The impact of 1MeTIQ on the dopaminergic system function in the 6-OHDA model of Parkinson’s disease

Wąsik, Agnieszka; Polak, Dawid; Romańska, Irena; Michaluk, Jerzy; Antkiewicz-Michaluk, Lucyna

doi:10.1016/j.pharep.2016.08.004

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…The accumulation of these factors further resulted in the progressive loss of DA neurons. It was interesting to note that ICA produced neuroprotection against DA neurotoxicity induced by LPS and 6-OHDA, two toxins with different modes of functions ( Badshah et al, 2016 ; Wasik et al, 2016 ). 6-OHDA was a hydroxyl derivative of DA and competed for DA uptake sites and undergoes auto-oxidation, leading to direct DA neuronal damage by producing neurotoxic substances ( Im et al, 2016 ; Song et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro

Wang

Huang

et al. 2018

Front. Mol. Neurosci.

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Parkinson’s disease (PD) is one of the most common neurodegenerative diseases characterized with a gradual loss of midbrain substantia nigra (SN) dopamine (DA) neurons. An excessive evidence demonstrated that microglia-mediated inflammation might be involved in the pathogenesis of PD. Thus, inhibition of neuroinflammation might possess a promising potential for PD treatment. Icariin (ICA), a single active component extracted from the Herba Epimedii, presents amounts of pharmacological properties, such as anti-inflammation, anti-oxidant, and anti-aging. Recent studies show ICA produced neuroprotection against brain dysfunction. However, the mechanisms underlying ICA-exerted neuroprotection are fully illuminated. In the present study, two different neurotoxins of 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS)-induced rat midbrain DA neuronal damage were applied to investigate the neuroprotective effects of ICA. In addition, primary rat midbrain neuron-glia co-cultures were performed to explore the mechanisms underlying ICA-mediated DA neuroprotection. In vitro data showed that ICA protected DA neurons from LPS/6-OHDA-induced DA neuronal damage and inhibited microglia activation and pro-inflammatory factors production via the suppression of nuclear factor-κB (NF-κB) pathway activation. In animal results, ICA significantly reduced microglia activation and significantly attenuated LPS/6-OHDA-induced DA neuronal loss and subsequent animal behavior changes. Together, ICA could protect DA neurons against LPS- and 6-OHDA-induced neurotoxicity both in vivo and in vitro. These actions might be closely associated with the inhibition of microglia-mediated neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro

Wang

Huang

et al. 2018

Front. Mol. Neurosci.

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“…When administered intraperitoneally, 1MeTIQ can easily passed through the blood-brain barrier and concentrates in the brain (Kikuchi et al 1991 ). As previously demonstrated by our team, 1MeTIQ displays neuroprotective activity both in vitro (Antkiewicz-Michaluk et al 2006 ) and in vivo in several animal models of PD (Antkiewicz-Michaluk et al 2003 , 2004 , 2014 ; Wąsik et al 2016a , b , 2017 ). Our earlier experimental studies determined that 1MeTIQ acts as a reversible MAO (monoamine oxidase) inhibitor and blocks the MAO-dependent oxidative pathway with the simultaneous activation of the COMT (catechol-O-methyltransferase)-dependent O-methylation catabolic pathway.…”

Section: Introductionsupporting

confidence: 62%

The Protective Effect of Repeated 1MeTIQ Administration on the Lactacystin-Induced Impairment of Dopamine Release and Decline in TH Level in the Rat Brain

et al. 2018

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Parkinson’s disease (PD) is a neurodegenerative disorder of the central nervous system (CNS) caused by a progressive loss of nigrostriatal dopaminergic neurons. Dysfunction of the ubiquitin-proteasome system (UPS) plays an important role in the pathogenesis of PD. Intranigral administration of the UPS inhibitor lactacystin is used to obtain a valuable animal model for investigating putative neuroprotective treatments for PD. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous amine that displays neuroprotective properties. This compound acts as a reversible monoamine oxidase (MAO) inhibitor and a natural free radical scavenger. In the present experiment, we investigated the effect of acute and chronic treatment with 1MeTIQ on locomotor activity and the release of dopamine as well as its metabolites in the striatum of unilaterally lactacystin-lesioned and sham-operated rats using in vivo microdialysis. Additionally, changes in the level of tyrosine hydroxylase (TH) in the substantia nigra were measured. Unilateral lactacystin injection into the substantia nigra caused significant impairment of dopamine release (approx. 45%) and a marked decline in the TH level. These effects were completely antagonized by multiple treatments with 1MeTIQ. The results obtained from the in vivo microdialysis study as well as from the ex vivo experiments suggest that multiple administration of 1MeTIQ protects dopaminergic neurons against the lactacystin-induced decline in TH concentration in the substantia nigra and prevents disturbances of dopamine release in the striatum. We have demonstrated that 1MeTIQ is capable of maintaining the physiological functions of the striatal dopamine neurons damaged by unilateral lactacystin lesion.

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“…Its neurotoxicity involves the accumulation of toxin in the catecholaminergic neurons triggering the alteration of the cellular homeostasis and neuronal damages. 6-OHDA oxidation by MAO-A generates H 2 O 2 which, besides being highly cytotoxic, triggers the production of oxygen radicals [ 77 – 79 ]. Another model included the alteration of dopaminergic neurotransmission by drugs, such as reserpine [ 80 ], or by genetic manipulation to study the progression of dopaminergic cell degeneration and motor signs [ 81 ].…”

Section: Resultsmentioning

confidence: 99%

Flavonoids as Therapeutic Agents in Alzheimer’s and Parkinson’s Diseases: A Systematic Review of Preclinical Evidences

Teles

Diniz

Pinto

et al. 2018

Oxidative Medicine and Cellular Longevity

166

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Alzheimer's and Parkinson's diseases are considered the most common neurodegenerative disorders, representing a major focus of neuroscience research to understanding the cellular alterations and pathophysiological mechanisms involved. Several natural products, including flavonoids, are considered able to cross the blood-brain barrier and are known for their central nervous system-related activity. Therefore, studies are being conducted with these chemical constituents to analyze their activities in slowing down the progression of neurodegenerative diseases. The present systematic review summarizes the pharmacological effects of flavonoids in animal models for Alzheimer's and Parkinson's diseases. A PRISMA model for systematic review was utilized for this search. The research was conducted in the following databases: PubMed, Web of Science, BIREME, and Science Direct. Based on the inclusion criteria, 31 articles were selected and discussed in this review. The studies listed revealed that the main targets of action for Alzheimer's disease therapy were reduction of reactive oxygen species and amyloid beta-protein production, while for Parkinson's disease reduction of the cellular oxidative potential and the activation of mechanisms of neuronal death. Results showed that a variety of flavonoids is being studied and can be promising for the development of new drugs to treat neurodegenerative diseases. Moreover, it was possible to verify that there is a lack of translational research and clinical evidence of these promising compounds.

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The impact of 1MeTIQ on the dopaminergic system function in the 6-OHDA model of Parkinson’s disease

Cited by 8 publications

References 27 publications

RETRACTED: Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro

RETRACTED: Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro

The Protective Effect of Repeated 1MeTIQ Administration on the Lactacystin-Induced Impairment of Dopamine Release and Decline in TH Level in the Rat Brain

Flavonoids as Therapeutic Agents in Alzheimer’s and Parkinson’s Diseases: A Systematic Review of Preclinical Evidences

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