Mitochondrial inhibition induces glutamate excitotoxicity mediated motoneuron death
- VernacularTitle:运动神经元线粒体抑制后产生谷氨酸毒性损伤
- Author:
Mei ZHENG
;
Dongsheng FAN
;
Jun ZHANG
;
Demao SONG
;
Shaoguang FAN
- Publication Type:Journal Article
- Keywords:
Motor neuron disease;
Malonates;
Mitochondria;
Oizocilpine maleate;
Glutamic acid
- From:
Chinese Journal of Neurology
2005;0(11):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the relation between mitochondria damage and glutamate excitotoxicity in motor neuron disease.Methods Organotypic cerebral cultures were prepared from prefrontal brain of neonatal SD rats. Mitochondria was damaged by malonate sodium, and a NMDA receptor antagonist, MK-801 of 0.025,0.050,0.075,0.100 mmol/L, was respectively added into the cerebral cultures simultaneously in the protective experiment. The morphology of motor neurons was shown by Nissl and anti-high molecular weight filament (anti-NFH) immunohistochemical staining, and number of motor neurons was counted. The concentration of MDA in culture medium was measured by MDA assay. Results After exposed to malonate sodium (0, 1, 3, 5 and 7 mmol/L) for 1 week, the number of motor neurons in cerebral slices showed a dose-dependent decrease (49.78?4.30, 47.89?6.81, 25.67?6.18, 4.44?3.40, 1.22?1.99). The group treated with 3 mmol/L malonate sodium was selected as damage group. In protective experiment, the number of motor neurons in 0.050, 0.075 and 0.100 mmol/L MK-801-treated groups was significantly increased as compared with damage group, still less than that of controls. However, there was no difference of number of motor neurons among these three groups. The concentration of MDA in culture medium in normal control and 3, 5 mmol/L malonate sodium was (13.47?0.49), (15.87?0.74), (20.52?0.74) mmol/L. When treating cerebral cultures with 0.050 mmol/L MK-801 and 5 mmol/L malonate sodium simultaneously, the MDA was decreased to 14.45?0.78, close to normal level. Conclusion Glutamate excitotoxicity plays a role in motor neuron diseases caused by mitochondria damage, there exists a close relationship between glutamate exicitotoxicity and mitochondria damage.
