AdipoRon as a Novel Therapeutic Agent for Depression: A Comprehensive Review of Preclinical Evidence
Abstract
1. Introduction
2. Materials and Methods
2.1. Database Search
2.2. Inclusion Criteria
2.3. Exclusion Criteria
2.4. Data Extraction
2.5. Quality Assessment
3. Results
Model Type | Cell Line or Animal | Intervention and AdipoRon Administration | Antidepressant Effects | Pathways | References |
---|---|---|---|---|---|
In vivo experiments Depression-like behavior in STZ + high-fat-diet-induced diabetic rat model | In vivo experiments C57BL/6N mice | In vivo experiments (i.p., injected for two weeks) AdipoRon 20 mg/kg | AdipoRon at a dose of 20 mg/kg significantly improved depression-like behaviors in mice, enhancing sucrose consumption in the sucrose preference test, reducing immobility time in the swimming experiment, and increasing total distance and cross times in movement experiments. | AdipoRon inhibited hippocampal cell apoptosis, increased synapses in the prefrontal cortex and hippocampus, and increased dendritic spine neuronal density in the CA1 region. The molecular pathways included anti-inflammatory effects via NLRP3 inhibition, reduction in ASC and IL-1β levels, increased p-AMPK/AMPK ratio, and decreased p-mTOR/mTOR expression in the treated mouse brains. | [31] |
In vivo experiments 6-OHDA-induced PD rat model | In vivo experiments Wistar rats | In vivo experiments (intranasal, injected for three weeks) AdipoRon 0.1 µg/rat, AdipoRon 1 µg/rat, and AdipoRon 10 µg/rat | AdipoRon at doses of 1 and 10 µg/rat for three consecutive weeks was associated with anxiolytic and antidepressant effects in many behavioral tests, such as the OF, EPM, and forced swimming tests. AdipoRon also lowered corticosterone and inflammasome levels in the treated rats. | AdipoRon mitigated anxious and depressive-like behaviors in the rat model of PD by principally modulating the AMPK/Sirt-1 (↓NLRP3, IL-1β, CAS-1, and ↑Sirt-1) signaling pathway and blocking the NLRP3 inflammasome. | [27] |
In vitro experiments Microglial and hippocampal cells In vivo experiments CUMS | In vitro experiments BV2 and HT22 cells In vivo experiments C57BL/6J mice | In vitro experiments BV2 cells were pretreated with AdipoRon 10, 20, and 40 μM for two hours, and HT22 cells were cultured with the BV2 cell-conditioned medium In vivo experiments (i.p., injected for two weeks) AdipoRon 10 mg/kg, AdipoRon 20 mg/kg, and AdipoRon 40 mg/kg | AdipoRon protected hippocampal neurons cultured with activated microglia, decreased mtROS accumulation, and promoted mitophagy in vitro, which increased the clearance of damaged mitochondria. Additionally, AdipoRon ameliorated depression-like behaviors in vivo. | AdipoRon mitigated NLRP3 inflammasome activation in the microglia by improving mitophagy. | [28] |
In vivo experiments AAV (↑shRNA targeting NMDA subunits Glu2NA and Glu2NB) | In vivo experiments C57BL/6J and CamKIIα-Cre mice | In vivo experiments (i.p., injected for seven days) AdipoRon 20 mg/kg | AdipoRon promoted antidepressant and anxiolytic-like effects even under the knockdown of the NMDA receptor subunits GluN2A and GluN2B in the ventral hippocampus of the treated mice. AdipoRon reduced BDNF levels, long-term potentiation of the perforant path, and neuronal activation in the ventral dentate gyrus. | - | [29] |
