Curcumin induced up-regulation of Myelin basic protein (MBP) ameliorates sodium arsenite induced neurotoxicity in developing rat cerebellum

Kaushal, Parul; Mehra, Reeti; Dhar, Pushpa

doi:10.1016/j.jasi.2014.04.001

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…These data were in line with other studies demonstrating that decrease in MBP loss is associated with neuroprotection of white matter following neonatal HI injury (Carlsson et al, 2012; Cui et al, 2017). Our data were also in line with the results from other groups registering maintenance of myelin structure and upregulation of MBP expression in the cerebellar white matter in a model of sodium arsenite induced neurotoxicity in developing rat cerebellum (Kaushal et al, 2014). Surprisingly, we did not register similar effect in females (Figure 3I), which was also reflected in the combined (males + females) assessment (Figure 3J).…”

Section: Discussionsupporting

confidence: 92%

Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury

Rocha‐Ferreira

Sisa²,

Bright³

et al. 2019

Front. Physiol.

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Hypoxic-ischemic encephalopathy (HIE) is a major cause of mortality and morbidity in neonates, with an estimated global incidence of 3/1,000 live births. HIE brain damage is associated with an inflammatory response and oxidative stress, resulting in the activation of cell death pathways. At present, therapeutic hypothermia is the only clinically approved treatment available for HIE. This approach, however, is only partially effective. Therefore, there is an unmet clinical need for the development of novel therapeutic interventions for the treatment of HIE. Curcumin is an antioxidant reactive oxygen species scavenger, with reported anti-tumor and anti-inflammatory activity. Curcumin has been shown to attenuate mitochondrial dysfunction, stabilize the cell membrane, stimulate proliferation, and reduce injury severity in adult models of spinal cord injury, cancer, and cardiovascular disease. The role of curcumin in neonatal HIE has not been widely studied due to its low bioavailability and limited aqueous solubility. The aim of this study was to investigate the effect of curcumin treatment in neonatal HIE, including time of administration and dose-dependent effects. Our results indicate that curcumin administration prior to HIE in neonatal mice elevated cell and tissue loss, as well as glial activation compared to HI alone. However, immediate post-treatment with curcumin was significantly neuroprotective, reducing grey and white matter tissue loss, TUNEL+ cell death, microglia activation, reactive astrogliosis, and iNOS oxidative stress when compared to vehicle-treated littermates. This effect was dose-dependent, with 200 μg/g body weight as the optimal dose-regimen, and was maintained when curcumin treatment was delayed by 60 or 120 min post-HI. Cell proliferation measurements showed no changes between curcumin and HI alone, suggesting that the protective effects of curcumin on the neonatal brain following HI are most likely due to curcumin’s anti-inflammatory and antioxidant properties, as seen in the reduced glial and iNOS activity. In conclusion, this study suggests curcumin as a potent neuroprotective agent with potential for the treatment of HIE. The delayed application of curcumin further increases its clinical relevance.

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Section: Discussionsupporting

confidence: 92%

Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury

Rocha‐Ferreira

Sisa²,

Bright³

et al. 2019

Front. Physiol.

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“…In the present study, the dose of NaAsO 2 (1.5 and 2.5 mg/kg bw) approximately equivalent to 9.5 and 16% of its LD50 was used. Similar doses for evaluation of iAs induced toxicity have been used in previous studies [19] , [20] , [21] , [22] , [23] , [24] . The doses of ALA (70 mg/kg bw) and Cur (150 mg/kg bw) were adopted from reported literature [22] , [25] .…”

Section: Methodsmentioning

confidence: 99%

“…Cryocut (HS 525, Microm GmbH, Germany) sagittal sections (30 μm) of the cerebellum were processed for standardized free floating imunohistochemical technique [24] . Specific monoclonal antibodies: Synaptophysin (Syp: SantaCruz Biotechnology.…”

Section: Methodsmentioning

confidence: 99%

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Ameliorative role of antioxidant supplementation on sodium-arsenite induced adverse effects on the developing rat cerebellum

Kaushal

Kumar

Dhar

2020

Journal of Ayurveda and Integrative Medicine

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Background Arsenic is an environmental contaminant of global concern. Consumption of ground water contaminated with inorganic arsenic (iAs) continues to be the major source of its exposure. The developing nervous system is especially vulnerable to environmental insults due to its higher rate of oxygen consumption and provision of weaker antioxidant (AOX) machinery. Objective Since oxidative stress has been reported as one of the major factors underlying iAs induced toxicity, the aim of the present study is to study the effect of two AOXs i.e., Alpha Lipoic Acid (ALA) and Curcumin (Cur) in developing cerebellum of rats exposed to arsenic during postnatal period. Materials and Methods The study was carried out on mother reared neonatal rat pups grouped as normal (Ia) and sham (vehicle) controls (Ib,c,d), while the experimental groups IIa/ IIb received sodium arsenite (NaAsO2) [(1.5/2.5 mg/kg body weight (bw)] alone or along with ALA (70 mg/kg bw)- IIIa/ IIIb or along with Cur (150 mg/kg bw)- IVa/ IVb. Behavioural, biochemical and immunohistochemical procedures were carried out to understand the underlying mechanisms. Results The observations indicated deficits in locomotor function, accumulation of iAs, increased levels of oxidative stress markers along with downregulation of the expression of proteins closely associated with synaptic functioning (Synaptophysin and Postsynaptic density protein95) in the cerebellum of iAs treated animals. Substantial recovery in all these parameters was observed in AOX co-treated groups. Conclusion Our results support the potential of ALA and Cur in amelioration of iAs induced developmental neurotoxicity. ALA and Cur can be proposed as dietary adjuvants amongst populations inhabiting areas with high iAs contamination as a safe and cost effective antidotes.

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Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS)

et al. 2015

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Multiple sclerosis (MS) is a chronic progressive, neurological disease characterized by the targeted immune system-mediated destruction of central nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells secrete a variety of inflammatory cytokines that foster the breakdown of blood-brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they become reactivated upon exposure to the myelin structural proteins and continue to produce inflammatory cytokines such as tumor necrosis factor α (TNFα) that leads to direct activation of antibodies and macrophages that are involved in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs) migrating to the lesion sites are capable of acute remyelination but unable to completely repair or restore the immune system-mediated myelin damage. This results in various permanent clinical neurological disabilities such as cognitive dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At present, there is no cure for MS. Recent remyelination and/or myelin repair strategies have focused on the role of the neurotrophin brain-derived neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG binding protein (MeCP2). Research in the field of epigenetic therapeutics involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2. This review will address the role of MeCP2 and BDNF in remyelination and/or myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic interventions for MS.

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Curcumin induced up-regulation of Myelin basic protein (MBP) ameliorates sodium arsenite induced neurotoxicity in developing rat cerebellum

Cited by 5 publications

References 38 publications

Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury

Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury

Ameliorative role of antioxidant supplementation on sodium-arsenite induced adverse effects on the developing rat cerebellum

Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS)

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