Browsing by Author "Anubhuti Dixit"

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Minocycline, levodopa and MnTMPyP induced changes in the mitochondrial proteome profile of MPTP and maneb and paraquat mice models of Parkinson's disease
(2013) Anubhuti Dixit; Garima Srivastava; Divya Verma; Manisha Mishra; Pradhyumna Kumar Singh; Om Prakash; Mahendra Pratap Singh
Mitochondrial dysfunction is the foremost perpetrator of the nigrostriatal dopaminergic neurodegeneration leading to Parkinson's disease (PD). However, the roles played by majority of the mitochondrial proteins in PD pathogenesis have not yet been deciphered. The present study investigated the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and combined maneb and paraquat on the mitochondrial proteome of the nigrostriatal tissues in the presence or absence of minocycline, levodopa and manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP). The differentially expressed proteins were identified and proteome profiles were correlated with the pathological and biochemical anomalies induced by MPTP and maneb and paraquat. MPTP altered the expression of twelve while combined maneb and paraquat altered the expression of fourteen proteins. Minocycline, levodopa and MnTMPyP, respectively, restored the expression of three, seven and eight proteins in MPTP and seven, eight and eight proteins in maneb- and paraquat-treated groups. Although levodopa and MnTMPyP rescued from MPTP- and maneb- and paraquat-mediated increase in the microglial activation and decrease in manganese-superoxide dismutase expression and complex I activity, dopamine content and number of dopaminergic neurons, minocycline defended mainly against maneb- and paraquat-mediated alterations. The results demonstrate that MPTP and combined maneb and paraquat induce mitochondrial dysfunction and microglial activation and alter the expression of a bunch of mitochondrial proteins leading to the nigrostriatal dopaminergic neurodegeneration and minocycline, levodopa or MnTMPyP variably offset scores of such changes. © 2013 Elsevier B.V.
Nigrostriatal proteomics of cypermethrin-induced dopaminergic neurodegeneration: Microglial activation-dependent and -independent regulations
(2011) Anand Kumar Singh; Manindra Nath Tiwari; Anubhuti Dixit; Ghanshyam Upadhyay; Devendra Kumar Patel; Dhirendra Singh; Om Prakash; Mahendra Pratap Singh
The study aimed to identify the differentially expressed nigrostriatal proteins in cypermethrin-induced neurodegeneration and to investigate the role of microglial activation therein. Proteomic approaches were used to identify the differentially expressed proteins. Microglial activation, tyrosine hydroxylase immunoreactivity (TH-IR), dopamine content, and neurobehavioral changes were measured according to the standard procedures. The expressions of a-internexin intermediate filament (α-IIF), ATP synthase D chain (ATP-SD), heat shock protein (Hsp)-70, truncated connexin-47, Hsp-60, mitogen-activated protein kinaseactivated kinase-5, nicotinamide adenine dinucleotide dehydrogenase 24k chain precursor, platelet-activating factor acetyl hydrolase 1b-α2 (PAF-AH 1b-α2), and synaptosomal-associated protein-25 (SNAP-25) were altered in the substantia nigra and nicotinamide adenine dinucleotide- specific isocitrate dehydrogenase, phosphatidylethanolamine-binding protein-1, prohibitin, protein disulfide isomerase-endoplasmic reticulum 60 protease, stathmin, and ubiquitin-conjugating enzyme in the striatum along with motor impairment, decreased dopamine and TH-IR, and increased microglial activation after cypermethrin exposure. Minocycline restored α-IIF, ATP-SD chain, truncated connexin-47, Hsp-60, PAF-AH 1b-α2, stathmin and SNAP-25 expressions, motor impairment, dopamine, TH-IR, and microglial activation. The results suggest that cypermethrin produces microglial activation-dependent and -independent changes in the expression patterns of the nigrostriatal proteins leading to dopaminergic neurodegeneration. © The Author 2011. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Resveratrol potentiates cytochrome P450 2 d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse
(2012) Garima Srivastava; Anubhuti Dixit; Sharawan Yadav; Devendra Kumar Patel; Om Prakash; Mahendra Pratap Singh