In vivo experiments LPS-induced depression-like model | In vivo experiments C57BL/6 APN KO mice | In vivo experiments (i.g, injected for seven days) AdipoRon 50 mg/kg | AdipoRon was found to abolish the antidepressant-like behaviors presented by LPS-treated APN KO mice, increasing immobility and decreasing sucrose preference. However, AdipoRon improved the redox status of the treated mice. | The suggested pathway involved possibly an anti-neuroinflammatory intervention based on the modulation of AdipoRon and BDNF signaling. | [32] |
In vivo experiments CDAD | In vivo experiments C57BL/6J mice | In vivo experiments (i.v. cannulation and i.c.v. injection) AdipoRon 1 µL/1 mM | AdipoRon promoted hippocampal neurogenesis and improved cognitive dysfunction associated with depression. | AdipoRon increased the genetic expression of NICD, ADAM10, Hes1, Hes5, Hey1, and Heyl and upregulated Notch1 signaling. Additionally, it increased the number of Ki67- and DCX-positive cells. AdipoRon may have upregulated the expression of ADAM10 and Notch1 through PPARα and JNK, respectively. | [30] |
In vivo experiments Long-term corticosterone treatment | In vivo experiments C57BL/6J mice | In vivo experiments (i.p., injected for three weeks) AdipoRon 1 mg/kg | AdipoRon positively impacted a depression-like state by blocking corticosterone-induced depression onset. It exerted pleiotropic effects, modulating hippocampal neurogenesis, tryptophan metabolic pathways, neuroinflammation, and serotonergic transmission. AdipoRon mitigated depression-like behaviors. | AdipoRon modulated IL-1β, IL-6, and TNF-α, restored the physiological expression of IDO and KAT in various brain regions, increased the release and turnover of serotonin, and restored physiological levels of critical neurotrophic factors such as BDNF, VEGF-α, IGF-1, and NGF. | [33] |
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Association, A.P. Diagnostic and Statistical Manual of Mental Disorders (DSM-5®); American Psychiatric Publishing: Washington, DC, USA, 2013. [Google Scholar]
- Wallensten, J.; Ljunggren, G.; Nager, A.; Wachtler, C.; Bogdanovic, N.; Petrovic, P.; Carlsson, A.C. Stress, depression, and risk of dementia—A cohort study in the total population between 18 and 65 years old in Region Stockholm. Alzheimers Res. Ther. 2023, 15, 161. [Google Scholar] [CrossRef]
- Zhang, Z.; Jackson, S.L.; Gillespie, C.; Merritt, R.; Yang, Q. Depressive Symptoms and Mortality Among US Adults. JAMA Netw. Open 2023, 6, e2337011. [Google Scholar] [CrossRef] [PubMed]
- Tusa, B.S.; Alati, R.; Ayano, G.; Betts, K.; Weldesenbet, A.B.; Dachew, B. The risk of attention deficit hyperactivity disorder symptoms in offspring of mothers with perinatal depression: A systematic review and meta-analysis. J. Psychiatr. 2024, 102, 104261. [Google Scholar] [CrossRef] [PubMed]
- Chayadi, E.; Baes, N.; Kiropoulos, L. The effects of mindfulness-based interventions on symptoms of depression, anxiety, and cancer-related fatigue in oncology patients: A systematic review and meta-analysis. PLoS ONE 2022, 17, e0269519. [Google Scholar] [CrossRef] [PubMed]
- Geng, H.M.; Chuang, D.M.; Yang, F.; Yang, Y.; Liu, W.M.; Liu, L.H.; Tian, H.M. Prevalence and determinants of depression in caregivers of cancer patients: A systematic review and meta-analysis. Medicine 2018, 97, e11863. [Google Scholar] [CrossRef]
