scholarly journals Effects of carnosine and lipoic acid in the late stage of Parkinson’s disease in rats

2019 ◽  
pp. 45-50
Author(s):  
D.S. Berezhnoy ◽  
T.N. Fedorova ◽  
O.I. Kulikova ◽  
A.V. Stavrovskaya ◽  
D.A. Abaimov ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lipoic Acid ◽  
Late Stage ◽  
Right Hemisphere ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Fold Increase ◽  
6 Hydroxydopamine ◽  
The Right

The late stage of Parkinson’s disease is characterized by massive neuronal loss in the substantia nigra (SN) and degeneration of the dopaminergic innervation in the striatum. There is a need to assess the neuroprotective effect of antioxidants (AO) at this stage of the disease. The aim of our study was to assess the efficacy of two AO, carnosine and lipoic acid (LA), in the rat model of late-stage parkinsonism. The pathology was induced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the SN of the right brain hemisphere. AO were administered 4 times, starting on day 14 following the injection of the toxin. We investigated the effect of the injected drugs on the behavior of rats, the loss of neurons in the SN and the metabolism of biogenic neurotransmitter amines. Both AO dampened the development of 6-OHDA-induced neurological and behavioral symptoms. 6-OHDA induced a 90% drop (p = 0.01) in the levels of dopamine (DA) and its metabolites in the right striatum and caused death of over 95% of neurons (p = 0.01) in the SN of the right hemisphere (p = 0.01). AO did not have a significant effect on the number of neurons in the SN but caused an increase in the levels of DA metabolites, as compared to their levels in the animals exposed to 6-OHDA. Elevated DA (a 5.8-fold increase, p = 0.007) was observed only in the animals treated with carnosine. LA stimulated a 23% decline in serotonin levels (p = 0.06) and a 36% increase (p = 0.009) in its metabolite, 5-hydroxyindolacetic acid (5-HIAA). We conclude that although carnosine and LA did not have a direct neuroprotective effect, they could relieve the symptoms. This suggests that these AO could be used as an adjunctive component to antiparkinsonian therapy.

scholarly journals Moxibustion Exerts a Neuroprotective Effect through Antiferroptosis in Parkinson’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Juan Lu ◽  
Xuelei Liu ◽  
Ye Tian ◽  
Hang Li ◽  
Zhenxing Ren ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroprotective Effect ◽  
Disease Model ◽  
Protective Mechanism ◽  
Neural Cells ◽  
Ferritin Heavy Chain ◽  
Functional Pathway ◽  
6 Hydroxydopamine ◽  
The Right

The objective of this study was to explore the neuroprotective effect of moxibustion on rats with Parkinson’s disease (PD) and its mechanism. A Parkinson’s disease model was established in rats using a two-point stereotactic 6-hydroxydopamine injection in the right substantia nigra (SN) and ventral tegmental area. The rats received moxibustion at the Baihui (GV20) and Sishencong (EX-HN1) acupoints for 20 minutes, six times a week, for 6 weeks. The right SN tissue was histologically and immunohistochemically examined. Differentially expressed genes (DEGs) were identified through RNA sequencing. In addition, the levels of tyrosine hydroxylase (TH), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) in SN were measured. In comparison to the model group, the moxibustion group showed a significantly greater TH immunoreactivity and a higher behavioural score. In particular, moxibustion led to an increase in the number and morphological stability of SN neural cells. The functional pathway analysis showed that DEGs are closely related to the ferroptosis pathway. GPX4 and FTH1 in the SN were significantly overexpressed in the moxibustion-treated rats with PD. Moxibustion can effectively reduce the death of SN neurons, decrease the occurrence of ferroptosis, and increase the TH activity to protect the neurons in rats with PD. The protective mechanism may be associated with suppression of the ferroptosis.

Neuroprotective effect of bone marrow derived mesenchymal stem cell secretome in 6-OHDA-induced Parkinson's disease

2021 ◽  
Author(s):  
Dhruv Mahendru ◽  
Ashish Jain ◽  
Seema Bansal ◽  
Deepti Malik ◽  
Neha Dhir ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Bone Marrow ◽  
Parkinson's Disease ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Neuroprotective Effect ◽  
Behavioral Parameters ◽  
Old Rats ◽  
6 Hydroxydopamine

Aim: The aim of the study was to evaluate the neuroprotective effect of bone marrow stem cell secretome in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Materials & methods: Secretome prepared from mesenchymal stem cells of 3-month-old rats was injected daily for 7 days between days 7 and 14 after 6-OHDA administration. After 14 days, various neurobehavioral parameters were conducted. These behavioral parameters were further correlated with biochemical and molecular findings. Results & conclusion: Impaired neurobehavioral parameters and increased inflammatory, oxidative stress and apoptotic markers in the 6-OHDA group were significantly modulated by secretome-treated rats. In conclusion, mesenchymal stem cells-derived secretome could be further explored for the management of Parkinson's disease.

scholarly journals Neuroprotective Mechanisms of Three Natural Antioxidants on a Rat Model of Parkinson’s Disease: A Comparative Study

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 49 ◽  
Author(s):  
Lyubka P. Tancheva ◽  
Maria I. Lazarova ◽  
Albena V. Alexandrova ◽  
Stela T. Dragomanova ◽  
Ferdinando Nicoletti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroprotective Effect ◽  
Memory Performance ◽  
Natural Antioxidants ◽  
Control Group ◽  
Biochemical Assays ◽  
Male Wistar Rats ◽  
Improved Learning ◽  
6 Hydroxydopamine

