| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 95 === Spinal muscular atrophy (SMA) is characterized by degeneration of the anterior horn cells of the spinal cord, which affects 1/10,000 live births. There are three main types of SMA types I, II and III, based on the severity of the disease and age of onset, and all three types is associated with deletions or mutations in the survival motor neuron 1 (SMN1) gene, which has been designated SMN1 to distinguish from its centromeric homologue, SMN2.
Glial cell line-derived neurotrophic factor (GDNF) has showed its promising effects in protecting and repairing dopamine-containing neurons, which degenerate in Parkinson''s disease, and motoneurons, which die in amyotrophic lateral sclerosis. To investigate the role of GDNF in spinal muscular atrophy (SMA), we analyze GDNF mRNA expression by real-time reverse transcription polymerase chain reaction (RT-PCR) in different tissues from 3-day-old, one-month-old and one-year-old wild type and SMA type 3 mice. Co-cultures of microglial cell (BV-2) and motoneuron cell (NSC-34)/SMN knockdown motoneuron cell (SMN-KD NSC-34; 50% knockdown) were used to detect the GDNF expression under SMN-deficient condition. We also treated the SMN-KD NSC-34 cell by different concentrations of GDNF and proliferation assay and neurite length measurement were applied for evaluating neuroprotective effect.
Our study shows GDNF expression is higher in SMA mice than wild-type mice at newborn and one-month age, but seems opposite in adult age. Higher GDNF mRNA expression when BV-2 cell co-cultured with SMN-KD NSC-34 cell, may indicate SMN deficiency would stimulate GDNF expression. The proliferation assay and neurite length measurement show modest results but further animal model assessment is still suggested. This is a new insight to study the role of GDNF in SMA and may provide new therapeutic strategy of SMA.
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