An overview of the molecular and physiological antidepressant mechanisms of physical exercise in animal models of depression

Oliveira, Lucas Renan Sena de; Machado, Frederico Sander Mansur; Rocha-Dias, Isabella; Magalhães, Caíque Olegário Diniz e; Sousa, Ricardo Augusto Leoni De; Cassilhas, Ricardo Cardoso

doi:10.1007/s11033-022-07156-z

Cited by 13 publications

(4 citation statements)

References 107 publications

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“…4d) indicative of antidepressive-like and/or increased coping behaviour (Lucki, 1997). Our findings of exercise exerting antidepressant-like effects are in line with pre-clinical (Steyn et al, 2020;Gruhn et al, 2021;de Oliveira et al, 2022;Sohroforouzani et al, 2022) and clinical (Oberste et al, 2020) findings. Although the FSL rat is not known to display increased anxiety-like behaviour (Overstreet & Wegener, 2013), pre-pubertal low-intensity exercise appeared to induce anxiolytic-like effects in FSL rats on PND37 (Fig.…”

Section: The Influence Of Pre-pubertal Low-intensity Exercisesupporting

confidence: 87%

“…The antidepressant effects of exercise have been widely established (Carter et al, 2016;Kandola et al, 2019), yet the exact mechanisms through which it exerts its antidepressant effects remain unknown (Schuch et al, 2016). Numerous mechanisms have been proposed (Kandola et al, 2019;de Oliveira et al, 2022) and include (but are not limited to) increased monoamine neurotransmission (Lin & Kuo, 2013) and neuroplasticity (El-Sayes et al, 2019) and decreased inflammation and oxidative stress (Eyre & Baune, 2012), all of which have been implicated in the pathophysiology of depression and as alluded to earlier, linked to mitochondrial function (Allen et al, 2018;Sharma & Akundi, 2019;van Rensburg et al, 2022). Additionally, exercise also induces bio-energetic enhancing effects (i.e., improved mitochondrial functioning (Aguiar et al, 2014;Wu et al, 2019)).…”

Section: Introductionmentioning

confidence: 99%

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Running from depression: the antidepressant-like potential of prenatal and pre-pubertal exercise in adolescent FSL rats exposed to an early-life stressor

Whitney,

Lindeque,

Kruger

et al. 2023

Acta Neuropsychiatr.

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Objective: We aimed to answer the questions of whether early-life (perinatal and/or juvenile) exercise can induce antidepressant-like effects in a validated rodent model of depression, and whether such early-life intervention could prevent or reverse the adverse effects of early-life stress in their offspring. Methods: Male and female FSL rats born to a dam that exercised during gestation, or not, were either maternally separated between PND02 and 16 and weaned on PND17, or not. Half of these animals then underwent a fourteen-day low intensity exercise regimen from PND22. Baseline depressive-like behaviour was assessed on PND21 and then reassessed on PND36, whereafter hippocampal monoamine levels, redox state markers and metabolic markers, relevant to mitochondrial function were measured. Results: Prepubertal exercise was identified as the largest contributing factor to the observed effects, where it decreased immobility time in the FST by 6%, increased time spent in the open arms of the EPM by 9%. Hippocampal serotonin and norepinephrine levels were also increased by 35 and 26%, respectively, whilst nicotinic acid was significantly decreased. Conclusion: These findings suggests that prepubertal low intensity exercise induces beneficial biological alterations that could translate into antidepressant behaviour in genetically susceptible individuals.

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Section: The Influence Of Pre-pubertal Low-intensity Exercisesupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Running from depression: the antidepressant-like potential of prenatal and pre-pubertal exercise in adolescent FSL rats exposed to an early-life stressor

Whitney,

Lindeque,

Kruger

et al. 2023

Acta Neuropsychiatr.

