Mitochondrial transplantation attenuates lipopolysaccharide- induced depression-like behaviors

Wang, Yun; Ni, Jing; Gao, Ce; Xie, Liming; Zhai, Lingyan; Cui, Guiyun; Yin, Xiaoxing

doi:10.1016/j.pnpbp.2019.04.010

Cited by 71 publications

(39 citation statements)

References 43 publications

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“…Interestingly, chronic hyperglycemic incubation was found to impair both constitutive and regenerative neurogenesis in the telencephalon of the adult zebrafish (Dorsemans et al., 2017). Mitochondrial transfer therapy, the injection of exogenous mitochondria, ameliorated depressive‐like behavior, neuroinflammation, and boosted hippocampal BDNF expression in mice (Wang et al., 2019). Increased ROS is a prerequisite for inflammasome activation, such as the NLRP3 inflammasome which is responsible for triggering inflammation (Han et al., 2015).…”

Section: Physiological Factors That Play Key Roles In the Comorbiditymentioning

confidence: 99%

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control

Subba

Sandhir

Singh

et al. 2021

Eur J of Neuroscience

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Diabetes increases the likelihood of developing depression and vice versa. Research on this bidirectional association has somewhat managed to delineate the interplay among implicated physiological processes. Still, further exploration is required in this context. This review addresses the comorbidity by investigating suspected common pathophysiological mechanisms. One such factor is psychological stress which disturbs the hypothalamic–pituitary–adrenal axis causing hormonal imbalance. This includes elevated cortisol levels, a common biomarker of both depression and diabetes. Disrupted insulin signaling drives the hampered neurotransmission of serotonin, dopamine, and norepinephrine. Also, adipokine hormones such as adiponectin, leptin, and resistin and the orexigenic hormone, ghrelin, are involved in both depression and T2DM. This disarray further interferes with physiological processes encompassing sleep, the gut–brain axis, metabolism, and mood stability. Behavioral coping mechanisms, such as unhealthy eating, mediate disturbed glucose homeostasis, and neuroinflammation. This is intricately linked to oxidative stress, redox imbalance, and mitochondrial dysfunction. However, interventions such as psychotherapy, physical exercise, fecal microbiota transplantation, and insulin‐sensitizing agents can help to manage the distressing condition. The possibility of glucagon‐like peptide 1 possessing a therapeutic role has also been discussed. Nonetheless, there stands an urgent need for unraveling new correlating targets and biological markers for efficient treatment.

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Section: Physiological Factors That Play Key Roles In the Comorbiditymentioning

confidence: 99%

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control

Subba

Sandhir

Singh

et al. 2021

Eur J of Neuroscience

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“…with LPS (0.83 mg/kg) dissolved in sterile saline. The concentration of LPS was based on the results of previous studies (Tomaz et al, 2014;Taniguti et al, 2019;Wang et al, 2019a;Wang et al, 2019b). The animals were subjected to following behavioral tests 24 h after LPS.…”

Section: Drug Administration and Animal Experimental Proceduresmentioning

confidence: 99%

FGF21 Attenuated LPS-Induced Depressive-Like Behavior via Inhibiting the Inflammatory Pathway

Wang

Zhu

et al. 2020

Front. Pharmacol.

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Major depressive disorder is a serious neuropsychiatric disorder with high rates of recurrence and mortality. Many studies have supported that inflammatory processes play a central role in the etiology of depression. Fibroblast growth factor 21 (FGF21), a member of the fibroblast growth factors (FGFs) family, regulates a variety of pharmacological activities, including energy metabolism, glucose and lipid metabolism, and insulin sensitivity. In addition, recent studies showed that the administration of FGF21, a regulator of metabolic function, had therapeutic effects on mood stabilizers, indicating that FGF21 could be a common regulator of the mood response. However, few studies have highlighted the antidepressant effects of FGF21 on lipopolysaccharide (LPS)induced mice, and the anti-inflammatory mechanism of FGF21 in depression has not yet been elucidated. The purpose of the current study was to determine the antidepressant effects of recombinant human FGF21 (rhFGF21). The effects of rhFGF21 on depression-like behaviors and the inflammatory signaling pathway were investigated in both an LPS-induced mouse model and primary microglia in vitro. The current study demonstrated that LPS induced depressive-like behaviors, upregulated proinflammatory cytokines, and activated microglia in the mouse hippocampus and activated the inflammatory response in primary microglia, while pretreatment with rhFGF21 markedly improved depression-like behavior deficits, as shown by an increase in the total distance traveled and number of standing numbers in the open field test (OFT) and a decrease in the duration of immobility in the tail suspension test (TST) and forced swimming test (FST). Furthermore, rhFGF21 obviously suppressed expression levels of the proinflammatory cytokines interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) and inhibited microglial activation and the nuclear factor-kB (NF-kB) signing pathway. Moreover, coadministration of rhFGF21 with the fibroblast growth factor receptor 1 (FGFR1) inhibitor PD173074 significantly reversed these protective effects, indicating that the antidepressant effects of rhFGF21 occur through FGFR1 activation. Taken together, the results of the current study demonstrated for the first time that exogenous rhFGF21 ameliorated LPS-induced depressive-like behavior by inhibiting microglial Frontiers in Pharmacology | www.frontiersin.org February 2020 | Volume 11 | Article 154 1 expression of proinflammatory cytokines through NF-kB suppression. This new discovery suggests rhFGF21 as a new therapeutic candidate for depression treatment.

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“…In the previous study, we have suggested that mitotherapy could prevent Parkinson's disease in an experimental mouse model [17]. Besides, a current report confirms that exogenous mitochondria following intravenous administration can cross the blood-brain barrier (BBB) to treat depression in mice [ 31 ]. Although the mechanism of penetrating BBB of mitochondria remains unclear, it might be ascribed to a transcytosis pathway, which is a fundamental biological process used by macromolecules and particles to cross BBB [ 32 ].…”

Section: Discussionmentioning

confidence: 59%

Improvement of cognitive and motor performance with mitotherapy in aged mice

Zhao

Hou

et al. 2020

Int. J. Biol. Sci.

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Changes in mitochondrial structure and function are mostly responsible for aging and age-related features. Whether healthy mitochondria could prevent aging is, however, unclear. Here we intravenously injected the mitochondria isolated from young mice into aged mice and investigated the mitotherapy on biochemistry metabolism and animal behaviors. The results showed that heterozygous mitochondrial DNA (mtDNA) of both aged and young mouse coexisted in tissues of aged mice after mitochondrial administration, and meanwhile, ATP content in tissues increased while reactive oxygen species (ROS) level reduced. Besides, the mitotherapy significantly improved cognitive and motor performance of aged mice. Our study, at the first report in aged animals, not only provides a useful approach to study mitochondrial function associated with aging, but also a new insight into anti-aging through mitotherapy.

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Mitochondrial transplantation attenuates lipopolysaccharide- induced depression-like behaviors

Cited by 71 publications

References 43 publications

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control

FGF21 Attenuated LPS-Induced Depressive-Like Behavior via Inhibiting the Inflammatory Pathway

Improvement of cognitive and motor performance with mitotherapy in aged mice

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