Striatal GDNF affects the motor symptoms of PD by regulating Glu excitotoxicity

Acta Universitatis Medicinalis Anhui 2022 12 v.57 1858-1864     font:big middle small

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Authors:Chen Jing; Xu Nana; Gao Dianshuai

Keywords:Parkinson′s disease;glial cell line-derived neurotrophic factor;glutamic acid;striatum;motor symptom

DOI:10.19405/j.cnki.issn1000-1492.2022.12.002

〔Abstract〕 Objective To explore the mechanism of motor symptoms in Parkinson′s disease(PD) aggravated by decreased glial cell line-derived neurotrophic factor(GDNF) in striatum. Methods Male C57/BL mouse(6-8 weeks), were administered of PBS, AAV-GDNF or AAV-shGDNF in striatum by brain stereoscopic injection, combinated with sub-acute PD model, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) 30 mg/(kg·d)was administered through intraperitoneal injection for five consecutive days; subsequently, mice were randomly divided into PBS group, negative control(NC) group, AAV-shGDNF group, MPTP group, MPTP+AAV-GDNF group, MPTP+AAV-shGDNF group. Behavior tests(rotarod, pole and field) were applied for assessing the motor ability of mice; ELISA kit was used to detect striatal glutamic acid(Glu) content; Western blot and other techniques were carried out to detect the expression and distribution of GLAST, GLT-1 and GluN2 B in striatum; TUNEL staining was applied for observing the apoptosis of neurons in striatum. Results Compared with the NC group,the mice of the AAV-sh GDNF group,with down-regulation of GDNF in striatum,had poor motor ability,decreased Glu transporter( GLAST and GLT-1),and increased Glu content. Compared with the PBS group,the mice of the MPTP group had increased Glu content and decreased Glu N2B in striatum. Compared with the MPTP group,the mice of the MPTP + AAV-GDNF group showed enhanced motor ability,along with decreased Glu content,increased Glu N2B and less neurons apoptosis in striatum; while,the mice of the MPTP + AAV-GDNF group showed worse motor ability,along with augmented Glu content,reduced Glu N2B and more neurons apoptosis in striatum. Conclusion In PD pathological process,decreased striatal GDNF may promote the neurons apoptosis by enhancing Glu excitotoxicity,thereby leading to the aggravation of motor symptoms.