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“…There is now much evidence on the physiological mechanisms underlying depression inhibition by physical exercise. In animal studies, physical exercise has been shown to promote elevated levels of antioxidant enzymes, brain-derived neurotransmitters, etc., and to reduce cortisol levels with reduced in ammation in brain tissue [19] . Neurobiology has shown that exercise increases the volume of grey matter in the brain, improves the microstructure of white matter, and is associated with functional connectivity in brain regions associated with major depression [20] .…”

Section: Discussionmentioning

confidence: 99%

Relationship between physical activity and risk of depression in a married group

Yang

2023

Preprint

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OBJECTIVE: To understand the relationship between physical activity behavior and depression risk in the married group from the perspective of gender differences. METHODS: The 15,607 married people in the China Family Tracking Survey 2020 (CFPS 2020) were used to investigate the relationship between physical activity and depression risk among different groups of people in marriage. Results: There were 527 (6.64%) women at high risk of depression, of whom 417 (7.71%) had no exercise habits, and 365 (4.76%) men at high risk of depression, of whom 279 (5.56%) had no exercise habits; physical exercise habits could influence the risk of depression among those in marriage, and after controlling for the relevant variables, physical exercise was negatively associated with the risk of depression among women (OR=0.5). After controlling for the relevant variables, physical activity was negatively associated with the risk of depression in women (OR=0.65, p<0.001), but not in men (OR=0.79, p>0.05). Conclusion:Physical activity moderates the risk of depression in married women, but is not directly associated with the risk of depression in married men.

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“…Among them, antidepressants are the most commonly used treatments for patients with depression. However, it is known that only 20%–40% of depressed patients respond to low doses of these drugs, and the risk of adverse effects increases with higher doses ( de Oliveira et al, 2022 ). Studies have found that herbal medicine has a strong antidepressant effect with few adverse reactions ( Wang et al, 2017 ; Chi et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Integrating Metabolomics and Network Analysis for Exploring the Mechanism Underlying the Antidepressant Activity of Paeoniflorin in Rats With CUMS-Induced Depression

et al. 2022

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Background: Paeoniflorin (PF) represents the major bioactive constituent of the traditional Chinese medicine plant Paeonia suffruticosa (Ranunculaceae), which has a long history as a folk medicine in Asian. Paeoniflorin, a bitter pinene monoterpene glycoside, has antidepressant effects, but its potential therapeutic mechanism has not been thoroughly explored.Methods: Experimental depression in rats was established by the chronic unpredictable mild stress (CUMS) combined with orphan method, and the efficacy of paeoniflorin on depression was evaluated by the sucrose preference test and open field test. The antidepressant mechanism of paeoniflorin was investigated by metabolomic and network pharmacology. The relevant pathways of biomarkers highlighted in metabolomics were explored, and the possible targets of paeoniflorin in the treatment of depression were further revealed through network analysis. The binding activity of paeoniflorin to key targets was verified by molecular docking.Results: Metabolomics showed that rats with CUMS-induced depression had urine metabolic disorders, which were reversed by paeoniflorin through the regulation of metabolic pathways. Metabolites that play a key role in the function of paeoniflorin include citric acid, thiamine monophosphate, gluconolactone, 5-hydroxyindoleacetic acid and stachyose. Key predicted targets are SLC6A4, TNF, IL6 and SLC6A3. An important metabolic pathway is the Citrate cycle (TCA cycle).Conclusion: Network integrative analysis in this study showed that paeoniflorin could improve depressive-like symptoms in model rats with CUMS-induced depression and overall correct the disordered metabolic profile through multiple metabolic pathways.

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An overview of the molecular and physiological antidepressant mechanisms of physical exercise in animal models of depression

Cited by 13 publications

References 107 publications

Running from depression: the antidepressant-like potential of prenatal and pre-pubertal exercise in adolescent FSL rats exposed to an early-life stressor

Running from depression: the antidepressant-like potential of prenatal and pre-pubertal exercise in adolescent FSL rats exposed to an early-life stressor

Relationship between physical activity and risk of depression in a married group

Integrating Metabolomics and Network Analysis for Exploring the Mechanism Underlying the Antidepressant Activity of Paeoniflorin in Rats With CUMS-Induced Depression

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