- Cash, E.; Albert, C.; Palmer, I.; Polzin, B.; Kabithe, A.; Crawford, D.; Bumpous, J.M.; Sephton, S.E. Depressive Symptoms, Systemic Inflammation, and Survival Among Patients With Head and Neck Cancer. JAMA Otolaryngol. Head Neck Surg. 2024, 150, 405–413. [Google Scholar] [CrossRef]
- Jalali, A.; Ziapour, A.; Karimi, Z.; Rezaei, M.; Emami, B.; Kalhori, R.P.; Khosravi, F.; Sameni, J.S.; Kazeminia, M. Global prevalence of depression, anxiety, and stress in the elderly population: A systematic review and meta-analysis. BMC Geriatr. 2024, 24, 809. [Google Scholar] [CrossRef]
- Spoelma, M.J.; Sicouri, G.L.; Francis, D.A.; Songco, A.D.; Daniel, E.K.; Hudson, J.L. Estimated Prevalence of Depressive Disorders in Children From 2004 to 2019: A Systematic Review and Meta-Analysis. JAMA Pediatr. 2023, 177, 1017–1027. [Google Scholar] [CrossRef]
- Wang, C.; Tong, Y.; Tang, T.; Wang, X.; Fang, L.; Wen, X.; Su, P.; Wang, J.; Wang, G. Association between adolescent depression and adult suicidal behavior: A systematic review and meta-analysis. Asian J. Psychiatr. 2024, 100, 104185. [Google Scholar] [CrossRef]
- Hu, Y.; Dong, X.; Chen, J. Adiponectin and depression: A meta-analysis. Biomed. Rep. 2015, 3, 38–42. [Google Scholar] [CrossRef]
- Formolo, D.A.; Lee, T.H.; Yau, S.Y. Increasing Adiponergic System Activity as a Potential Treatment for Depressive Disorders. Mol. Neurobiol. 2019, 56, 7966–7976. [Google Scholar] [CrossRef]
- Ng, R.C.; Jian, M.; Ma, O.K.; Xiang, A.W.; Bunting, M.; Kwan, J.S.; Wong, C.W.; Yick, L.W.; Chung, S.K.; Lam, K.S.; et al. Liver-specific adiponectin gene therapy suppresses microglial NLRP3-inflammasome activation for treating Alzheimer’s disease. J. Neuroinflammation 2024, 21, 77. [Google Scholar] [CrossRef]
- Salmons, H.I.; Carstens, M.F.; Limberg, A.K.; Bettencourt, J.W.; Payne, A.N.; Karczewski, D.C.; Ryan, Z.T.; Morrey, M.E.; Sanchez-Sotelo, J.; Berry, D.J.; et al. Efficacy of ADIPOR1 and ADIPOR2 peptide-agonist AdipoRon in preventing contracture in a rabbit model of arthrofibrosis. J. Orthop. Res. 2024, 42, 1916–1922. [Google Scholar] [CrossRef] [PubMed]
- Ohnishi, H.; Zhang, Z.; Yurube, T.; Takeoka, Y.; Kanda, Y.; Tsujimoto, R.; Miyazaki, K.; Matsuo, T.; Ryu, M.; Kumagai, N.; et al. Anti-Inflammatory Effects of Adiponectin Receptor Agonist AdipoRon against Intervertebral Disc Degeneration. Int. J. Mol. Sci. 2023, 24, 8566. [Google Scholar] [CrossRef] [PubMed]
- Tan, W.; Wang, Y.; Cheng, S.; Liu, Z.; Xie, M.; Song, L.; Qiu, Q.; Wang, X.; Li, Z.; Liu, T.; et al. AdipoRon ameliorates the progression of heart failure with preserved ejection fraction via mitigating lipid accumulation and fibrosis. J. Adv. Res. 2024, 68, 299–315. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Chang, Y.; Zhu, J.; Wu, Y.; Jiang, X.; Zheng, S.; Li, G.; Ma, R. AdipoRon mitigates tau pathology and restores mitochondrial dynamics via AMPK-related pathway in a mouse model of Alzheimer’s disease. Exp. Neurol. 2023, 363, 114355. [Google Scholar] [CrossRef]
- Samaha, M.M.; El-Desoky, M.M.; Hisham, F.A. AdipoRon, an adiponectin receptor agonist, modulates AMPK signaling pathway and alleviates ovalbumin-induced airway inflammation in a murine model of asthma. Int. Immunopharmacol. 2024, 136, 112395. [Google Scholar] [CrossRef] [PubMed]
