[Effects of glutamate transport inhibitor on organotypic cultured spinal cord slices].
This study was aimed at investigating the effect of glutamate on motor neurons in organotypic cultured spinal cord slices treated by threohydroxyaspartate (THA), an inhibitor of glutamate transporter. The spinal cord cultures were prepared using lumbar spinal cord slices from 8-day-old rat. Various concentration of THA(50 micromol/L,100 micromol/L,500 micromol/L) was added into the culture medium respectively. Ventral alpha-motor neurons survival was evaluated by immunohistochemistry staining monoclonal antibody SMI-32, a nonphosphorylated neurofilament marker, and interneurons in dorsal horn were identified by monoclonal anti-calretinin antibody staining. Lactate dehydrogenase (LDH) level in the culture medium was also measured. The spinal cord slices in the control group could maintain excellent organotypic cellular organization and a stable population of ventral alpha-motor neurons. THA caused a slow dose-dependent loss of alpha-motor neurons and an increase in LDH enzyme activity in the culture medium while dorsal interneurons were less damaged. 100 micromol/L THA resulted in a significant decrease in (alpha-motor neurons after cultured for 4 weeks. On the contrary, the interneurons in the dorsal horn were less affected. It was also observed in patients with amyotrophic lateral sclerosis (ALS). Excellular Glu mainly caused selective alpha-motor neuron death, and motoneurons were more sensitive to glutamate excitotoxicity than sensory neurons in the spinal cord.
Xiao
Xiang Jian
XJ
Department of Neurology, the Second Hospital of Hebei Medical University, Shijiazhuang, 050000.
Wang
Xiao Juan
XJ
Wang
Li Qin
LQ
Song
Xue Qin
XQ
Liu
Wi Gong
WG
Zheng
M A
MA
Li
Chum Yan
CY
D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism*; D006836:Hydro-Lyases / Q000378:metabolism; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects; D009924:Organ Culture Techniques / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects*
D001224:Aspartic Acid; D018698:Glutamic Acid; D006836:Hydro-Lyases; C045581:lactate dehydratase