Shahani Neelam, Gourie-Devi M, Nalini A, Rammohan Priti, Shobha K, Harsha H N, Raju T R
Department of Neurobiology, University of Osnabrueck, D- 49076 Osnabrueck, Germany.
Amyotroph Lateral Scler Other Motor Neuron Disord. 2004 Sep;5(3):172-9. doi: 10.1080/14660820410017037.
Previous studies from our laboratory suggest the presence of toxic factor(s) in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS) which induces degenerative changes in the spinal cord neurons. The present work was carried out to investigate the role of (-)-deprenyl in attenuating these degenerative changes. CSF samples from ALS and non-ALS neurological patients were injected into the spinal subarachnoid space of 3-day-old rat pups, followed by a single dose (0.01 mg/kg body weight) of (-)-deprenyl, administered 24 h after CSF injection. After a further period of 24 h, the rats were sacrificed and the spinal cord sections were stained with antibodies against phosphorylated neurofilament (NF, SMI-31 antibody) and glial fibrillary acidic protein (GFAP). Activity of lactate dehydrogenase (LDH) was also measured. (-)-Deprenyl injection resulted in a significant (61%) decrease in the number of SMI-31 stained neuronal soma in the ventral horn of the spinal cord of ALS CSF exposed rats. This was accompanied by a reduction in the astrocytes immunoreactive for GFAP. There was also a significant (35%) decrease in the LDH activity following (-)-deprenyl treatment. These results suggest that (-)-deprenyl may confer neuroprotection against the toxic factor(s) present in ALS CSF.
我们实验室之前的研究表明,肌萎缩侧索硬化症(ALS)患者的脑脊液(CSF)中存在毒性因子,可诱导脊髓神经元发生退行性变化。本研究旨在探讨(-)-司来吉兰在减轻这些退行性变化中的作用。将ALS和非ALS神经系统疾病患者的脑脊液样本注入3日龄幼鼠的脊髓蛛网膜下腔,然后在脑脊液注射24小时后给予单剂量(0.01mg/kg体重)的(-)-司来吉兰。再过24小时后,处死大鼠,用抗磷酸化神经丝(NF,SMI-31抗体)和胶质纤维酸性蛋白(GFAP)的抗体对脊髓切片进行染色。还测量了乳酸脱氢酶(LDH)的活性。注射(-)-司来吉兰后,暴露于ALS脑脊液的大鼠脊髓腹角中SMI-31染色的神经元胞体数量显著减少(61%)。这伴随着对GFAP免疫反应阳性的星形胶质细胞减少。(-)-司来吉兰治疗后,LDH活性也显著降低(35%)。这些结果表明,(-)-司来吉兰可能对ALS脑脊液中存在的毒性因子具有神经保护作用。