Neurotoxin-Induced Rodent Models of Parkinson’s Disease: Benefits and Drawbacks

El‐Gamal, Mohammed I.; Salama, Mohamed; Collins-Praino, Lyndsey E.; Baetu, Irina; Fathalla, Ahmed; Soliman, Amira; Mohamed, Wael; Moustafa, Ahmed A.

doi:10.1007/s12640-021-00356-8

Cited by 28 publications

(17 citation statements)

References 272 publications

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“…MPP+ released from astrocytes into the extracellular space is taken up by neighboring DAergic neurons. It consequently becomes highly concentrated in the microglia and induces oxidative stress and decreased adenosine triphosphate (ATP) generation by inhibiting mitochondrial complex I of the mitochondrial electron transport chain ( El-Gamal et al, 2021 ). This leads to apoptosis and necrosis of DAergic neurons due to the rapid decrease in the concentration of ATP in the SN and striatum.…”

Section: Neurotoxin-induced Experimental Models Of Cognitive Impairmentmentioning

confidence: 99%

Experimental Models of Cognitive Impairment for Use in Parkinson’s Disease Research: The Distance Between Reality and Ideal

Fan

Han

Zhao

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is the second most common neurodegenerative disease. Cognitive impairment is one of the key non-motor symptoms of PD, affecting both mortality and quality of life. However, there are few experimental studies on the pathology and treatments of PD with mild cognitive impairment (PD-MCI) and PD dementia (PDD) due to the lack of representative models. To identify new strategies for developing representative models, we systematically summarized previous studies on PD-MCI and PDD and compared differences between existing models and diseases. Our initial search identified 5432 articles, of which 738 were duplicates. A total of 227 articles met our inclusion criteria and were included in the analysis. Models fell into three categories based on model design: neurotoxin-induced, transgenic, and combined. Although the neurotoxin-induced experimental model was the most common type that was used during every time period, transgenic and combined experimental models have gained significant recent attention. Unfortunately, there remains a big gap between ideal and actual experimental models. While each model has its own disadvantages, there have been tremendous advances in the development of PD models of cognitive impairment, and almost every model can verify a hypothesis about PD-MCI or PDD. Finally, our proposed strategies for developing novel models are as follows: a set of plans that integrate symptoms, biochemistry, neuroimaging, and other objective indicators to judge and identify that the novel model plays a key role in new strategies for developing representative models; novel models should simulate different clinical features of PD-MCI or PDD; inducible α-Syn overexpression and SH-SY5Y-A53T cellular models are good candidate models of PD-MCI or PDD.

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Section: Neurotoxin-induced Experimental Models Of Cognitive Impairmentmentioning

confidence: 99%

Experimental Models of Cognitive Impairment for Use in Parkinson’s Disease Research: The Distance Between Reality and Ideal

Fan

Han

Zhao

et al. 2021

Front. Aging Neurosci.

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“…Hence, models of PD have invariably utilized chemical neurotoxins that trigger damage to the SNpc, reduce dopamine levels, induce mitochondrial damage, redox stress, and neuroinflammation, and thereby reproduce many of the elements of PD pathology. Commonly used chemical neurotoxins include rotenone, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), and paraquat [ 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…Rotenone is an agricultural pesticide that can cross the blood-brain barrier (BBB) and enter dopaminergic neurons independently of DA transporters and inhibits mitochondrial complex I and associated ATP production via the coupling of the electron transport chain to oxidative phosphorylation. Rotenone also generates redox stress and can induce α-synuclein positive aggregations [ 20 , 21 , 22 ]. MPTP can cross the BBB where it is metabolized by monoamine oxidase-B (MAO-B) in astrocytes into the potent neurotoxin, 1-methyl-4-phenylpyridimium (MPP+), which behaves as a structural analogue to dopamine and enters dopaminergic neurons via DA transporters.…”

Section: Introductionmentioning

confidence: 99%

“…MPTP can cross the BBB where it is metabolized by monoamine oxidase-B (MAO-B) in astrocytes into the potent neurotoxin, 1-methyl-4-phenylpyridimium (MPP+), which behaves as a structural analogue to dopamine and enters dopaminergic neurons via DA transporters. MPP+ is also a mitochondrial inhibitor and can trigger cellular redox stress [ 20 , 21 , 22 ]. 6-OHDA is a dopamine analogue with a high affinity for dopamine transporters but without BBB penetrance.…”

Section: Introductionmentioning

confidence: 99%

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The Neuroprotective Effects of Cannabis-Derived Phytocannabinoids and Resveratrol in Parkinson’s Disease: A Systematic Literature Review of Pre-Clinical Studies

Prakash

Carter

2021

Brain Sciences

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Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed, and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.

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“…Similar reports exist for Alzheimer's disease as well [ [11] , [12] , [13] ]. Indeed pesticide-induced animal models of Parkinson's disease and Alzheimer's disease recapitulate many of the pathologies seen in human patients and have become popular models to study [ 12 , 14 ]. However, the specific effect of pesticides at the cellular and molecular levels is yet to be fully established.…”

Section: Introductionmentioning

confidence: 99%

Pesticides DEET, fipronil and maneb induce stress granule assembly and translation arrest in neuronal cells

Bhadauriya¹,

Parihar²,

Ganesh³

2021

Biochemistry and Biophysics Reports

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Pesticides entering our body, either directly or indirectly, are known to increase the risk of developing neurodegenerative disorders. The pesticide-induced animal models of Parkinson's disease and Alzheimer's disease recapitulates many of the pathologies seen in human patients and have become popular models for studying disease biology. However, the specific effect of pesticides at the cellular and molecular levels is yet to be fully established. Here we investigated the cellular effect of three commonly used pesticides: DEET, fipronil and maneb. Specifically, we looked at the effect of these pesticides in the formation of stress granules and the concomitant translational arrest in a neuronal cell line. Stress granules represent an ensemble of non-translating mRNAs and appear in cells under physiological stress. Growing evidence indicates that chronic stress may covert the transient stress granules into amyloids and may thus induce neurodegeneration. We demonstrate here that all three pesticides tested induce stress granules and translation arrest through the inactivation of the eukaryotic initiation factor, eIF2α. We also show that oxidative stress could be one of the major intermediary factors in the pesticide-induced stress granule formation and that it is a reversible process. Our results suggest that prolonged pesticide exposure may result in long-lived stress granules, thus compromising the neuronal stress response pathway and leading to neurodegeneration.

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Neurotoxin-Induced Rodent Models of Parkinson’s Disease: Benefits and Drawbacks

Cited by 28 publications

References 272 publications

Experimental Models of Cognitive Impairment for Use in Parkinson’s Disease Research: The Distance Between Reality and Ideal

Experimental Models of Cognitive Impairment for Use in Parkinson’s Disease Research: The Distance Between Reality and Ideal

The Neuroprotective Effects of Cannabis-Derived Phytocannabinoids and Resveratrol in Parkinson’s Disease: A Systematic Literature Review of Pre-Clinical Studies

Pesticides DEET, fipronil and maneb induce stress granule assembly and translation arrest in neuronal cells

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