Early Postnatal Exposure to Paraquat and Maneb in Mice Increases Nigrostriatal Dopaminergic Susceptibility to a Re-challenge with the Same Pesticides at Adulthood: Implications for Parkinson’s Disease

Colle, Dirleise; Santos, Danúbia Bonfanti; Naime, Aline Aita; Gonçalves, Cinara L.; Ghizoni, Heloisa; Hort, Mariana Appel; Farina, Marcelo

doi:10.1007/s12640-019-00097-9

Cited by 22 publications

(16 citation statements)

References 86 publications

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“…Behavioral assessments revealed that prenatal exposure to PQ resulted in motor deficits resembling akinesia in rat offspring, consistent with previous studies indicating PQ-induced motor incoordination and reduced spontaneous motor behavior due to degeneration of the nigrostriatal dopaminergic system (Li et al, 2005 ; Colle et al, 2020 ). Interestingly, the administration of AU significantly mitigated these motor deficits caused by PQ, suggesting a positive effect on motor function.…”

Section: Discussionsupporting

confidence: 89%

Bioactive strawberry fruit (Arbutus unedo L.) extract remedies paraquat-induced neurotoxicity in the offspring prenatally exposed rats

Ait Lhaj,

Ibork,

El Idrissi

et al. 2023

Front. Neurosci.

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BackgroundParaquat (1,1′-dimethyl-4-4′-bipyridinium dichloride) exposure is well-established as a neurotoxic agent capable of causing neurological deficits in offspring. This study aimed to investigate therapeutic effects of Arbutus unedo L. aqueous extract (AU) against paraquat (PQ) exposure.MethodsFor that the phytoconstituents of AU was determined by LC/MS, and then its antioxidant potential was assessed by DPPH and ABTS assays. The assessment included its impact on cell viability and mitochondrial metabolism using N27 dopaminergic cells. Additionally, we evaluated the effects of prenatal PQ exposure on motor coordination, dopamine levels, trace element levels, and total antioxidant capacity (TAC) in rat progeny.ResultsThe phytochemical profile of AU extract revealed the presence of 35 compounds, primarily phenolic and organic acids, and flavonoids. This accounted for its strong in vitro antioxidant activities against DPPH and ABTS radicals, surpassing the activities of vitamin C. Our findings demonstrated that AU effectively inhibited PQ-induced loss of N27 rat dopaminergic neural cells and significantly enhanced their mitochondrial respiration. Furthermore, daily post-treatment with AU during the 21 days of the rat's pregnancy alleviated PQ-induced motor deficits and akinesia in rat progeny. These effects inhibited dopamine depletion and reduced iron levels in the striatal tissues. The observed outcomes appeared to be mediated by the robust antioxidant activity of AU, effectively counteracting the PQ-induced decrease in TAC in the blood plasma of rat progeny. These effects could be attributed to the bioactive compounds present in AU, including phenolic acids such as gallic acid and flavonoids such as quercetin, rutin, apigenin, glucuronide, and kaempferol, all known for their potent antioxidant capacity.DiscussionIn conclusion, this preclinical study provided the first evidence of the therapeutic potential of AU extract against PQ-induced neurotoxicity. These findings emphasize the need for further exploration of the clinical applicability of AU in mitigating neurotoxin-induced brain damage.

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Section: Discussionsupporting

confidence: 89%

Bioactive strawberry fruit (Arbutus unedo L.) extract remedies paraquat-induced neurotoxicity in the offspring prenatally exposed rats

Ait Lhaj,

Ibork,

El Idrissi

et al. 2023

Front. Neurosci.

