojana Stefanovic (B)

Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", National Institute of thе Republic of Serbia, University of Belgrade, P.O.B. 522 - 090, 11000, Belgrade, Serbia.

Kristina Virijevic (K)

Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", National Institute of thе Republic of Serbia, University of Belgrade, P.O.B. 522 - 090, 11000, Belgrade, Serbia.

Milica Vezmar (M)

Institute of Mental Health, University of Belgrade, Belgrade, Serbia.

Sladjana Dronjak (S)

Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", National Institute of thе Republic of Serbia, University of Belgrade, P.O.B. 522 - 090, 11000, Belgrade, Serbia. sladj@vinca.rs.
ORCID: 0000-0002-4334-8002

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