A strong association between polymorphisms of the cytochrome P450 (CYP/Cyp) 2D6 gene and risk to Parkinson's disease (PD) is well established. The present study investigated the neuroprotective potential of Cyp2d22, a mouse ortholog of human CYP2D6, in maneb- and paraquat-induced parkinsonism and the mechanisms involved therein along with the effects of resveratrol on various parameters associated with Cyp2d22-mediated neuroprotection. The animals were treated intraperitoneally with resveratrol (10 mg/kg, daily) and paraquat (10 mg/kg) alone or in combination with maneb (30 mg/kg), twice a week, for 9 weeks, along with their respective controls. The subsets of animals were also treated intraperitoneally with a Cyp2d22 inhibitor, ketoconazole (100 mg/kg, daily). Maneb and paraquat reduced Cyp2d22 and vesicular monoamine transporter type 2 (VMAT-2) expressions, the number of tyrosine hydroxylase-positive cells, and dopamine content and increased paraquat accumulation in the nigrostriatal tissues, oxidative stress, microglial activation, neuroinflammation, and apoptosis. Cyp2d22 inhibitor significantly exacerbated all these neurodegenerative indexes. Resveratrol cotreatment, partially but significantly, ameliorated the neurodegenerative changes by altering Cyp2d22 expression and paraquat accumulation. The results obtained in the study demonstrate that Cyp2d22 offers neuroprotection in maneb- and paraquat-induced dopaminergic neurodegeneration and resveratrol enhances its neuroprotective credentials by influencing Cyp2d22 expression and paraquat accumulation. © 2012 Elsevier Inc. All rights reserved.
Rodent models and contemporary molecular techniques: Notable feats yet incomplete explanations of Parkinson's disease pathogenesis
(Humana Press Inc., 2012) Sharawan Yadav; Anubhuti Dixit; Sonal Agrawal; Ashish Singh; Garima Srivastava; Anand Kumar Singh; Pramod Kumar Srivastava; Om Prakash; Mahendra Pratap Singh
Rodent models and molecular tools, mainly omics and RNA interference, have been rigorously used to decode the intangible etiology and pathogenesis of Parkinson's disease (PD). Although convention of contemporary molecular techniques and multiple rodent models paved imperative leads in deciphering the role of putative causative factors and sequential events leading to PD, complete and clear-cut mechanisms of pathogenesis are still hard to pin down. The current article reviews the implications and pros and cons of rodent models and molecular tools in understanding the molecular and cellular bases of PD pathogenesis based on the existing literature. Probable rationales for short of comprehensive leads and future possibilities in spite of the extensive applications of molecular tools and rodent models have also been discussed. © Springer Science+Business Media, LLC 2012.
Tiny non-coding RNAs in Parkinson's disease: Implications, expectations and hypes
(Elsevier Ltd, 2011) Garima Srivastava; Anubhuti Dixit; Om Prakash; Mahendra Pratap Singh
Parkinson's disease (PD) is the second most prevalent, progressive and aging related neurodegenerative disorder, characterized by the irreversible and selective degeneration of the nigrostriatal dopaminergic neurons. The early diagnosis, molecular explanation and permanent cure of this devastating and baffling disease have not yet been completely deciphered. Tiny non-coding RNAs, which consist of small or short interfering RNA (siRNA) and micro RNA (miRNA), intervene with and silence the expression of the specific genes through the evolutionary conserved process of RNA interference and act as post-transcriptional regulators. The differential expression patterns of miRNAs operate as key watchdogs and facilitate the identification of the potential therapeutic targets; however, miRNA modifiers aid in designing the strategies to encounter PD. Similarly, siRNA-mediated gene silencing paves the way to understand the function of the specific genes in PD pathogenesis by knocking down their expression. Applications of siRNAs and contributions of the potential miRNAs in investigating the etiology and molecular mechanisms of PD as well as in therapeutic interventions have been discussed in this article. The review also highlights the achievements, expectations and hypes associated with these tiny non-coding RNAs in PD. © 2011 Elsevier B.V. All rights reserved.