Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced Hippocampus and Frontal cortex damage in mice: Role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling

Kwatra, Mohit; Ahmed, Sahabuddin; Gawali, Basveshwar; Panda, Samir Ranjan; Naidu, V.G.M.

doi:10.1016/j.neuint.2020.104835

Cited by 37 publications

(18 citation statements)

References 35 publications

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“…NF-kB plays a role in inflammation and synaptic plasticity [4,45], but it is also connected to mood disorders [46]. P38 MAPK signaling pathway activation is known to be involved in various stress responses [47,48], as well as in cognitive dysfunction and synaptic plasticity [49]. In vivo, pharmacological inhibition of p38 MAPK yielded significant anti-anxiety-like activity [50], whereas in vitro, the expression of CD24 was correlated with activation of ERK1/2 and p38 MAPK [4].…”

Section: Discussionmentioning

confidence: 99%

Behavioral Characterizing of CD24 Knockout Mouse—Cognitive and Emotional Alternations

Nitzan

Toledano

Shapira

et al. 2021

JPM

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CD24 is a small, glycophosphatidylinositol-anchored cell surface protein, mostly investigated with respect to cancer, inflammation, and autoimmune diseases. CD24 knockdown or inhibition has been used to test various biochemical mechanisms and neurological conditions; however, the association between CD24 and behavioral phenotypes has not yet been examined. This study aims to characterize cognitive and emotional functions of CD24 knockout mice (CD24−/−) compared with CD24 wild-type mice at three time-points: adolescence, young adulthood, and adulthood. Our results show that CD24−/− mice exhibited better cognitive performance and less anxiety-like behavior compared with WT mice, with no effect on depression-like behavior. This phenotype was constant from childhood (2 months old) to adulthood (6 months old). The results from our study suggest that CD24 may influence important behavioral aspects at the whole-organism level, which should be taken into consideration when using CD24 knockout models.

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Section: Discussionmentioning

confidence: 99%

Behavioral Characterizing of CD24 Knockout Mouse—Cognitive and Emotional Alternations

Nitzan

Toledano

Shapira

et al. 2021

JPM

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“…Microglia are the resident immune cells within the brain that plays a fundamental role in maintenance of neuronal survival by phagocytising and eliminating cytotoxic insults [39]. Substantial evidences concluded chronic and persistent microglia activation function as a key regulator in initiating neurodegeneration in several neurological diseases including PD [40][41][42]15]. This statement was further proven by the post-mortem brain analysis of patients suffering from PD was found with activated microglia in SNpc region where dopaminergic neurons are mostly concentrated [43].…”

Section: Discussionmentioning

confidence: 92%

Pharmacological Blocker of NF-κb and Mitochondrial Ros Restrict NLRP3 Inflammasome Activation and Rescue Dopaminergic Neurons in Vitro and in Vivo Parkinson’s Disease

Ahmed

Panda

Kwatra

et al. 2021

Preprint

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Several activators of NLRP3 inflammasome have been described; however, the central mechanisms of NLRP3 inflammasome activation in brain microglia, especially at the activating step through free radical generation, still require further clarification. Hence the present study aimed to investigate the role of free radicals in activating NLRP3 inflammasome driven neurodegeneration and elucidated the neuroprotective role of perillyl alcohol (PA) in vitro and in vivo models of Parkinson’s disease. Initial priming of microglial cells with lipopolysaccharide (LPS) following treatment with hydrogen peroxide (H2O2) induces NF-κB translocation to nucleus with robust generation of free radicals that act as Signal 2 in augmenting NLRP3 inflammasome assembly and its downstream targets. PA treatment suppresses nuclear translocation of NF-κB and maintains cellular redox homeostasis in microglia that limits NLRP3 inflammasome activation along with processing active caspase-1, IL-1β and IL-18. To further correlates the in vitro study with in vivo MPTP model, treatment with PA also inhibits the nuclear translocation of NF-κB and downregulates the NLRP3 inflammasome activation. PA administration upregulates various antioxidant enzymes levels and restored the level of dopamine and other neurotransmitters in the striatum of the mice brain with improved behavioural activities. Additionally, treatment with Mito-TEMPO (a mitochondrial ROS inhibitor) was also seen to inhibit NLRP3 inflammasome and rescue dopaminergic neuron loss in the mice brain. Therefore, we conclude that NLRP3 inflammasome activation requires a signal from damaged mitochondria for its activation. Further pharmacological scavenging of free radicals restricts microglia activation and simultaneously supports neuronal survival via targeting NLRP3 inflammasome pathway in Parkinson’s disease.

