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1- Research center of neurology

Introduction: Astrocyte dysfunction is the common pathology resulting in failure of astrocyte-neuron interaction in neurological diseases, including Parkinson’s disease (PD). To date, only few experimental models of selective ablation of astrocytes are known. The aim of present study was to evaluate the effect of striatal injections of selective glial toxin L-aminoadipic acid (L-AA) on the locomotor activity in L-AA-treated catecholamine-depleted animals and in L-AA-treated saline-injected rats.

Materials and Methods. Wistar rats (n=12) were stereotaxically, unilaterally injected with L-AA (100 µg in 5 µl phosphate buffered saline) into the right striatum. Control, sham-operated rats (n=12) received PBS (5 μl). Intact control group (n=9) received no treatments. Two groups of L-AA-treated (n=5) and sham-operated (n=5) rats were intraperitoneally injected with alpha-methyl-p-tyrosine (a-MT, 100 mg/kg) one hour before locomotor activity testing. After intrastriatal injections effect of L-AA administration on locomotor activity was evaluated on the 3-rd day in open field and beam walking tests. Immunohistochemical localization of neuronal and astrocyte markers such as GFAP, glutamine synthetase, tyrosine hydroxylase and NeuN in striatum of randomly selected L-AA-treated (n=5) and sham-operated (n=5) animals was examined.

Results. Intrastriatal L-AA administration led to astrocytic degeneration in the injection site. No neuronal degeneration and disruption of nigrostriatal dopaminergic terminals in striatum were detected in 72 hours after L-AA injection. Astrocyte ablation in striatum resulted in reduced motor activity and asymmetrical gait disturbances. Dopamine depletion facilitated bradykinesia caused by astrocyte ablation.

Conclusion. These findings demonstrate a 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

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