Protective Effects of Melatonin on Methamphetamine-Induced Blood–Brain Barrier Dysfunction in Rat Model

Namyen, Jatuporn; Permpoonputtana, Kannika; Nopparat, Chutikorn; Tocharus, Jiraporn; Tocharus, Chainarong; Govitrapong, Piyarat

doi:10.1007/s12640-019-00156-1

Cited by 44 publications

(23 citation statements)

References 53 publications

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“…The role of oxidative stress in inducing BBB injury has been widely recognized (Pun et al, 2009;Northrop and Yamamoto, 2015;Namyen et al, 2020). Toborek et al (Toborek et al, 2003) suggested that the increase of cellular oxidative stress may be a mechanism of BBB injury induced by HIV-Tat.…”

Section: Discussionmentioning

confidence: 99%

“…However, when METH and HIV-Tat induce neurotoxicity, BBB injury often occurs. Several studies have shown that both METH and HIV-Tat can induce BMEC apoptosis (Ma et al, 2014;Jumnongprakhon et al, 2016;Jumnongprakhon et al, 2017;Qie et al, 2017), destroy the BMEC cytoskeleton (Avraham et al, 2004;Fernandes et al, 2014;Xue et al, 2019), reduce BMEC transepithelial electrical resistance (TEER) (Jumnongprakhon et al, 2016;Patel et al, 2017;Qie et al, 2017), and affect the expression and function of TJ proteins (Xu et al, 2012;Fernandes et al, 2014;Jiang et al, 2017b;Gonçalves et al, 2017;Qie et al, 2017;Xue et al, 2019), thus altering the BBB's permeability and destroying its structural integrity (Mcrae, 2016;Namyen et al, 2020). Moreover, when a combined exposure of both METH and HIV-Tat, the consequent BMEC damage and abnormal TJ protein expression are more serious (Patel et al, 2017;Li et al, 2018b).…”

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confidence: 99%

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Methamphetamine and HIV-Tat Protein Synergistically Induce Oxidative Stress and Blood-Brain Barrier Damage via Transient Receptor Potential Melastatin 2 Channel

et al. 2021

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Synergistic impairment of the blood-brain barrier (BBB) induced by methamphetamine (METH) and HIV-Tat protein increases the risk of HIV-associated neurocognitive disorders (HAND) in HIV-positive METH abusers. Studies have shown that oxidative stress plays a vital role in METH- and HIV-Tat-induced damage to the BBB but have not clarified the mechanism. This study uses the human brain microvascular endothelial cell line hCMEC/D3 and tree shrews to investigate whether the transient receptor potential melastatin 2 (TRPM2) channel, a cellular effector of the oxidative stress, might regulate synergistic damage to the BBB caused by METH and HIV-Tat. We showed that METH and HIV-Tat damaged the BBB in vitro, producing abnormal cell morphology, increased apoptosis, reduced protein expression of the tight junctions (TJ) including Junctional adhesion molecule A (JAMA) and Occludin, and a junctional associated protein Zonula occludens 1 (ZO1), and increased the flux of sodium fluorescein (NaF) across the hCMEC/D3 cells monolayer. METH and HIV-Tat co-induced the oxidative stress response, reducing catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activity, as well as increased reactive oxygen species (ROS) and malonaldehyde (MDA) level. Pretreatment with n-acetylcysteine amide (NACA) alleviated the oxidative stress response and BBB damage characterized by improving cell morphology, viability, apoptosis levels, TJ protein expression levels, and NaF flux. METH and HIV-Tat co-induced the activation and high protein expression of the TRPM2 channel, however, early intervention using 8-Bromoadenosine-5′-O-diphosphoribose (8-Br-ADPR), an inhibitor of TPRM2 channel, or TRPM2 gene knockdown attenuated the BBB damage. Oxidative stress inhibition reduced the activation and high protein expression of the TRPM2 channel in the in vitro model, which in turn reduced the oxidative stress response. Further, 8-Br-ADPR attenuated the effects of METH and HIV-Tat on the BBB in tree shrews—namely, down-regulated TJ protein expression and increased BBB permeability to Evans blue (EB) and NaF. In summary, the TRPM2 channel can regulate METH- and HIV-Tat-induced oxidative stress and BBB injury, giving the channel potential for developing drug interventions to reduce BBB injury and neuropsychiatric symptoms in HIV-infected METH abusers.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Methamphetamine and HIV-Tat Protein Synergistically Induce Oxidative Stress and Blood-Brain Barrier Damage via Transient Receptor Potential Melastatin 2 Channel

