Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine

Barbiero, Janaína K.; Santiago, Ronise Martins; Persike, Daniele Suzete; Fernandes, Maria José da Silva; Tonin, Fernanda S.; Cunha, Cláudio Da; Boschen, Suelen Lúcio; Lima, Marcelo M.S.; Vital, Maria A.B.F.

doi:10.1016/j.bbr.2014.08.014

Cited by 78 publications

(52 citation statements)

References 66 publications

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“…PPAR-α agonist fenofibrate and palmitoylethanolamide could prevent DA cell death in the SNpc, attenuate the loss of TH immunoreactivity in the striatum, and reverse motor deficits by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [56,57] or 6-hydroxydopamine (6-OHDA) [58]. PPAR-α agonist fenofibrate, PPAR-γ agonist pioglitazone, and PPAR-α/γ dual agonist 2-[4-(5-chlorobenzo [d] thiazol-2-yl) phenoxy]-2-methylpropanoic acid (MHY908) could also protect against DA neuronal loss, motor deficit, depression-like behavior, and the impairment of learning and memory caused by MPTP [59][60][61]. PPAR-β/δ is expressed in the nuclei of DA neurons and in astrocytes.…”

Section: Discussionmentioning

confidence: 99%

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

Kao

Wei

Tsai

et al. 2019

IJMS

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Although several epidemiologic and animal studies have revealed correlations between obesity and neurodegenerative disorders, such as Parkinson disease (PD), the underlying pathological mechanisms of obesity-induced PD remain unclear. Our study aimed to assess the effect of diet-induced obesity on the brain dopaminergic pathway. For five months, starting from weaning, we gave C57BL/6 mice a high-fat diet (HFD) to generate an obese mouse model and investigate whether the diet reprogrammed the midbrain dopaminergic system. Tyrosine hydroxylase staining showed that the HFD resulted in fewer dopaminergic neurons in the substantia nigra (SN), but not the striatum. It also induced neuroinflammation, with increased astrogliosis in the SN and striatum. Dendritic spine density in the SN of HFD-exposed mice decreased, which suggested that prolonged HFD altered dopaminergic neuroplasticity. All three peroxisome proliferator-activated receptor (PPAR) subtype (PPAR-α, PPAR-β/δ, PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area of HFD mice when compared to those in controls. This study showed that a prolonged HFD induced neuroinflammation, suppressed PPAR levels, caused degeneration of midbrain dopaminergic neurons, and resulted in symptoms reminiscent of human PD. To our knowledge, this is the first study documenting the effects of an HFD on PPARs in dopaminergic neurons.

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Section: Discussionmentioning

confidence: 99%

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

Kao

Wei

Tsai

et al. 2019

IJMS

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“…MPTP treatment has been shown to activate caspase-3, resulting in apoptosis-associated neuronal death. On the other hand, treatment with neuroprotective drugs has been shown to inhibit caspase-3 activity and reduce neuronal damage [5] . PGT has been shown to be neuroprotective against decreased locomotion and rearing frequencies and to reverse hypolocomotion following intranigral infusion of MPTP.…”

Section: Discussionmentioning

confidence: 99%

“…Pioglitazone (PGT), a member of this group, is thought to have neuronprotective property through several mechanisms by increasing the gene transcription with the agonistic effect of PPARγ. However, it is not known whether it has a protective effect against neuronal damage in acute and long-term use [5] . PGT is known to have antidiabetic and adverse effects on the heart [6,7] .…”

