[Different distribution of NMDA receptor subunits in cortex contributes to selective vulnerability of motor neurons in amyotrophic lateral sclerosis].

OBJECTIVE: To investigate the relationship between different distribution of NMDA receptor subunits and motor neurons selective vulnerability in amyotrophic lateral sclerosis. METHODS: First we investigated whether administration of THA, a glutamate transport inhibitor, in cultured organotypic brain tissue made different damage of motor cortex and piriform cortex. Then we testified that selective motor cortex injury was related to disparate distribution of NR2A and NR2B by measuring their protein expression with the method of Western blot. In order to make clear different role of NR2A and NR2B in chronic glutamate excitotoxicity of motor neurons injury, we inhibited NR2A and NR2B separately in cultured cortical motor neurons and brain slices to investigate the mortality changes of motor neurons. RESULTS: The mortality rate of neurons in motor cortex was apparently higher than that of piriform cortex (64.50% ± 2.19% and 30.43% ± 4.75%, P<0.01) after cultured brain slices were damaged by THA 100 µmol/L for two weeks. Western blot results showed that protein expression of NR2B/NR2A ratio in motor cortex was prominently higher than that of piriform cortex (0.87 ± 0.09 and 0.47 ± 0.09, P<0.01). In inhibitor protective experiments, NR2B inhibitor showed positive effects. The mortality rates of cultured cortical motor neurons in control, glutamate, glutamate + NR2A inhibitor, glutamate + NR2B inhibitor were 6.85% ± 1.47%,47.48% ± 5.75%, 45.76% ± 8.09%, 18.10% ± 3.11%, respectively. The mortality rates of cultured motor cortex slices in control, THA, THA + NR2A inhibitor, THA + NR2B inhibitor were 12.49% ± 2.09%,100%,110.87% ± 15.76%, 35.13% ± 5.32%, respectively. CONCLUSION: NR2A and NR2B subunits play different roles in motor neurons chronic glutamate excitotoxicity. Intensive distribution of NR2B subunit in motor cortex makes motor neurons selectively vulnerable to glutamate excitotoxicity in amyotrophic lateral sclerosis.

[Significance of Nogo-A expression of atrophic muscle fibers in diagnosis of amyotrophic lateral sclerosis].

OBJECTIVE: To investigate significance of Nogo-A in atrophic muscle fibers in diagnosis of amyotrophic lateral sclerosis (ALS). METHODS: Forty cases which were diagnosed definitely by clinical, pathological or DNA analysis were included. All of the cases underwent muscle biopsies in order to carry out Nogo-A immunostaining. RESULTS: Nogo-A expression was detected in the atrophic muscle fibers but in either neurogenic disease or myogenic disease, the atrophic muscle fibers demonstrated expression of Nogo-A. As compared with the stainings of NADH-TR and ATPase, it was showed that Nogo-A positive fibers were mainly type I fibers. CONCLUSION: Our results show that the presence of Nogo-A in diseased human muscle biopsies is not limited to ALS, therefore it cannot be the standard for ALS diagnosis.

[Progression rate of MUNE at diagnosis: a prognostic factor of survival in patients with amyotrophic lateral sclerosis].

OBJECTIVE: To identify the correlation between the progression rate of motor unit number estimate (MUNE) at diagnosis and survival. METHODS: We included 129 patents with amyotrophic lateral sclerosis (ALS) enrolled in our hospital from January 2002 to December 2005. We recorded clinical features, ALS functional rating scale (ALSFRS), forced vital capacity (FVC) and electrophysiological data at diagnosis. The patients were monitored every 3 months from visit to death or tracheotomy. RESULTS: Mean age at onset was (52.19+/-11.00) years. The median survival time from symptom onset was 45.71 months (95% CI=35 to 51). In univariate analysis of Kaplan-Meier method, outcome was significantly related to progression rate of MUNE (P<0.05). In the Cox multivariate model, progression rate of MUNE was a significant prognostic factor of survival (P<0.01). Using 2.9/month as cutoff point, the value beyond this point at diagnosis tended to have a shorter survival (P<0.05). A 1-unit decrease in the progression rate of MUNE was associated with a 34.2% decrease risk of death. CONCLUSION: Progression rate of MUNE at diagnosis can provide the information of disease progression at one particular point, which may help to stratify patients and affect survival. It is the strongest prognostic factor of survival in patients with ALS compared with age, onset site and time from onset to diagnosis.