- Barbalho, S.M.; Méndez-Sánchez, N.; Fornari Laurindo, L. AdipoRon and ADP355, adiponectin receptor agonists, in Metabolic-associated Fatty Liver Disease (MAFLD) and Nonalcoholic Steatohepatitis (NASH): A systematic review. Biochem. Pharmacol. 2023, 218, 115871. [Google Scholar] [CrossRef] [PubMed]
- Laurindo, L.F.; Sosin, A.F.; Lamas, C.B.; de Alvares Goulart, R.; Dos Santos Haber, J.F.; Detregiachi, C.R.P.; Barbalho, S.M. Exploring the logic and conducting a comprehensive evaluation of AdipoRon-based adiponectin replacement therapy against hormone-related cancers-a systematic review. Naunyn Schmiedebergs Arch. Pharmacol. 2024, 397, 2067–2082. [Google Scholar] [CrossRef]
- Laurindo, L.F.; Laurindo, L.F.; Rodrigues, V.D.; Catharin, V.; Simili, O.A.G.; Barboza, G.O.; Catharin, V.C.S.; Sloan, K.P.; Barbalho, S.M. Unraveling the rationale and conducting a comprehensive assessment of AdipoRon (adiponectin receptor agonist) as a candidate drug for diabetic nephropathy and cardiomyopathy prevention and intervention-a systematic review. Naunyn Schmiedebergs Arch. Pharmacol. 2024, 398, 165–177. [Google Scholar] [CrossRef]
- Laurindo, L.F.; Laurindo, L.F.; Rodrigues, V.D.; Chagas, E.F.B.; da Silva Camarinha Oliveira, J.; Catharin, V.; Barbalho, S.M. Mechanisms and effects of AdipoRon, an adiponectin receptor agonist, on ovarian granulosa cells-a systematic review. Naunyn Schmiedebergs Arch. Pharmacol. 2024, 398, 1305–1314. [Google Scholar] [CrossRef]
- Fornari Laurindo, L.; Minniti, G.; Dogani Rodrigues, V.; Fornari Laurindo, L.; Cavallari Strozze Catharin, V.M.; Federighi Baisi Chagas, E.; Dias Dos Anjos, V.; Vialogo Marques de Castro, M.; Baldi Júnior, E.; Cristina Ferraroni Sanches, R.; et al. Exploring the Logic and Conducting a Comprehensive Evaluation of the Adiponectin Receptor Agonists AdipoRon and AdipoAI’s Impacts on Bone Metabolism and Repair-A Systematic Review. Curr. Med. Chem. 2024, 32, 1168–1194. [Google Scholar] [CrossRef]
- Barbalho, S.M.; Laurindo, L.F.; de Oliveira Zanuso, B.; da Silva, R.M.S.; Gallerani Caglioni, L.; Nunes Junqueira de Moraes, V.B.F.; Fornari Laurindo, L.; Dogani Rodrigues, V.; da Silva Camarinha Oliveira, J.; Beluce, M.E.; et al. AdipoRon’s Impact on Alzheimer’s Disease-A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2025, 26, 484. [Google Scholar] [CrossRef] [PubMed]
- Morrison, A.; Polisena, J.; Husereau, D.; Moulton, K.; Clark, M.; Fiander, M.; Mierzwinski-Urban, M.; Clifford, T.; Hutton, B.; Rabb, D. The effect of English-language restriction on systematic review-based meta-analyses: A systematic review of empirical studies. Int. J. Technol. Assess. Health Care 2012, 28, 138–144. [Google Scholar] [CrossRef] [PubMed]
- Hooijmans, C.R.; Rovers, M.M.; de Vries, R.B.; Leenaars, M.; Ritskes-Hoitinga, M.; Langendam, M.W. SYRCLE’s risk of bias tool for animal studies. BMC Med. Res. Methodol. 2014, 14, 43. [Google Scholar] [CrossRef] [PubMed]
- Azizifar, N.; Mohaddes, G.; Keyhanmanesh, R.; Athari, S.Z.; Alimohammadi, S.; Farajdokht, F. Intranasal AdipoRon Mitigated Anxiety and Depression-Like Behaviors in 6-OHDA-Induced Parkinson ‘s Disease Rat Model: Going Beyond Motor Symptoms. Neurochem. Res. 2024, 49, 3030–3042. [Google Scholar] [CrossRef]
- Liu, Y.; Fu, X.; Sun, J.; Cui, R.; Yang, W. AdipoRon exerts an antidepressant effect by inhibiting NLRP3 inflammasome activation in microglia via promoting mitophagy. Int. Immunopharmacol. 2024, 141, 113011. [Google Scholar] [CrossRef]
