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BCN 2021, 12(6): 767-776 |
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Voronkov D, Stavrovskaya A, Olshanskiy A, Guschina A, Khudoerkov R, Illarioshkin S. The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted Rats. BCN 2021; 12 (6) :767-776
URL: http://bcn.iums.ac.ir/article-1-1551-en.html
URL: http://bcn.iums.ac.ir/article-1-1551-en.html
Dmitry Voronkov * 
1, Alla Stavrovskaya1 , Artyom Olshanskiy1 , Anastasia Guschina1 , Rudolf Khudoerkov1 , Sergey Illarioshkin1
1, Alla Stavrovskaya1 , Artyom Olshanskiy1 , Anastasia Guschina1 , Rudolf Khudoerkov1 , Sergey Illarioshkin1
1- Research Center of Neurology, Moscow, Russia.
Abstract:
Introduction: Astrocyte dysfunction is the common pathology failing astrocyte-neuron interaction in neurological diseases, including Parkinson’s Disease (PD). The present study aimed to evaluate the impacts of astrocytic dysfunction caused by striatal injections of selective glial toxin L-Aminoadipic Acid (L-AA) on the rats’ locomotor activity in normal conditions and under alpha-methyl-p-tyrosine depletion of catecholamines synthesis.
Methods: Thirty-three male Wistar rats were used in the experiments. Intrastriatal L-AA injections (100 µg) were performed into the right striatum. Alpha-methyl-p-tyrosine (a-MT, 100 mg/kg, inhibitor of tyrosine hydroxylase) was intraperitoneally injected for catecholamine depletion. The animals were divided into 5 groups, as follows: 1. L-AA treated (n=7), 2. L-AA+a-MT treated (n=5), 3. Sham-operated (n=7), 4. Sham+a-MT treated (n=5), 5. Intact control (n=9). For assessing motor function, open field and beam walking tests were used on the third day after the operation. Neuronal and astrocyte markers (glial fibrillary acidic protein, glutamine synthetase, tyrosine hydroxylase, & neuronal nuclear antigen) were examined in the striatum by immunohistochemistry.
Results: Administrating L-AA led to astrocytic degeneration in the striatum. No neuronal death and disruption of dopaminergic terminals were detected. L-AA and a-MT-treated animals’ distance traveled was significantly (P=0.047) shorter than the Sham-operated group injected with a-MT. In the walking beam test, the number of unilateral paw slippings was significantly (P<0.01) higher in the L-AA-treated group than Sham-operated animals. Administrating a-MT alone and L-AA did not change rats’ performance in walking beam tests.
Conclusion: Astrocyte ablation in dopamine depleted striatum resulted in reduced motor activity and asymmetrical gait disturbances. These findings demonstrated the role of astroglia in motor function regulation in the nigrostriatal system and suggest the possible association of glial dysfunction with motor dysfunction in PD.
Methods: Thirty-three male Wistar rats were used in the experiments. Intrastriatal L-AA injections (100 µg) were performed into the right striatum. Alpha-methyl-p-tyrosine (a-MT, 100 mg/kg, inhibitor of tyrosine hydroxylase) was intraperitoneally injected for catecholamine depletion. The animals were divided into 5 groups, as follows: 1. L-AA treated (n=7), 2. L-AA+a-MT treated (n=5), 3. Sham-operated (n=7), 4. Sham+a-MT treated (n=5), 5. Intact control (n=9). For assessing motor function, open field and beam walking tests were used on the third day after the operation. Neuronal and astrocyte markers (glial fibrillary acidic protein, glutamine synthetase, tyrosine hydroxylase, & neuronal nuclear antigen) were examined in the striatum by immunohistochemistry.
Results: Administrating L-AA led to astrocytic degeneration in the striatum. No neuronal death and disruption of dopaminergic terminals were detected. L-AA and a-MT-treated animals’ distance traveled was significantly (P=0.047) shorter than the Sham-operated group injected with a-MT. In the walking beam test, the number of unilateral paw slippings was significantly (P<0.01) higher in the L-AA-treated group than Sham-operated animals. Administrating a-MT alone and L-AA did not change rats’ performance in walking beam tests.
Conclusion: Astrocyte ablation in dopamine depleted striatum resulted in reduced motor activity and asymmetrical gait disturbances. These findings demonstrated the role of astroglia in motor function regulation in the nigrostriatal system and suggest the possible association of glial dysfunction with motor dysfunction in PD.
Type of Study: Original |
Subject:
Behavioral Neuroscience
Received: 2019/07/8 | Accepted: 2020/06/24 | Published: 2021/11/1
Received: 2019/07/8 | Accepted: 2020/06/24 | Published: 2021/11/1
References
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