The efficacy of systemic administration of lipopolysaccharide in modelling pre-motor Parkinson’s disease in C57BL/6 mice

Deng, Isaac; Wiese, Michael; Zhou, Xin‐Fu; Bobrovskaya, Larisa

doi:10.1016/j.neuro.2021.05.015

Cited by 8 publications

(9 citation statements)

References 55 publications

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“…Despite using a higher dose, contrary to the studies conducted by Pan-Montojo et al (2010, 2012, several studies reported a lack of asyn pathology development in the brain following oral rotenone treatment (Morais et al, 2018;Deng et al, 2021).…”

Section: Impact Of Aging In Body-first Pdmentioning

confidence: 85%

“…Importantly, this progressive pathology was prevented by hemi-vagotomy and partial sympathectomy implicating the direct role of the vagus and sympathetic nerves in the development of CNS pathology following rotenone treatment (Pan-Montojo et al, 2010 , 2012 ). Despite using a higher dose, contrary to the studies conducted by Pan-Montojo et al ( 2010 , 2012 ), several studies reported a lack of asyn pathology development in the brain following oral rotenone treatment (Morais et al, 2018 ; Deng et al, 2021 ). These studies propose to increase the treatment dose for more effective PD disease modeling (Deng et al, 2021 ).…”

Section: Impact Of Aging On Pathology and Neurodegenerationmentioning

confidence: 89%

“…Despite using a higher dose, contrary to the studies conducted by Pan-Montojo et al ( 2010 , 2012 ), several studies reported a lack of asyn pathology development in the brain following oral rotenone treatment (Morais et al, 2018 ; Deng et al, 2021 ). These studies propose to increase the treatment dose for more effective PD disease modeling (Deng et al, 2021 ). However, the young age of the animals used is more likely to be the limiting factor in modeling disease in these studies.…”

Section: Impact Of Aging On Pathology and Neurodegenerationmentioning

confidence: 89%

“…These studies propose to increase the treatment dose for more effective PD disease modeling (Deng et al, 2021). However, the young age of the animals used is more likely to be the limiting factor in modeling disease in these studies.…”

Section: Impact Of Aging In Body-first Pdmentioning

confidence: 99%

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Impact of aging on animal models of Parkinson's disease

Klæstrup

Just

Holm

et al. 2022

Front. Aging Neurosci.

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Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to explore the pathophysiology underlying neurodegeneration and the initiation and spread of alpha-synuclein-related PD pathology, and to investigate biomarkers and therapeutic strategies. However, bench-to-bedside translation of preclinical findings remains suboptimal and successful disease-modifying treatments remain to be discovered. Despite aging being the main risk factor for developing idiopathic PD, most studies employ young animals in their experimental set-up, hereby ignoring age-related cellular and molecular mechanisms at play. Consequently, studies in young animals may not be an accurate reflection of human PD, limiting translational outcomes. Recently, it has been shown that aged animals in PD research demonstrate a higher susceptibility to developing pathology and neurodegeneration, and present with a more disseminated and accelerated disease course, compared to young animals. Here we review recent advances in the investigation of the role of aging in preclinical PD research, including challenges related to aged animal models that are limiting widespread use. Overall, current findings indicate that the use of aged animals may be required to account for age-related interactions in PD pathophysiology. Thus, although the use of older animals has disadvantages, a model that better represents clinical disease within the elderly would be more beneficial in the long run, as it will increase translational value and minimize the risk of therapies failing during clinical studies. Furthermore, we provide recommendations to manage the challenges related to aged animal models.

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Section: Impact Of Aging In Body-first Pdmentioning

confidence: 85%

Section: Impact Of Aging On Pathology and Neurodegenerationmentioning

confidence: 89%

Section: Impact Of Aging On Pathology and Neurodegenerationmentioning

confidence: 89%

Section: Impact Of Aging In Body-first Pdmentioning

confidence: 99%

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Impact of aging on animal models of Parkinson's disease

Klæstrup

Just

Holm

et al. 2022

Front. Aging Neurosci.

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“…In the present study, we wished to further explore the mechanisms underlying the anti-inflammatory activity of COL-3 towards brain microglial cells, using its parent compound DOX as a reference tetracycline molecule. For this research project, we used brain microglial cells challenged with LPS and amyloid aggregates of the synaptic protein αSa in order to model brain inflammatory-type reactions as they may occur in PD neurodegeneration [23][24][25]. We found that COL-3 was intrinsically more potent than DOX, as it was optimally effective at lower concentrations than its parent compound.…”

Section: Introductionmentioning

confidence: 99%

The Chemically-Modified Tetracycline COL-3 and Its Parent Compound Doxycycline Prevent Microglial Inflammatory Responses by Reducing Glucose-Mediated Oxidative Stress

Ferreira

Pereira

Francis

et al. 2021

Cells

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We used mouse microglial cells in culture activated by lipopolysaccharide (LPS) or α-synuclein amyloid aggregates (αSa) to study the anti-inflammatory effects of COL-3, a tetracycline derivative without antimicrobial activity. Under LPS or αSa stimulation, COL-3 (10, 20 µM) efficiently repressed the induction of the microglial activation marker protein Iba-1 and the stimulated-release of the pro-inflammatory cytokine TNF-α. COL-3′s inhibitory effects on TNF-α were reproduced by the tetracycline antibiotic doxycycline (DOX; 50 µM), the glucocorticoid dexamethasone, and apocynin (APO), an inhibitor of the superoxide-producing enzyme NADPH oxidase. This last observation suggested that COL-3 and DOX might also operate themselves by restraining oxidative stress-mediated signaling events. Quantitative measurement of intracellular reactive oxygen species (ROS) levels revealed that COL-3 and DOX were indeed as effective as APO in reducing oxidative stress and TNF-α release in activated microglia. ROS inhibition with COL-3 or DOX occurred together with a reduction of microglial glucose accumulation and NADPH synthesis. This suggested that COL-3 and DOX might reduce microglial oxidative burst activity by limiting the glucose-dependent synthesis of NADPH, the requisite substrate for NADPH oxidase. Coherent with this possibility, the glycolysis inhibitor 2-deoxy-D-glucose reproduced the immunosuppressive action of COL-3 and DOX in activated microglia. Overall, we propose that COL-3 and its parent compound DOX exert anti-inflammatory effects in microglial cells by inhibiting glucose-dependent ROS production. These effects might be strengthened by the intrinsic antioxidant properties of DOX and COL-3 in a self-reinforcing manner.

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Investigating affective neuropsychiatric symptoms in rodent models of Parkinson’s disease

Boi,

Fisone

2024

International Review of Neurobiology

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The efficacy of systemic administration of lipopolysaccharide in modelling pre-motor Parkinson’s disease in C57BL/6 mice

Cited by 8 publications

References 55 publications

Impact of aging on animal models of Parkinson's disease

Impact of aging on animal models of Parkinson's disease

The Chemically-Modified Tetracycline COL-3 and Its Parent Compound Doxycycline Prevent Microglial Inflammatory Responses by Reducing Glucose-Mediated Oxidative Stress

Investigating affective neuropsychiatric symptoms in rodent models of Parkinson’s disease

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