- Formolo, D.A.; Lee, T.H.; Yu, J.; Lin, K.; Chen, G.; Kranz, G.S.; Yau, S.Y. Increasing Adiponectin Signaling by Sub-Chronic AdipoRon Treatment Elicits Antidepressant- and Anxiolytic-Like Effects Independent of Changes in Hippocampal Plasticity. Biomedicines 2023, 11, 249. [Google Scholar] [CrossRef]
- You, J.; Sun, L.; Wang, J.; Sun, F.; Wang, W.; Wang, D.; Fan, X.; Liu, D.; Xu, Z.; Qiu, C.; et al. Role of Adiponectin-Notch pathway in cognitive dysfunction associated with depression and in the therapeutic effect of physical exercise. Aging Cell 2021, 20, e13387. [Google Scholar] [CrossRef]
- Zhao, W.; Li, Y.; Zhou, Y.; Zhao, J.; Lu, Y.; Xu, Z. AdipoRon attenuates depression-like behavior in T2DM mice via inhibiting inflammation and regulating autophagy. Brain Res. Bull. 2025, 224, 111308. [Google Scholar] [CrossRef]
- Li, W.; Ali, T.; Zheng, C.; He, K.; Liu, Z.; Shah, F.A.; Li, N.; Yu, Z.J.; Li, S. Anti-depressive-like behaviors of APN KO mice involve Trkb/BDNF signaling related neuroinflammatory changes. Mol. Psychiatry 2022, 27, 1047–1058. [Google Scholar] [CrossRef]
- Nicolas, S.; Debayle, D.; Béchade, C.; Maroteaux, L.; Gay, A.S.; Bayer, P.; Heurteaux, C.; Guyon, A.; Chabry, J. Adiporon, an adiponectin receptor agonist acts as an antidepressant and metabolic regulator in a mouse model of depression. Transl. Psychiatry 2018, 8, 159. [Google Scholar] [CrossRef] [PubMed]
- Kälviäinen, R. Intranasal therapies for acute seizures. Epilepsy Behav. 2015, 49, 303–306. [Google Scholar] [CrossRef] [PubMed]
- Lunev, E.; Karan, A.; Egorova, T.; Bardina, M. Adeno-Associated Viruses for Modeling Neurological Diseases in Animals: Achievements and Prospects. Biomedicines 2022, 10, 1140. [Google Scholar] [CrossRef] [PubMed]
- Berns, K.I.; Flotte, T.R. Gene Therapy: Use of Viruses as Vectors. In Encyclopedia of Virology, 3rd ed.; Mahy, B.W.J., Van Regenmortel, M.H.V., Eds.; Academic Press: Oxford, UK, 2008; pp. 301–306. [Google Scholar]
- Goins, W.F.; Cohen, J.B.; Glorioso, J.C. Gene therapy for the treatment of chronic peripheral nervous system pain. Neurobiol. Dis. 2012, 48, 255–270. [Google Scholar] [CrossRef]
- Lundstrom, K. Viral Vectors in Gene Therapy: Where Do We Stand in 2023? Viruses 2023, 15, 698. [Google Scholar] [CrossRef]
- Minetti, A. Unlocking the potential of adeno-associated virus in neuroscience: A brief review. Mol. Biol. Rep. 2024, 51, 563. [Google Scholar] [CrossRef]
- Troubat, R.; Barone, P.; Leman, S.; Desmidt, T.; Cressant, A.; Atanasova, B.; Brizard, B.; El Hage, W.; Surget, A.; Belzung, C.; et al. Neuroinflammation and depression: A review. Eur. J. Neurosci. 2021, 53, 151–171. [Google Scholar] [CrossRef]
- Hermanns, H.; Bos, E.M.E.; van Zuylen, M.L.; Hollmann, M.W.; Stevens, M.F. The Options for Neuraxial Drug Administration. CNS Drugs 2022, 36, 877–896. [Google Scholar] [CrossRef]
- Zelek-Molik, A.; Litwa, E. Trends in research on novel antidepressant treatments. Front. Pharmacol. 2025, 16, 1544795. [Google Scholar] [CrossRef]
- Bartova, L.; Fugger, G.; Dold, M.; Kautzky, A.; Fanelli, G.; Zanardi, R.; Albani, D.; Weidenauer, A.; Rujescu, D.; Souery, D.; et al. Real-world characteristics of European patients receiving SNRIs as first-line treatment for major depressive disorder. J. Affect. Disord. 2023, 332, 105–114. [Google Scholar] [CrossRef]
