Neuropathology in respiratory-related motoneurons in young Pompe (Gaa(-/-)) mice.
Neuropathology in respiratory-related motoneurons in young Pompe (Gaa(-/-)) mice.
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DOI：
10.1016/j.resp.2016.02.007
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发表时间：
2016-06-15
影响因子：
2.3
通讯作者：
Fuller DD
中科院分区：
文献类型：
--
作者：
Turner SM;Hoyt AK;ElMallah MK;Falk DJ;Byrne BJ;Fuller DD
呼吸和/或舌功能障碍是庞贝病的首要运动症状之一，庞贝病是一种由于溶酶体酶酸性 α-葡萄糖苷酶 (GAA) 缺失或功能障碍而导致的疾病。在这里，我们对 6 周大的无症状 Pompe (Gaa−/−) 小鼠的髓质、颈椎和胸椎脊髓进行了组织学评估，以确定呼吸运动区的神经病理学是否早发。高碘酸希夫 (PAS) 染色表明糖原积累仅发生在 Gaa−/− 舌下、中颈和上胸运动神经元中。 DNA 损伤 (Tunel) 和正在进行的细胞凋亡 (Cleaved Caspase 3) 标记物并不与 PAS 染色共定位，但在包括孤束核在内的髓质区域以及胸椎背角中很突出。我们得出的结论是，呼吸相关运动神经元特别容易受到 GAA 缺乏的影响，并且神经元糖原积累和神经变性可能在疾病早期独立发生。这些数据支持庞贝病的早期治疗干预。
Respiratory and/or lingual dysfunction are among the first motor symptoms in Pompe disease, a disorder resulting from absence or dysfunction of the lysosomal enzyme acid α-glucosidase (GAA). Here, we histologically evaluated the medulla, cervical and thoracic spinal cords in 6 weeks old asymptomatic Pompe (Gaa−/−) mice to determine if neuropathology in respiratory motor regions has an early onset. Periodic acid-Schiff (PAS) staining indicated glycogen accumulation was exclusively occurring in Gaa−/− hypoglossal, mid-cervical and upper thoracic motoneurons. Markers of DNA damage (Tunel) and ongoing apoptosis (Cleaved Caspase 3) did not co-localize with PAS staining, but were prominent in a medullary region which included the nucleus tractus solitarius, and also in the thoracic spinal dorsal horn. We conclude that respiratory-related motoneurons are particularly susceptible to GAA deficiency and that neuronal glycogen accumulation and neurodegeneration may occur independently in early stage disease. The data support early therapeutic intervention in Pompe disease.