scholarly journals Development of an Alpha-synuclein Based Rat Model for Parkinson's Disease via Stereotactic Injection of a Recombinant Adeno-associated Viral Vector

Author(s):  
Anke Van der Perren ◽  
Cindy Casteels ◽  
Koen Van Laere ◽  
Rik Gijsbers ◽  
Chris Van den Haute ◽  
...  
2013 ◽  
Vol 56 ◽  
pp. 47-58 ◽  
Author(s):  
Fabia Febbraro ◽  
Gurdal Sahin ◽  
Aina Farran ◽  
Sofia Soares ◽  
Poul H. Jensen ◽  
...  

2015 ◽  
Vol 36 (3) ◽  
pp. 1543-1558 ◽  
Author(s):  
Anke Van der Perren ◽  
Jaan Toelen ◽  
Cindy Casteels ◽  
Francesca Macchi ◽  
Anne-Sophie Van Rompuy ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Martijn Devrome ◽  
Cindy Casteels ◽  
Anke Van der Perren ◽  
Koen Van Laere ◽  
Veerle Baekelandt ◽  
...  

Author(s):  
Teresa Torre-Muruzabal ◽  
Jens Devoght ◽  
Chris Van den Haute ◽  
Bert Brône ◽  
Anke Van der Perren ◽  
...  

Abstract Aggregation of alpha-synuclein (α-SYN) is the pathological hallmark of several diseases named synucleinopathies, including Parkinson’s disease (PD), which is the most common neurodegenerative motor disorder. Alpha-SYN has been linked to synaptic function both in physiological and pathological conditions. However, the exact link between neuronal activity, α-SYN toxicity and disease progression in PD is not clear. In this study, we aimed to investigate the effect of chronic neuromodulation in an α-SYN-based rat model for PD using chemogenetics. To do this, we expressed excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) combined with mutant A53T α-SYN, using two different recombinant adeno-associated viral (rAAV) vectors (serotypes 2/7 and 2/8) in rat substantia nigra (SN) and investigated the effect on motor behavior, synapses and neuropathology. We found that chronic neuromodulation aggravates motor deficits induced by α-SYN, without altering dopaminergic neurodegeneration. In addition, neuronal activation led to changes in post-translational modification and subcellular localization of α-SYN, linking neuronal activity to the pathophysiological role of α-SYN in PD.


Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2182 ◽  
Author(s):  
Richard L. Jayaraj ◽  
Rami Beiram ◽  
Sheikh Azimullah ◽  
Mohamed Fizur Nagoor Meeran ◽  
Shreesh K. Ojha ◽  
...  

Parkinson’s disease, a chronic, age related neurodegenerative disorder, is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Several studies have proven that the activation of glial cells, presence of alpha-synuclein aggregates, and oxidative stress, fuels neurodegeneration, and currently there is no definitive treatment for PD. In this study, a rotenone-induced rat model of PD was used to understand the neuroprotective potential of Lycopodium (Lyc), a commonly-used potent herbal medicine. Immunohistochemcial data showed that rotenone injections significantly increased the loss of dopaminergic neurons in the substantia nigra, and decreased the striatal expression of tyrosine hydroxylase. Further, rotenone administration activated microglia and astroglia, which in turn upregulated the expression of α-synuclein, pro-inflammatory, and oxidative stress factors, resulting in PD pathology. However, rotenone-injected rats that were orally treated with lycopodium (50 mg/kg) were protected against dopaminergic neuronal loss by diminishing the expression of matrix metalloproteinase-3 (MMP-3) and MMP-9, as well as reduced activation of microglia and astrocytes. This neuroprotective mechanism not only involves reduction in pro-inflammatory response and α-synuclein expression, but also synergistically enhanced antioxidant defense system by virtue of the drug’s multimodal action. These findings suggest that Lyc has the potential to be further developed as a therapeutic candidate for PD.


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