We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA), α-lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson’s disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals were divided into five groups: the sham-operated (SO) control group; striatal 6-OHDA-lesioned control group; and three groups of 6-OHDA-lesioned rats pre-treated for five days with EA, LA, and Myrt (50 mg/kg; intraperitoneally- i.p.), respectively. On the 2nd and the 3rd week post lesion, the animals were subjected to several behavioral tests: apomorphine-induced rotation; rotarod; and the passive avoidance test. Biochemical evaluation included assessment of main oxidative stress parameters as well as dopamine (DA) levels in brain homogenates. The results showed that all three test compounds improved learning and memory performance as well as neuromuscular coordination. Biochemical assays showed that all three compounds substantially decreased lipid peroxidation (LPO) levels, and restored catalase (CAT) activity and DA levels that were impaired by the challenge with 6-OHDA. Based on these results, we can conclude that the studied AOs demonstrate properties that are consistent with significant antiparkinsonian effects. The most powerful neuroprotective effect was observed with Myrt, and this work represents the first demonstration of its anti-Parkinsonian impact.

Neuroprotective effect of the carnosine – α-lipoic acid nanomicellar complex in a model of early-stage Parkinson's disease

2018 ◽  
Vol 95 ◽  
pp. 254-259 ◽  
Author(s):  
Olga I. Kulikova ◽  
Daniil S. Berezhnoy ◽  
Sergey L. Stvolinsky ◽  
Alexander V. Lopachev ◽  
Valentina S. Orlova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lipoic Acid ◽  
Early Stage ◽  
Neuroprotective Effect

scholarly journals Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration

2020 ◽  
Vol 21 (17) ◽  
pp. 5981
Author(s):  
Ola Wasel ◽  
Jennifer L. Freeman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Dopaminergic System ◽  
Neuronal Loss ◽  
Dopaminergic Neurodegeneration ◽  
Biological Studies ◽  
Vertebrate Model ◽  
Dopaminergic Neuronal Loss ◽  
6 Hydroxydopamine

The zebrafish (Danio rerio) is routinely used in biological studies as a vertebrate model system that provides unique strengths allowing applications in studies of neurodevelopmental and neurodegenerative diseases. One specific advantage is that the neurotransmitter systems are highly conserved throughout vertebrate evolution, including between zebrafish and humans. Disruption of the dopaminergic signaling pathway is linked to multiple neurological disorders. One of the most common is Parkinson’s disease, a neurodegenerative disease associated with the loss of dopaminergic neurons, among other neuropathological characteristics. In this review, the development of the zebrafish’s dopaminergic system, focusing on genetic control of the dopaminergic system, is detailed. Second, neurotoxicant models used to study dopaminergic neuronal loss, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the pesticides paraquat and rotenone, and 6-hydroxydopamine (6-OHDA), are described. Next, zebrafish genetic knockdown models of dj1, pink1, and prkn established for investigating mechanisms of Parkinson’s disease are discussed. Chemical modulators of the dopaminergic system are also highlighted to showcase the applicability of the zebrafish to identify mechanisms and treatments for neurodegenerative diseases such as Parkinson’s disease associated with the dopaminergic system.

scholarly journals A Sequential Intrastriatal Dopaminergic Graft Strategy in the Rodent Model for Parkinson's Disease: Implications for Graft Survival and Targeting

2002 ◽  
Vol 11 (3) ◽  
pp. 185-193 ◽  
Author(s):  
K. A. Baker ◽  
M. B. Purdy ◽  
D. Sadi ◽  
K. Mukhida ◽  
I. Mendez
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Optimal Placement ◽  
Nigrostriatal Pathway ◽  
Total N ◽  
Dopaminergic Grafts ◽  
6 Hydroxydopamine ◽  
The Right ◽  
Final Group ◽  
Important Clinical Implication

Optimal placement of intrastriatal dopaminergic grafts is likely crucial to optimize clinical recovery in Parkinson's disease (PD). The target sites of dopaminergic grafts vary among clinical trials and may partially explain the variable results in clinical efficacy reported thus far. In this study we hypothesized that a subsequent dopaminergic graft may promote functional recovery following a suboptimal initial graft. To test this hypothesis, rats with unilateral 6-hydroxydopamine lesions of the right nigrostriatal pathway were randomly divided into three groups. The first group received 900,000 fetal nigral cells in the medial striatum only (n = 6). The second group received 900,000 cells in both the medial and lateral striatum simultaneously (1.8 million total; n = 8). The final group received a second graft of 900,000 cells in the lateral striatum 6 weeks following initial transplantation of a medial graft (n = 6). Amphetamine-induced circling behavior was significantly reduced in both simultaneous and sequential graft groups at 9 and 12 weeks following transplantation of the initial graft. However, no recovery was noted in the single medial graft group at those time points. Furthermore, increased survival of dopaminergic cells was observed in the lateral graft of sequentially grafted animals compared with the medial graft. We conclude that a well-positioned subsequent graft can restore function in animals with a suboptimal initial graft and that the initial graft may improve survival of the second graft. These results are further discussed in relation to their important clinical implication for neural transplantation in PD.

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