Hericium erinaceus potentially rescues behavioural motor deficits through ERK-CREB-PSD95 neuroprotective mechanisms in rat model of 3-acetylpyridine-induced cerebellar ataxia
Hericium erinaceus potentially rescues behavioural motor deficits through ERK-CREB-PSD95 neuroprotective mechanisms in rat model of 3-acetylpyridine-induced cerebellar ataxia
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DOI：
10.1038/s41598-020-71966-z
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发表时间：
2020-09-10
影响因子：
4.6
通讯作者：
Lim, Lee Wei
中科院分区：
文献类型：
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作者：
Chong, Pit Shan;Khairuddin, Sharafuddin;Lim, Lee Wei
小脑共济失调是一种神经退行性疾病，目前尚无明确的治疗方法。虽然一些研究已经证明了猴头菌（H.E.）的神经保护作用，其在小脑性共济失调中的机制仍不清楚。在这里，我们研究了H.E.在3-乙酰吡啶（3-AP）诱导的小脑共济失调的动物模型中的治疗。3-AP注射给药的动物在运动协调和平衡方面表现出显著的损伤。25 mg/kg H.E. 3-AP治疗组与3-AP生理盐水组相比。有趣的是，与非3-AP对照组相比，3-AP治疗组也没有显著差异，表明运动缺陷的潜在补救。结果表明，25 mg/kg H.E.使神经可塑性相关基因表达正常化至非3-AP对照的水平。与3-AP盐水组相比，3-AP治疗组中pERK 1/2-pCREB-PSD 95蛋白表达增加以及对小脑浦肯野细胞的神经保护作用进一步支持了这些发现。总之，我们的研究结果表明HE在3-AP诱导的小脑共济失调动物模型中，通过ERK-CREB-PSD 95的神经保护机制潜在地挽救了行为运动缺陷。
Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although several studies have demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), its mechanisms in cerebellar ataxia remain largely unknown. Here, we investigated the neuroprotective effects of H.E. treatment in an animal model of 3-acetylpyridine (3-AP)-induced cerebellar ataxia. Animals administered 3-AP injection exhibited remarkable impairments in motor coordination and balance. There were no significant effects of 25 mg/kg H.E. on the 3-AP treatment group compared to the 3-AP saline group. Interestingly, there was also no significant difference in the 3-AP treatment group compared to the non-3-AP control, indicating a potential rescue of motor deficits. Our results revealed that 25 mg/kg H.E. normalised the neuroplasticity-related gene expression to the level of non-3-AP control. These findings were further supported by increased protein expressions of pERK1/2-pCREB-PSD95 as well as neuroprotective effects on cerebellar Purkinje cells in the 3-AP treatment group compared to the 3-AP saline group. In conclusion, our findings suggest that H.E. potentially rescued behavioural motor deficits through the neuroprotective mechanisms of ERK-CREB-PSD95 in an animal model of 3-AP-induced cerebellar ataxia.