the influence of striatal astrocyte dysfunction on locomotor activity in dopamine-depleted rats

Introduction: astrocyte dysfunction is the common pathology failing astrocyte-neuroninteraction in neurological diseases, including parkinson’s disease (pd). the present studyaimed to evaluate the impacts of astrocytic dysfunction caused by striatal injections of selectiveglial toxin l-aminoadipic acid (l-aa) on the rats’ locomotor activity in normal conditionsand under alpha-methyl-p-tyrosine depletion of catecholamines synthesis.methods: thirty-three male wistar rats were used in the experiments. intrastriatal l-aainjections (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 catecholaminedepletion. 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. intactcontrol (n=9). for assessing motor function, open field and beam walking tests were used onthe third day after the operation. neuronal and astrocyte markers (glial fibrillary acidic protein,glutamine synthetase, tyrosine hydroxylase, & neuronal nuclear antigen) were examined in thestriatum by immunohistochemistry.results: administrating l-aa led to astrocytic degeneration in the striatum. no neuronal deathand 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 injectedwith 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-mtalone and l-aa did not change rats’ performance in walking beam tests.conclusion: astrocyte ablation in dopamine depleted striatum resulted in reduced motoractivity and asymmetrical gait disturbances. these findings demonstrated the role of astrogliain motor function regulation in the nigrostriatal system and suggest the possible association ofglial dysfunction with motor dysfunction in pd.