Protective effect of hesperidin in a model of Parkinson's disease induced by 6-hydroxydopamine in aged mice

Background/Aims: The study aimed to investigate the protective effect of curcumin against oxidative stress-induced injury of Parkinson’s disease (PD) through the Wnt/β-catenin signaling pathway in rats. Methods: The successfully established PD rat models and normal healthy rats were randomly assigned into the 6-hydroxydopamine (6-OHDA), the curcumin (Cur) and the control groups. Immunohistochemistry was used to detect the positive expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and glial fibrillary acidic protein (GFAP). Deutocerebrum primary cells were extracted and classified into the control, 6-OHDA, Cur (5, 10, 15 µmol/L), Dickkopf-1 (DKK-1) and Cur + DKK-1 groups. MTT assays, adhesion tests and TUNEL staining were used to assess cell viability, adhesion and apoptosis, respectively. Western blotting and qRT-PCR were used to examine the protein and mRNA expressions of Wnt3a and β-catenin and the c-myc and cyclinD1 mRNA expressions. Results: TH and DAT expressions in the Cur group were elevated and GFAP was reduced compared with the 6-OHDA group. Curcumin enhanced viability, survival and adhesion and attenuated apoptosis of deutocerebrum primary cells by activating the Wnt/β-catenin signaling pathway. Higher Wnt3a and β-catenin mRNA and protein expressions and c-myc and cyclinD1 mRNA expressions, enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) contents, decreased malondialdehyde (MDA) content and elevated mitochondrial membrane potential (∆ψm) were found in the 10 and 15 µmol/L Cur groups compared with the 6-OHDA group. However, opposite tendencies were found in the Cur + DKK-1 group compared to the 10 µmol/L Cur group. Conclusion: This study suggests that curcumin could protect against oxidative stress-induced injury in PD rats via the Wnt/β-catenin signaling pathway.

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Protective effect of chlorogenic acid in an experimental model of Parkinson’s disease induced by 6-hydroxydopamine in rats

Journal of Shahid Sadoughi University of Medical Sciences ◽

10.18502/ssu.v27i1.869 ◽

2019 ◽

Author(s):

Dehnad Dehnad ◽

Zahra Kiasalari ◽

Mehrdad Roghani

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protective Effect ◽

Chlorogenic Acid ◽

Experimental Model ◽

Dopaminergic Neurons ◽

Male Rats ◽

Lesion Group ◽

Stereotaxic Surgery ◽

6 Hydroxydopamine

Introdution: Parkinson's disease is the second most common neurodegenerative disease. Considering the antioxidant and neuroprotective properties of chlorogenic acid, the purpose of this study was to evaluate the neuroprotective effect of this substance in an experimental model of Parkinson's disease. Methods: In this experimental study, Wisar male rats (n = 32) were divided into 4 groups: sham, chlorogenic acid-treated sham, lesion and chlorogenic-acid-treated lesion. The experimental model of Parkinson's disease was made by injecting 12.5 microgram of 6-hydroxydopamine dissolved in a saline-ascorbate solution into the left side of neostriatum. The chlorogenic acid-treated sham and the chlorogenic-acid-treated lesion groups received 10 mg/kg of the drug intraperitoneally daily during a week before stereotaxic surgery and the last injection was given one hour before stereotaxic surgery. In the second week after surgery, the rotational behavior induced by apomorphine injection within one hour and the number of dopaminergic neurons in the substantia nigra compacta was examined and counted. For statistical analysis, one-way ANOVA and Tukey post-host tests were used in Sigmaplot 12. Results: Chlorogenic acid-pretreated lesion group showed significantly lower rotations versus lesion group (p<0.01). In addition, chlorogenic acid-treated lesion group had a higher number of dopaminergic neurons relative to lesion group (p<0.05). Conclusion: Pretreatment with chlorogenic acid reduces motor asymmetry in an experimental model of Parkinson's disease and has also protective effect on nigral dopaminergic neurons.

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Neuroprotective effect of Pioglitazone in the 6-hydroxydopamine model of Parkinson’s Disease

10.26226/morressier.5785edcfd462b80296c99fd3 ◽

2016 ◽

Author(s):

Maria Vital

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuroprotective Effect ◽

6 Hydroxydopamine

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Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine

Scientific Reports ◽

10.1038/s41598-021-90094-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jui-Chih Chang ◽

Yi-Chun Chao ◽

Huei-Shin Chang ◽

Yu-Ling Wu ◽

Hui-Ju Chang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Olfactory Bulb ◽

Disease Model ◽

Intranasal Delivery ◽

The Difference ◽

And Migration ◽

6 Hydroxydopamine ◽

Locomotor Behaviors ◽

Migratory Stream

AbstractThe feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.

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A Guide to the Generation of a 6-Hydroxydopamine Mouse Model of Parkinson’s Disease for the Study of Non-Motor Symptoms

Biomedicines ◽

10.3390/biomedicines9060598 ◽

2021 ◽

Vol 9 (6) ◽

pp. 598

Author(s):

Débora Masini ◽

Carina Plewnia ◽

Maëlle Bertho ◽

Nicolas Scalbert ◽

Vittorio Caggiano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Survival Rates ◽

Dorsal Striatum ◽

Brain Regions ◽

Motor Symptoms ◽

Operative Care ◽

6 Hydroxydopamine ◽

Non Motor Symptoms

In Parkinson’s disease (PD), a large number of symptoms affecting the peripheral and central nervous system precede, develop in parallel to, the cardinal motor symptoms of the disease. The study of these conditions, which are often refractory to and may even be exacerbated by standard dopamine replacement therapies, relies on the availability of appropriate animal models. Previous work in rodents showed that injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in discrete brain regions reproduces several non-motor comorbidities commonly associated with PD, including cognitive deficits, depression, anxiety, as well as disruption of olfactory discrimination and circadian rhythm. However, the use of 6-OHDA is frequently associated with significant post-surgical mortality. Here, we describe the generation of a mouse model of PD based on bilateral injection of 6-OHDA in the dorsal striatum. We show that the survival rates of males and females subjected to this lesion differ significantly, with a much higher mortality among males, and provide a protocol of enhanced pre- and post-operative care, which nearly eliminates animal loss. We also briefly discuss the utility of this model for the study of non-motor comorbidities of PD.

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