Leptin Attenuates Fear Memory by Inhibiting Astrocytic NLRP3 Inflammasome in Post-traumatic Stress Disorder Model

Ji, Ming; Gong, Wenliang; Wang, Siman; Zhang, Dianjun; Chen, Binjie; Li, Xinyu; Wu, Xiafang; Cui, Lulu; Feng, Yuliang; Verkhratsky, Alexei

doi:10.1007/s11064-022-03655-4

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…Leptin effectively improved these behavioral alterations including cognitive impairments and depressive-like conducts. These actions of leptin were facilitated by STAT3 [ 122 ]. An increase in STAT3 also mediates the effect of leptin in promoting angiogenesis after hemorrhage.…”

Section: Functionality Of Leptin and Its Involvement In Pathologymentioning

confidence: 99%

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

Casado

Collado-Pérez

Frago

et al. 2023

IJMS

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Excess body weight is frequently associated with low-grade inflammation. Evidence indicates a relationship between obesity and cancer, as well as with other diseases, such as diabetes and non-alcoholic fatty liver disease, in which inflammation and the actions of various adipokines play a role in the pathological mechanisms involved in these disorders. Leptin is mainly produced by adipose tissue in proportion to fat stores, but it is also synthesized in other organs, where leptin receptors are expressed. This hormone performs numerous actions in the brain, mainly related to the control of energy homeostasis. It is also involved in neurogenesis and neuroprotection, and central leptin resistance is related to some neurological disorders, e.g., Parkinson’s and Alzheimer’s diseases. In peripheral tissues, leptin is implicated in the regulation of metabolism, as well as of bone density and muscle mass. All these actions can be affected by changes in leptin levels and the mechanisms associated with resistance to this hormone. This review will present recent advances in the molecular mechanisms of leptin action and their underlying roles in pathological situations, which may be of interest for revealing new approaches for the treatment of diseases where the actions of this adipokine might be compromised.

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Section: Functionality Of Leptin and Its Involvement In Pathologymentioning

confidence: 99%

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

Casado

Collado-Pérez

Frago

et al. 2023

IJMS

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“…The cortices from three mice were pooled into one sample. The labelled cells were sorted and collected using the BD FACSAria Cell Sorting System (San Jose, CA) [17,24]. The purity of sorted astrocytes was ascertained by detecting mRNA of the cell-specific marker as described previously [13,23,25,26].…”

Section: Fluorescence-activated Cell Sorter (Facs)mentioning

confidence: 99%

A novel murine model of mania

Chen

Zhang

et al. 2023

Mol Psychiatry

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Neuropathological mechanisms of manic syndrome or manic episodes in bipolar disorder remain poorly characterised, as the research progress is severely limited by the paucity of appropriate animal models. Here we developed a novel mania mice model by combining a series of chronic unpredictable rhythm disturbances (CURD), which include disruption of circadian rhythm, sleep deprivation, exposure to cone light, with subsequent interference of followed spotlight, stroboscopic illumination, high-temperature stress, noise disturbance and foot shock. Multiple behavioural and cell biology tests comparing the CURD-model with healthy controls and depressed mice were deployed to validate the model. The manic mice were also tested for the pharmacological effects of various medicinal agents used for treating mania. Finally, we compared plasma indicators of the CURD-model mice and the patients with the manic syndrome. The CURD protocol produced a phenotype replicating manic syndrome. Mice exposed to CURD presented manic behaviours similar to that observed in the amphetamine manic model. These behaviours were distinct from depressive-like behaviours recorded in mice treated with a depression-inducing protocol of chronic unpredictable mild restraint (CUMR). Functional and molecular indicators in the CURD mania model showed multiple similarities with patients with manic syndrome. Treatment with LiCl and valproic acid resulted in behavioural improvements and recovery of molecular indicators. A novel manic mice model induced by environmental stressors and free from genetic or pharmacological interventions is a valuable tool for research into pathological mechanisms of mania.

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“…There is an increasing body of evidence that activation of the NLRP3 inflammasome plays a crucial role in the pathophysiology of PTSD and the development of brain inflammation. For example, higher expression of NLRP3 and caspase-1 was observed in astrocytes of mice with PTSD-like behavior ( Ji et al, 2022 ). This suggests that the NLRP3 inflammasome pathway was indeed activated in nervous tissue under PTSD conditions with a concomitant increase in ROS levels in mitochondria.…”

Section: Introductionmentioning

confidence: 99%

“…However, there is the study linking PTSD treatment to inflammation and mitochondria. In 2022, scientists proposed leptin as a candidate for the pharmacological treatment of PTSD ( Ji et al, 2022 ). First, this was due to the disclosed fact that administration of leptin to mice with PTSD-like symptoms, decreased the level of ROS, increased the level of ATP in astrocytic mitochondria, and inhibited the activation of astrocytic NLRP3 inflammasomes.…”

Section: Introductionmentioning

confidence: 99%

“…First, this was due to the disclosed fact that administration of leptin to mice with PTSD-like symptoms, decreased the level of ROS, increased the level of ATP in astrocytic mitochondria, and inhibited the activation of astrocytic NLRP3 inflammasomes. Second, leptin was associated with effective improvements in behavioral responses, including fear memory, cognitive impairment, and depressive-like behavior ( Ji et al, 2022 ). In another study ( Garabadu et al, 2015 ), scientists evaluated the drugs called Risperidone and Paroxetine, to assess their effects on mitochondrial dysfunction and mitochondrial-dependent apoptosis in specific brain regions in a modified rat model of PTSD.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial dysfunction as a possible trigger of neuroinflammation at post-traumatic stress disorder (PTSD)

Dmytriv,

Tsiumpala,

Semchyshyn

et al. 2023

Front. Physiol.

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Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that occurs in approximately 15% of people as a result of some traumatic events. The main symptoms are re-experiencing and avoidance of everything related to this event and hyperarousal. The main component of the pathophysiology of PTSD is an imbalance in the functioning of the hypothalamic-pituitary-adrenal axis (HPA) and development of neuroinflammation. In parallel with this, mitochondrial dysfunction is observed, as in many other diseases. In this review, we focus on the question how mitochondria may be involved in the development of neuroinflammation and its maintaining at PTSD. First, we describe the differences in the operation of the neuro-endocrine system during stress versus PTSD. We then show changes in the activity/expression of mitochondrial proteins in PTSD and how they can affect the levels of hormones involved in PTSD development, as well as how mitochondrial damage/pathogen-associated molecule patterns (DAMPs/PAMPs) trigger development of inflammation. In addition, we examine the possibility of treating PTSD-related inflammation using mitochondria as a target.

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Leptin Attenuates Fear Memory by Inhibiting Astrocytic NLRP3 Inflammasome in Post-traumatic Stress Disorder Model

Cited by 9 publications

References 37 publications

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

A novel murine model of mania

Mitochondrial dysfunction as a possible trigger of neuroinflammation at post-traumatic stress disorder (PTSD)

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