Objective: The aim was to explore the function and mechanism of astrocytic GLT-1 in PD-like changes.
Background: Numerous researches suggest decreased expression of glutamate transporter-1 (GLT-1) is mainly responsible for glutamate excitotoxicity and contribute to the development of Parkinson’s disease (PD). GLT-1 is mainly expressed in astrocytes, and the striatum is a GLT-1-rich brain area. Previous investigations have demonstrated GLT-1 is decreased in the striatum in PD animal models.
Method: In the present study, PD-like changes and their molecular mechanism have been tested by behavioral assessment, micro-PET/CT, western blot, immunohistochemical and immunofluorescence staining, calcium imaging, and ultra performance liquid chromatography with triple quadrupole mass spectrometer after down-regulating astrocytic GLT-1 in the striatum in vivo by brain stereotactic injection of adeno-associated virus (AAV) that carried GLT-1-specific shRNA and in vitro by RNA interference.
Results: In vivo, after 6 weeks of AAV injection, we found that the rats in the astrocytic GLT-1 knockdown group showed poorer motor performance, abnormal gait, and depression-like feature; but no olfactory disorder. The results of micro-PET/CT and western blotting indicated that the dopaminergic system was impaired in astrocytic GLT-1 knockdown rats. Likewise, tyrosine hydroxylase (TH) immune-staining positive neurons of astrocytic GLT-1 knockdown rats showed deficit in cell counting. In vitro, we found that siRNA knockdown of astrocytic GLT-1 led morphological injury of TH-positive neurons, which might have something to do with abnormal calcium signal induced by glutamate accumulation after GLT-1 knockdown. Furthermore, the GLT-1 agonist ceftriaxone showed a protective effect on TH-positive neurons impairment.
Conclusion: The present findings provide a novel Parkinsonian model for further elucidation of the etiological hypotheses of the excitatory amino acid toxicity and shed new light on prevention and treatment of PD based on blocking glutamate excitotoxicity.
To cite this abstract in AMA style:
C. Ren, K-J. He, J-B. Zhang, L-G. Dong, F. Wang, C-F. Liu. Induction of Parkinsonian-like changes via targeted down-regulation of astrocytic glutamate transporter GLT-1 in the striatum [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/induction-of-parkinsonian-like-changes-via-targeted-down-regulation-of-astrocytic-glutamate-transporter-glt-1-in-the-striatum/. Accessed May 24, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/induction-of-parkinsonian-like-changes-via-targeted-down-regulation-of-astrocytic-glutamate-transporter-glt-1-in-the-striatum/