- Marazziti, D.; Mucci, F.; Tripodi, B.; Carbone, M.G.; Muscarella, A.; Falaschi, V.; Baroni, S. Emotional Blunting, Cognitive Impairment, Bone Fractures, and Bleeding as Possible Side Effects of Long-Term Use of SSRIs. Clin. Neuropsychiatry 2019, 16, 75–85. [Google Scholar]
- Chockalingam, R.; Gott, B.M.; Conway, C.R. Tricyclic Antidepressants and Monoamine Oxidase Inhibitors: Are They Too Old for a New Look? Handb. Exp. Pharmacol. 2019, 250, 37–48. [Google Scholar] [CrossRef]
- Edinoff, A.N.; Swinford, C.R.; Odisho, A.S.; Burroughs, C.R.; Stark, C.W.; Raslan, W.A.; Cornett, E.M.; Kaye, A.M.; Kaye, A.D. Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. Health Psychol. Res. 2022, 10, 39576. [Google Scholar] [CrossRef]
- Al Nakhebi, O.A.S.; Albu-Kalinovic, R.; Bosun, A.; Neda-Stepan, O.; Gliga, M.; Crișan, C.A.; Marinescu, I.; Enătescu, V.R. Management of Systemic Cardiotoxicity Associated with Antidepressant Use in Patients with Depressive Disorders: A Systematic Review. J. Clin. Med. 2025, 14, 3696. [Google Scholar] [CrossRef] [PubMed]
- Wang, Z.; Lu, H.; Li, Y.; Huang, S.; Zhang, M.; Wen, Y.; Shang, D. Exploring the correlation between cardiovascular adverse events and antidepressant use: A retrospective pharmacovigilance analysis based on the FDA Adverse Event Reporting System database. J. Affect. Disord. 2024, 367, 96–108. [Google Scholar] [CrossRef]
- Vekhova, K.A.; Namiot, E.D.; Jonsson, J.; Schiöth, H.B. Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clin. Pharmacol. Ther. 2025, 117, 374–386. [Google Scholar] [CrossRef] [PubMed]
- Pardossi, S.; Fagiolini, A.; Cuomo, A. Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Int. J. Mol. Sci. 2024, 25, 13098. [Google Scholar] [CrossRef] [PubMed]
- Vasile, C. CBT and medication in depression (Review). Exp. Ther. Med. 2020, 20, 3513–3516. [Google Scholar] [CrossRef]
- Subramanian, S.; Lopez, R.; Zorumski, C.F.; Cristancho, P. Electroconvulsive therapy in treatment resistant depression. J. Neurol. Sci. 2022, 434, 120095. [Google Scholar] [CrossRef]
- Mollica, A.; Ng, E.; Burke, M.J.; Nestor, S.M.; Lee, H.; Rabin, J.S.; Hamani, C.; Lipsman, N.; Giacobbe, P. Treatment expectations and clinical outcomes following repetitive transcranial magnetic stimulation for treatment-resistant depression. Brain Stimul. 2024, 17, 752–759. [Google Scholar] [CrossRef]
- Zheng, J.; Sun, Z.; Liang, F.; Xu, W.; Lu, J.; Shi, L.; Shao, A.; Yu, J.; Zhang, J. AdipoRon Attenuates Neuroinflammation After Intracerebral Hemorrhage Through AdipoR1-AMPK Pathway. Neuroscience 2019, 412, 116–130. [Google Scholar] [CrossRef]
- Lee, T.H.; Ahadullah; Christie, B.R.; Lin, K.; Siu, P.M.; Zhang, L.; Yuan, T.F.; Komal, P.; Xu, A.; So, K.F.; et al. Chronic AdipoRon Treatment Mimics the Effects of Physical Exercise on Restoring Hippocampal Neuroplasticity in Diabetic Mice. Mol. Neurobiol. 2021, 58, 4666–4681. [Google Scholar] [CrossRef]
- Athari, S.Z.; Keyhanmanesh, R.; Farajdokht, F.; Karimipour, M.; Azizifar, N.; Alimohammadi, S.; Mohaddes, G. AdipoRon improves mitochondrial homeostasis and protects dopaminergic neurons through activation of the AMPK signaling pathway in the 6-OHDA-lesioned rats. Eur. J. Pharmacol. 2024, 985, 177111. [Google Scholar] [CrossRef] [PubMed]
- Song, Y.; Cao, H.; Zuo, C.; Gu, Z.; Huang, Y.; Miao, J.; Fu, Y.; Guo, Y.; Jiang, Y.; Wang, F. Mitochondrial dysfunction: A fatal blow in depression. Biomed. Pharmacother. 2023, 167, 115652. [Google Scholar] [CrossRef] [PubMed]
