Dysregulation of LIMK‐1/cofilin‐1 pathway: A possible basis for alteration of neuronal morphology in experimental cerebral malaria

Kumar, Simhadri Praveen; Malwade, Ruchi; Vanka, Ravisankar; Nakka, Venkata Prasuja; Kuppusamy, Gowthamarajan; Babu, Phanithi Prakash

doi:10.1002/ana.25028

Cited by 17 publications

(13 citation statements)

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“…As SD induced memory impairment and anxiety were confirmed, SD mice were subjected to Golgi staining as described previously [ 40 ]. Mice were anesthetized with pentobarbital sodium and brains were removed.…”

Section: Methodsmentioning

confidence: 99%

Ellagic acid protects mice against sleep deprivation-induced memory impairment and anxiety by inhibiting TLR4 and activating Nrf2

Wang

Yang

Liu

et al. 2020

Aging

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Sleep disorder has become a prevalent issue in current society and is connected with the deterioration of neurobehaviors such as mood, cognition and memory. Ellagic acid (EA) is a phenolic phytoconstituent extracted from grains and fruits that has potent neuroprotective properties. This research aimed to study the alleviative effect and mechanism of EA on memory impairment and anxiety caused by sleep deprivation (SD). EA ameliorated behavioral abnormalities in SD mice, associated with increased dendritic spine density, and reduced shrinkage and loss of hippocampal neurons. EA reduced the inflammatory response and oxidative stress injury caused by SD, which may be related to activation of the Nrf2/HO-1 pathway and mitigation of the TLR4-induced inflammatory response. In addition, EA significantly reduced the mortality and ROS levels in glutamate (Glu)-induced hippocampal neuron injury, and these effects of EA were enhanced in TLR4 siRNA-transfected neurons. However, knockdown of Nrf2 dramatically restrained the protective impact of EA on Glu-induced toxicity. Taken together, EA alleviated memory impairment and anxiety in sleep-deprived mice potentially by inhibiting TLR4 and activating Nrf2. Our findings suggested that EA may be a promising nutraceutical ingredient to prevent cognitive impairment and anxiety caused by sleep loss.

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Section: Methodsmentioning

confidence: 99%

Ellagic acid protects mice against sleep deprivation-induced memory impairment and anxiety by inhibiting TLR4 and activating Nrf2

Wang

Yang

Liu

et al. 2020

Aging

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“…In general, disruption of the blood–brain barrier, subsequent infiltration of immune cells, and hemorrhage are known to comprise a critical mechanism of CM that can cause nerve tissue damage [ 4 ]. Previous research has shown that neuronal damage can lead to neurological sequelae in children with CM and mice with experimental cerebral malaria (ECM) [ 5 – 7 ], but the underlying mechanism remains unclear. Recently, significantly increased levels of oxidative stress were detected in patients with severe malaria, including those with CM [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis participates in neuron damage in experimental cerebral malaria and is partially induced by activated CD8+ T cells

Shen

Wang

et al. 2022

Mol Brain

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Cerebral malaria is the most serious complication of malaria infection, with 26% of surviving children having neurological sequelae, which may be caused by neuron damage, but the mechanism is not clear. Ferroptosis has been reported to play an important role in neuron damage in several nervous system diseases. However, the occurrence of ferroptosis in experimental cerebral malaria (ECM) pathogenesis is still unknown. In this study, we firstly detected increased levels of malondialdehyde (MDA) and iron, which are indicators of ferroptosis, in the cerebrum of ECM mice. Some important regulators of ferroptosis, including upregulated expression of transferrin receptor 1 (TfR1) and acyl-CoA synthetase long-chain family member 4 (ACSL4), and downregulation of glutathione peroxidase 4 (GPX4) levels, were also confirmed in ECM mice. Consistently, neuron damage, which was detected in the cerebrum of ECM mice, was positively correlated with reduced GPX4 expression and furtherly rescued by administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1). In addition, primary neurons were damaged by activated CD8+ T cells, an effect that was also partially rescued by Fer-1 on amyloid precursor protein expression and mitochondrial membrane potential levels in vitro. Activated CD8+ T cells were also shown to infiltrate the cerebrum of ECM mice and upregulate TfR1 expression in primary neurons, which may be an important event for inducing ferroptosis in ECM. Altogether, we show that ferroptosis contributes to neuron damage in ECM pathogenesis, and activated CD8+ T cells may be important inducers of neuronal ferroptosis. Hence, targeting ferroptosis may be a promising adjuvant therapeutic strategy for neurological sequelae in patients with cerebral malaria.

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“…In addition, PPARγ has shown neuroprotective effects via various pathways and promotes neuronal repair, making it an attractive adjuvant therapy. Dysregulation of the limk-1/cofilin-1 pathway might lead to alterations in neuronal morphology and is considered the cause of cognitive defects in patients surviving CM ( Simhadri et al., 2017 ); therefore, the LIMK-1/cofilin-1 pathway is considered a potential therapeutic target for CM. In addition, granzyme-B produced by CD8 + T cells directly kills neurons through cytotoxic function and activation of caspase-3 and calpain1 ( Kaminski et al., 2019 ).…”

Section: Treatmentmentioning

confidence: 99%

Cerebral malaria induced by plasmodium falciparum: clinical features, pathogenesis, diagnosis, and treatment

Song

Wei

Cheng

et al. 2022

Front. Cell. Infect. Microbiol.

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Cerebral malaria (CM) caused by Plasmodium falciparum is a fatal neurological complication of malaria, resulting in coma and death, and even survivors may suffer long-term neurological sequelae. In sub-Saharan Africa, CM occurs mainly in children under five years of age. Although intravenous artesunate is considered the preferred treatment for CM, the clinical efficacy is still far from satisfactory. The neurological damage induced by CM is irreversible and lethal, and it is therefore of great significance to unravel the exact etiology of CM, which may be beneficial for the effective management of this severe disease. Here, we review the clinical characteristics, pathogenesis, diagnosis, and clinical therapy of CM, with the aim of providing insights into the development of novel tools for improved CM treatments.

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Dysregulation of LIMK‐1/cofilin‐1 pathway: A possible basis for alteration of neuronal morphology in experimental cerebral malaria

Cited by 17 publications

References 50 publications

Ellagic acid protects mice against sleep deprivation-induced memory impairment and anxiety by inhibiting TLR4 and activating Nrf2

Ellagic acid protects mice against sleep deprivation-induced memory impairment and anxiety by inhibiting TLR4 and activating Nrf2

Ferroptosis participates in neuron damage in experimental cerebral malaria and is partially induced by activated CD8+ T cells

Cerebral malaria induced by plasmodium falciparum: clinical features, pathogenesis, diagnosis, and treatment

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