Striatal GDNF affects the motor symptoms of PD by regulating Glu excitotoxicity
10.19405/j.cnki.issn1000-1492.2022.12.002
- Author:
Jing Chen
1
;
Nana Xu
1
;
Dianshuai Gao
2
Author Information
1. Experiment Teaching Center of Morphology，Xuzhou Medical University，Xuzhou 221004
2. Teaching and Research Section of Neurobiology，Xuzhou Medical University，Xuzhou 221004
- Publication Type:Journal Article
- Keywords:
Parkinson's disease;
glial cell line-derived neurotrophic factor;
glutamic acid;
striatum;
motor symp- tom
- From:
Acta Universitatis Medicinalis Anhui
2022;57(12):1858-1864
- CountryChina
- Language:Chinese
-
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，com- binated 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 GluN2B in striatum ; TUNEL stainingwas applied for observing the apoptosis of neurons in striatum.
Results :Compared with the NC group，the mice of the AAV-shGDNF group，with down-regulation of GDNF in striatum，had poor motor ability，decreased Glu trans- porter ( 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 GluN2B 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 GluN2B 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 GluN2B 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.
- Full text:2024072115040991646纹状体GDNF调控Glu兴奋性毒性影响PD运动症状_陈静.pdf