- Błażejewska, W.; Dąbrowska, J.; Michałowska, J.; Bogdański, P. The Role of Adiponectin and ADIPOQ Variation in Metabolic Syndrome: A Narrative Review. Genes 2025, 16, 699. [Google Scholar] [CrossRef]
- Zatorski, H.; Salaga, M.; Zielińska, M.; Majchrzak, K.; Binienda, A.; Kordek, R.; Małecka-Panas, E.; Fichna, J. AdipoRon, an Orally Active, Synthetic Agonist of AdipoR1 and AdipoR2 Receptors Has Gastroprotective Effect in Experimentally Induced Gastric Ulcers in Mice. Molecules 2021, 26, 2946. [Google Scholar] [CrossRef]
- Ellenbroek, B.; Youn, J. Rodent models in neuroscience research: Is it a rat race? Dis. Model. Mech. 2016, 9, 1079–1087. [Google Scholar] [CrossRef]
- Beauchamp, A.; Yee, Y.; Darwin, B.C.; Raznahan, A.; Mars, R.B.; Lerch, J.P. Whole-brain comparison of rodent and human brains using spatial transcriptomics. Elife 2022, 11, e79418. [Google Scholar] [CrossRef]
- Demetrius, L. Of mice and men. When it comes to studying ageing and the means to slow it down, mice are not just small humans. EMBO Rep. 2005, 6, S39–S44. [Google Scholar] [CrossRef]
- Buch, A.M.; Liston, C. Dissecting diagnostic heterogeneity in depression by integrating neuroimaging and genetics. Neuropsychopharmacology 2021, 46, 156–175. [Google Scholar] [CrossRef]
- Hannon, K.; Easley, T.; Zhang, W.; Lew, D.; Sotiras, A.; Sheline, Y.I.; Marquand, A.; Barch, D.M.; Bijsterbosch, J.D. Parsing Clinical and Neurobiological Sources of Heterogeneity in Depression. Biol. Psychiatry 2025. [Google Scholar] [CrossRef]
- Steffen, A.; Nübel, J.; Jacobi, F.; Bätzing, J.; Holstiege, J. Mental and somatic comorbidity of depression: A comprehensive cross-sectional analysis of 202 diagnosis groups using German nationwide ambulatory claims data. BMC Psychiatry 2020, 20, 142. [Google Scholar] [CrossRef]
- More, S.; Kaleem, M.; Kharwade, R.; Almutairy, A.F.; Shahzad, N.; Ali Mujtaba, M.; Taha, M.; Pise, A.; Zafar, A.; Mahmood, D. Depression unveiled: Insights into etiology and animal models for behavioral assessment, exploring the multifactorial nature and treatment of depression. Brain Res. 2025, 1847, 149313. [Google Scholar] [CrossRef]
- Planchez, B.; Surget, A.; Belzung, C. Animal models of major depression: Drawbacks and challenges. J. Neural Transm. 2019, 126, 1383–1408. [Google Scholar] [CrossRef] [PubMed]
- Becker, M.; Pinhasov, A.; Ornoy, A. Animal Models of Depression: What Can They Teach Us about the Human Disease? Diagnostics 2021, 11, 123. [Google Scholar] [CrossRef] [PubMed]
- Baandrup, L.; Rasmussen, J.Ø.; Mainz, J.; Videbech, P.; Kristensen, S. Patient-reported outcome measures in mental health clinical research: A descriptive review in comparison with clinician-rated outcome measures. Int. J. Qual. Health Care 2022, 34, ii70–ii97. [Google Scholar] [CrossRef] [PubMed]
- Shemesh, Y.; Chen, A. A paradigm shift in translational psychiatry through rodent neuroethology. Mol. Psychiatry 2023, 28, 993–1003. [Google Scholar] [CrossRef]
- Van Norman, G.A. Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach? JACC Basic Transl. Sci. 2019, 4, 845–854. [Google Scholar] [CrossRef]
- Mak, I.W.; Evaniew, N.; Ghert, M. Lost in translation: Animal models and clinical trials in cancer treatment. Am. J. Transl. Res. 2014, 6, 114–118. [Google Scholar]