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“…Alternatively, prenatal exposure to buprenorphine may render the offspring vulnerable to undergoing pathological processes with subsequent insults later in life as a result of perturbed immune machinery that was epigenetically modified during the most sensitive period of the immune system establishment. Similarly, a hypothesis has been developed that prenatal exposure to particular substances predisposes neonates to certain diseases, such as Parkinson's disease and autoimmune disease [41,42]. This notion is also echoed by our findings that prenatal exposure to buprenorphine not only elevates basal levels of oxidative stress but also potentiates LPS-stimulated oxidative stress in primary astrocytes.…”

Section: Discussionsupporting

confidence: 78%

Dextromethorphan Dampens Neonatal Astrocyte Activation and Endoplasmic Reticulum Stress Induced by Prenatal Exposure to Buprenorphine

Lin

Tao

Tsay³

et al. 2021

Behavioural Neurology

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Prenatal exposure to buprenorphine renders offspring vulnerable to cerebral impairments. In this study, our data demonstrate, for the first time, that prenatal exposure to buprenorphine escalates astrocyte activation concurrent with indications of endoplasmic reticulum (ER) stress in the hippocampi of neonates, and this can be prevented by the coadministration of dextromethorphan with buprenorphine. Furthermore, dextromethorphan can inhibit the accumulation of GPR37 in the hippocampus of newborns caused by buprenorphine and is accompanied by the proapoptotic ER stress response that involves the procaspase-3/CHOP pathway. Primary astrocyte cultures derived from the neonates of the buprenorphine group also displayed aberrant ER calcium mobilization and elevated basal levels of cyclooxygenase-2 (COX-2) at 14 days in vitro while showing sensitivity to lipopolysaccharide-activated expression of COX-2. Similarly, these long-lasting defects in the hippocampus and astrocytes were abolished by dextromethorphan. Our findings suggest that prenatal exposure to buprenorphine might instigate long-lasting effects on hippocampal and astrocytic functions. The beneficial effects of prenatal coadministration of dextromethorphan might be, at least in part, attributed to its properties in attenuating astrocyte activation and hippocampal ER stress in neonates.

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“…Parkinson's disease (PD) is an aging neurologic disease where environmental exposure during prenatal or early developmental period may be risk factors that have a longterm or an extended latency for PD's pathogenesis in an individual's later adult life. A possible explanation can be that the decreased population of nigrostriatal dopamine (DA) cell bodies early in life of an individual due to negative environmental exposure may speed up the DA system to reach decreased levels of DA cell bodies associated with PD when combined with normal agingrelated loss of the cell bodies later in life [198][199][200]. It is also possible that the neuronal damage in early development may make an individual more vulnerable to subsequent environmental risk factors to result in PD that may not have occurred without the prior developmental exposure.…”

Section: 2ii Parkinson's Diseasementioning

confidence: 99%

Extracellular Vesicles in Premature Aging and Diseases in Adulthood Due to Developmental Exposures

Pinson¹,

Chung²,

Adams³

et al. 2021

Aging and disease

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The developmental origins of health and disease (DOHaD) is a paradigm that links prenatal and early life exposures that occur during crucial periods of development to health outcome and risk of disease later in life. Maternal exposures to stress, some psychoactive drugs and alcohol, and environmental chemicals, among others, may result in functional changes in developing fetal tissues, creating a predisposition for disease in the individual as they age. Extracellular vesicles (EVs) may be mediators of both the immediate effects of exposure during development and early childhood as well as the long-term consequences of exposure that lead to increased risk and disease severity later in life. Given the prevalence of diseases with developmental origins, such as cardiovascular disease, neurodegenerative disorders, osteoporosis, metabolic dysfunction, and cancer, it is important to identify persistent mediators of disease risk. In this review, we take this approach, viewing diseases typically associated with aging in light of early life exposures and discuss the potential role of EVs as mediators of lasting consequences.

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Early Postnatal Exposure to Paraquat and Maneb in Mice Increases Nigrostriatal Dopaminergic Susceptibility to a Re-challenge with the Same Pesticides at Adulthood: Implications for Parkinson’s Disease

Cited by 22 publications

References 86 publications

Bioactive strawberry fruit (Arbutus unedo L.) extract remedies paraquat-induced neurotoxicity in the offspring prenatally exposed rats

Bioactive strawberry fruit (Arbutus unedo L.) extract remedies paraquat-induced neurotoxicity in the offspring prenatally exposed rats

Dextromethorphan Dampens Neonatal Astrocyte Activation and Endoplasmic Reticulum Stress Induced by Prenatal Exposure to Buprenorphine

Extracellular Vesicles in Premature Aging and Diseases in Adulthood Due to Developmental Exposures

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