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“…Sickness behavior is a set of neuroimmune and behavioral‐specific changes induced by inflammatory/infectious processes and characterized by prostration, decreases in exploratory activity, and increase in peripheral and central pro‐inflammatory mediators and biomarkers (Dantzer & Kelley, 2007; Larson & Dunn, 2001). Indeed, it is known that LPS induces sickness behavior in rats and mice, decreasing open‐field activity and increasing GFAP expression (Kirsten et al, 2020; Kirsten, Galvao, et al, 2015; Kwatra et al, 2020; Moraes et al, 2017; Yeh et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Bate palmas mutant mice as a model of Kabuki syndrome: Higher susceptibility to infections and vocalization impairments?

Kirsten

Silva

Biondi

et al. 2022

J of Neuroscience Research

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The recessive mutant mouse bate palmas (bapa) arose from N-ethyl-N-nitrosourea mutagenesis. Previous studies of our group revealed some behavioral impairments and a mutation in the lysine (K)-specific methyltransferase 2D (Kmt2d) gene. Because mutations in the KMT2D gene in humans are mainly responsible for Kabuki syndrome, this study was proposed to validate bapa mice as a model of Kabuki syndrome.Besides other symptoms, Kabuki syndrome is characterized by increased susceptibility to infections and speech impairments, usually diagnosed in the early childhood. Thus, juvenile male and female bapa mice were studied in different developmental stages (prepubertal period and puberty). To induce sickness behavior and to study infection susceptibility responses, lipopolysaccharide (LPS) was used. To study oral communication, ultrasonic vocalizations were evaluated. Behavioral (open-field test) and central (astrocytic glial fibrillary acidic protein [GFAP] and tyrosine hydroxylase [TH]) evaluations were also performed. Control and bapa female mice emitted 31-kHz ultrasounds on prepubertal period when exploring a novel environment, a frequency not yet described for mice, being defined as 31-kHz exploratory vocalizations. Males, LPS, and puberty inhibited these vocalizations. Bapa mice presented increased motor/ exploratory behaviors on prepubertal period due to increased striatal TH expression, revealing striatal dopaminergic system hyperactivity. Combining open-field behavior and GFAP expression, bapa mice did not develop LPS tolerance, that is, they remained expressing signs of sickness behavior after LPS challenge, being more susceptible to infectious/inflammatory processes. It was concluded that bapa mice is a robust experimental model of Kabuki syndrome.

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Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced Hippocampus and Frontal cortex damage in mice: Role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling

Cited by 37 publications

References 35 publications

Behavioral Characterizing of CD24 Knockout Mouse—Cognitive and Emotional Alternations

Behavioral Characterizing of CD24 Knockout Mouse—Cognitive and Emotional Alternations

Pharmacological Blocker of NF-κb and Mitochondrial Ros Restrict NLRP3 Inflammasome Activation and Rescue Dopaminergic Neurons in Vitro and in Vivo Parkinson’s Disease

Bate palmas mutant mice as a model of Kabuki syndrome: Higher susceptibility to infections and vocalization impairments?

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Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced Hippocampus and Frontal cortex damage in mice: Role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling

Cited by 37 publications

References 35 publications

Behavioral Characterizing of CD24 Knockout Mouse—Cognitive and Emotional Alternations

Behavioral Characterizing of CD24 Knockout Mouse—Cognitive and Emotional Alternations

Pharmacological Blocker of NF-κb and Mitochondrial Ros Restrict NLRP3&nbsp;Inflammasome Activation and Rescue Dopaminergic Neurons in Vitro and in Vivo Parkinson’s Disease

Bate palmas mutant mice as a model of Kabuki syndrome: Higher susceptibility to infections and vocalization impairments?

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Pharmacological Blocker of NF-κb and Mitochondrial Ros Restrict NLRP3 Inflammasome Activation and Rescue Dopaminergic Neurons in Vitro and in Vivo Parkinson’s Disease