- Wong, H.H.; Chou, C.Y.C.; Watt, A.J.; Sjöström, P.J. Comparing mouse and human brains. Elife 2023, 12. [Google Scholar] [CrossRef] [PubMed]
- von Mücke-Heim, I.-A.; Urbina-Treviño, L.; Bordes, J.; Ries, C.; Schmidt, M.V.; Deussing, J.M. Introducing a depression-like syndrome for translational neuropsychiatry: A plea for taxonomical validity and improved comparability between humans and mice. Mol. Psychiatry 2023, 28, 329–340. [Google Scholar] [CrossRef] [PubMed]
- Andes, D.; Craig, W.A. Animal model pharmacokinetics and pharmacodynamics: A critical review. Int. J. Antimicrob. Agents 2002, 19, 261–268. [Google Scholar] [CrossRef] [PubMed]
- Dunbar, J.A.; Reddy, P.; Davis-Lameloise, N.; Philpot, B.; Laatikainen, T.; Kilkkinen, A.; Bunker, S.J.; Best, J.D.; Vartiainen, E.; Kai Lo, S.; et al. Depression: An important comorbidity with metabolic syndrome in a general population. Diabetes Care 2008, 31, 2368–2373. [Google Scholar] [CrossRef]
- Ren, Y.; Luo, H.; Jiang, Z.-L. Therapy Management of Metabolic Disorder Comorbidity With Depression. Front. Psychol. 2021, 12, 683320. [Google Scholar] [CrossRef]
- Al-Khatib, Y.; Akhtar, M.A.; Kanawati, M.A.; Mucheke, R.; Mahfouz, M.; Al-Nufoury, M. Depression and Metabolic Syndrome: A Narrative Review. Cureus 2022, 14, e22153. [Google Scholar] [CrossRef]
- Kandi, V.; Vadakedath, S. Clinical Trials and Clinical Research: A Comprehensive Review. Cureus 2023, 15, e35077. [Google Scholar] [CrossRef]
References | D1 | D2 | D3 | D4 | D5 | D6 | D7 | D8 | D9 | D10 | Overall |
---|---|---|---|---|---|---|---|---|---|---|---|
Zhao et al. [31] | |||||||||||
Azizifar et al. [27] | |||||||||||
Liu et al. [28] | |||||||||||
Formolo et al. [29] | |||||||||||
Li et al. [32] | |||||||||||
You et al. [30] | |||||||||||
Nicolas et al. [33] |
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Laurindo, L.F.; Dogani Rodrigues, V.; Haber Mellen, R.; Haber, R.S.d.A.; Valenti, V.E.; Fornari Laurindo, L.; Chagas, E.F.B.; Oliveira, C.M.d.; Direito, R.; Miglino, M.A.; et al. AdipoRon as a Novel Therapeutic Agent for Depression: A Comprehensive Review of Preclinical Evidence. Biomedicines 2025, 13, 1867. https://doi.org/10.3390/biomedicines13081867
Laurindo LF, Dogani Rodrigues V, Haber Mellen R, Haber RSdA, Valenti VE, Fornari Laurindo L, Chagas EFB, Oliveira CMd, Direito R, Miglino MA, et al. AdipoRon as a Novel Therapeutic Agent for Depression: A Comprehensive Review of Preclinical Evidence. Biomedicines. 2025; 13(8):1867. https://doi.org/10.3390/biomedicines13081867
Chicago/Turabian StyleLaurindo, Lucas Fornari, Victória Dogani Rodrigues, Rodrigo Haber Mellen, Rafael Santos de Argollo Haber, Vitor Engrácia Valenti, Lívia Fornari Laurindo, Eduardo Federighi Baisi Chagas, Camila Marcondes de Oliveira, Rosa Direito, Maria Angélica Miglino, and et al. 2025. "AdipoRon as a Novel Therapeutic Agent for Depression: A Comprehensive Review of Preclinical Evidence" Biomedicines 13, no. 8: 1867. https://doi.org/10.3390/biomedicines13081867
APA StyleLaurindo, L. F., Dogani Rodrigues, V., Haber Mellen, R., Haber, R. S. d. A., Valenti, V. E., Fornari Laurindo, L., Chagas, E. F. B., Oliveira, C. M. d., Direito, R., Miglino, M. A., & Barbalho, S. M. (2025). AdipoRon as a Novel Therapeutic Agent for Depression: A Comprehensive Review of Preclinical Evidence. Biomedicines, 13(8), 1867. https://doi.org/10.3390/biomedicines13081867