Section: Introductionmentioning

confidence: 99%

Pioglitazonun NB2a Fare Nöroblastoma Hücre Kültürüdeki Nöroprotektif Etkisi

Vural¹,

Seyrek²

2018

Kafkas Univ Vet Fak Derg

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How to Cite This ArticleVural K, Seyrek O: The neuroprotective effect of pioglitazone on NB2a mouse neuroblastoma cell culture. AbstractPioglitazone (PGT) is a PPAR-γ activator that has neuroprotective properties via different mechanisms. It is thought to be neuroprotective in both acute and chronic use. Chlorpyrifos (CPS) is an Organophosphate insecticide that leads to attention deficit and cognitive problems in children and its neurotoxic effects are well known. This study aims to investigate the neuroprotective effects of PGT on CPS neurotoxicity in NB2a cell in the culture medium. We investigated the cell viability and proliferation using MTT assay and the percentage of neurite inhibition was analysed by measuring neurite outgrowth. Apoptosis was evaluated using the apoptotic index in TUNEL staining. Cell proliferation was found to be significantly reduced by CPS (25 µM), and this concentration-based reduction was prevented by PGT. Neurite outgrowth was inhibited by CPS (25 µM), whereas PGT significantly reversed neurite inhibition at and above 10 μM concentrations. The apoptotic index, which was increased using CPS (25 µM), was observed to reduce using PGT, depending on the concentration. Organophosphate is harmful to human health, and to our knowledge, there is no treatment. In individuals exposed to chlorpyrifos toxicity, acute toxic effects on neurons may be prevented or treated by PGT. ÖzPioglitazon (PGT), farklı mekanizmalar yoluyla nöroprotektif özelliklere sahip bir PPAR-γ aktivatörüdür. PGT akut ve kronik kullanımının nöroprotektif olduğu düşünülmektedir. Klorpirifos (CPS) çocuklarda dikkat eksikliği ve bilişsel problemlere yol açan bir organofosfat insektisit olup nörotoksik etkileri iyi bilinmektedir. Bu çalışmada, kültür ortamında fare kaynaklı NB2a kanser dizin hücrelerinde CPS nörotoksisitesi üzerine PGT'nin nöroprotektif etkileri olup olmadığının araştırdık. MTT analizini kullanarak hücre proliferasyonu üzerine etkilerini ve ılımlı nörotoksik etkinin bir göstergesi olan Nörotoksisite Tarama Testi ile % nörit inhibisyonu incelendi. Apopitoz, TUNEL boyamada apopitotik indeks kullanılarak değerlendirildi. CPS (25 μM) konsantrasyonda uygulandığında NB2a hücre proliferasyonu azalttı. PGT ise konsantrasyon bağlı olarak klorpirosa bağlı azalmayı önlendi. Klorpirifon 25 μM konsantrasyonda tama yakın Nörit uzamasını inhibe ederken, PGT 10 μM ve üzerindeki konsantrasyonlarda nörit inhibisyonunu önemli ölçüde engelledi. CFS (25 μM) ile artan apopitotik hücre sayısını, PGT 10 uM konsantarasyondan itibaren anlamlı düzeyde azalttığı görüldü. Organofosfatlar insan sağlığına zararlıdır ve toksik etkilerini önlemek için bildiğimiz bir tedavisi yoktur. Klorpirifos toksisitesine maruz kalan bireylerde, nöronlar üzerindeki akut toksik etkileri PGT ile önlenebilir veya tedavi edilebilir.

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“…In addition to its action of PPAR-γ, it has also been shown to bind to mitoNEET, a protein affiliated with the outer mitochondrial membrane, and it is argued that the mechanism of action for pioglitazone may extend beyond PPARγ [237]. Due to its effects on cellular metabolism, pioglitazone was examined in preclinical PD models and shown to be neuroprotective [238, 239]. A Phase II randomized, controlled trial of pioglitazone has recently been completed (clinicaltrials.gov ID NCT01280123).…”

Section: Mitochondrial Medicine and Alzheimer’s Diseasementioning

confidence: 99%

New Therapeutics to Modulate Mitochondrial Function in Neurodegenerative Disorders

Wilkins

Morris

2017

CPD

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Background Mitochondrial function and energy metabolism are impaired in neurodegenerative diseases. There is evidence for these functional declines both within the brain and systemically in Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. Due to these observations, therapeutics targeted to alter mitochondrial function and energy pathways are increasingly studied in pre-clinical and clinical settings. Methods The goal of this article was to review therapies with specific implications on mitochondrial energy metabolism published through May 2016 that have been tested for treatment of neurodegenerative diseases. Results We discuss implications for mitochondrial dysfunction in neurodegenerative diseases and how this drives new therapeutic initiatives. Conclusion: Thus far, treatments have achieved varying degrees of success. Further investigation into the mechanisms driving mitochondrial dysfunction and bioenergetic failure in neurodegenerative diseases is warranted.

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Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine

Cited by 78 publications

References 66 publications

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

Pioglitazonun NB2a Fare Nöroblastoma Hücre Kültürüdeki Nöroprotektif Etkisi

New Therapeutics to Modulate Mitochondrial Function in Neurodegenerative Disorders

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