The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted Rats
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-Aminoadipi...
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| Format: | Article |
| Language: | English |
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Iran University of Medical Sciences
2021-11-01
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| Series: | Basic and Clinical Neuroscience |
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| Online Access: | http://bcn.iums.ac.ir/article-1-1551-en.html |
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| author | Dmitry Voronkov Alla Stavrovskaya Artyom Olshanskiy Anastasia Guschina Rudolf Khudoerkov Sergey Illarioshkin |
| author_facet | Dmitry Voronkov Alla Stavrovskaya Artyom Olshanskiy Anastasia Guschina Rudolf Khudoerkov Sergey Illarioshkin |
| author_sort | Dmitry Voronkov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T18:09:04Z |
| format | Article |
| id | doaj.art-f01268a8aa8641c1adbae729615d45bd |
| institution | Directory Open Access Journal |
| issn | 2008-126X 2228-7442 |
| language | English |
| last_indexed | 2024-03-07T18:09:04Z |
| publishDate | 2021-11-01 |
| publisher | Iran University of Medical Sciences |
| record_format | Article |
| series | Basic and Clinical Neuroscience |
| spelling | doaj.art-f01268a8aa8641c1adbae729615d45bd2024-03-02T08:06:12ZengIran University of Medical SciencesBasic and Clinical Neuroscience2008-126X2228-74422021-11-01126767776The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted RatsDmitry Voronkov0Alla Stavrovskaya1Artyom Olshanskiy2Anastasia Guschina3Rudolf Khudoerkov4Sergey Illarioshkin5 Research Center of Neurology, Moscow, Russia. Research Center of Neurology, Moscow, Russia. Research Center of Neurology, Moscow, Russia. Research Center of Neurology, Moscow, Russia. Research Center of Neurology, Moscow, Russia. Research Center of Neurology, Moscow, Russia. 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.http://bcn.iums.ac.ir/article-1-1551-en.htmlastrocyte2-aminoadipic acidalpha-methyltyrosinecorpus striatummotor activity |
| spellingShingle | Dmitry Voronkov Alla Stavrovskaya Artyom Olshanskiy Anastasia Guschina Rudolf Khudoerkov Sergey Illarioshkin The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted Rats Basic and Clinical Neuroscience astrocyte 2-aminoadipic acid alpha-methyltyrosine corpus striatum motor activity |
| title | The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted Rats |
| title_full | The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted Rats |
| title_fullStr | The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted Rats |
| title_full_unstemmed | The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted Rats |
| title_short | The Influence of Striatal Astrocyte Dysfunction on Locomotor Activity in Dopamine-depleted Rats |
| title_sort | influence of striatal astrocyte dysfunction on locomotor activity in dopamine depleted rats |
| topic | astrocyte 2-aminoadipic acid alpha-methyltyrosine corpus striatum motor activity |
| url | http://bcn.iums.ac.ir/article-1-1551-en.html |
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