et al. 2021

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“…Downstream signaling that is inhibited by melatonin can concern different pathway branches, in particular, the phosphorylation of Akt, mTOR [ 37 , 40 ], and the stress kinases JNK and p38 [ 37 , 40 ]; the prevention of NADPH oxidase activation/assembly [ 38 , 40 , 41 ]; and the prevention of caspase-3 cleavage [ 35 , 36 , 42 ]. As a common feature that is observed throughout practically all pertinent studies, the suppression of NF-κB activation, which was often accompanied by Nrf2 upregulation, reflects the anti-inflammatory and antioxidant actions of melatonin in microglia [ 26 , 32 , 36 , 38 , 39 , 43 , 44 , 45 , 46 , 47 , 48 ]. Conversely, the suppression of melatonin secretion by sleep deprivation enhanced microglia activation, which was evident from proinflammatory traits such as NF-κB activation, JNK phosphorylation, the upregulation of NADPH oxidases 1, 2, and 4, and the release of proinflammatory cytokines [ 49 ].…”

Section: Melatonin Suppresses Proinflammatory and Favors Anti-inflammatory Signalingmentioning

confidence: 99%

Melatonin and Microglia

Hardeland

2021

IJMS

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Melatonin interacts in multiple ways with microglia, both directly and, via routes of crosstalk with astrocytes and neurons, indirectly. These effects of melatonin are of relevance in terms of antioxidative protection, not only concerning free-radical detoxification, but also in prevention of processes that cause, promote, or propagate oxidative stress and neurodegeneration, such as overexcitation, toxicological insults, viral and bacterial infections, and sterile inflammation of different grades. The immunological interplay in the CNS, with microglia playing a central role, is of high complexity and includes signaling toward endothelial cells and other leukocytes by cytokines, chemokines, nitric oxide, and eikosanoids. Melatonin interferes with these processes in multiple signaling routes and steps. In addition to canonical signal transduction by MT1 and MT2 melatonin receptors, secondary and tertiary signaling is of relevance and has to be considered, e.g., via the upregulation of sirtuins and the modulation of pro- and anti-inflammatory microRNAs. Many details concerning the modulation of macrophage functionality by melatonin are obviously also applicable to microglial cells. Of particular interest is the polarization toward M2 subtypes instead of M1, i.e., in favor of being anti-inflammatory at the expense of proinflammatory activities, which is well-documented in macrophages but also applies to microglia.

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“…By attenuating the loss of tight junctions and inhibition of MMP-9 [117], melatonin's neuroprotective effects are preserved. It has also been demonstrated in methamphetamine-administered rats that melatonin prevents drug-induced structural impairments in the BBB, along with decrements in the pro-inflammatory cytokines such as IL-1β, interleukin-6 (IL-6), TNF-α, NF-κB and nuclear factor erythroid 2-related factor (Nrf2) signaling, which are involved in antioxidant defense [118]; these same actions have been documented in glioma cell lines [119] and human neuroblastoma cells [120].…”

Section: Melatonin As a Potential Neuroimmune Modulator In Viral Infectionmentioning

confidence: 99%

Role of Melatonin on Virus-Induced Neuropathogenesis—A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection

et al. 2021

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Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and encephalitis are common. Recently, extensive research-based studies have revealed and acknowledged the clinical and preventive roles of melatonin in some viral diseases. Melatonin has been shown to have antiviral properties against several viral infections which are accompanied by neurological symptoms. The beneficial properties of melatonin relate to its properties as a potent antioxidant, anti-inflammatory, and immunoregulatory molecule and its neuroprotective effects. In this review, what is known about the therapeutic role of melatonin in virus-induced neuropathogenesis is summarized and discussed.

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Protective Effects of Melatonin on Methamphetamine-Induced Blood–Brain Barrier Dysfunction in Rat Model

Cited by 44 publications

References 53 publications

Methamphetamine and HIV-Tat Protein Synergistically Induce Oxidative Stress and Blood-Brain Barrier Damage via Transient Receptor Potential Melastatin 2 Channel

Methamphetamine and HIV-Tat Protein Synergistically Induce Oxidative Stress and Blood-Brain Barrier Damage via Transient Receptor Potential Melastatin 2 Channel

Melatonin and Microglia

Role of Melatonin on Virus-Induced Neuropathogenesis—A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection

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