抗IgLON5疾病是一种罕见的迟发性神经系统疾病,与IgLON5自身抗体相关,磷酸化Tau蛋白(p-Tau)的神经元积累,和睡眠,呼吸,和电机改造。
我们进行了一项初步研究,研究抗IgLON5疾病的神经病理学和临床特征是否可以在慢性脑室内输注人抗IgLON5疾病IgG(Pt-IgG)的小鼠中重现。
将表达人Tau蛋白的人源化转基因hTau小鼠和野生型(WT)对照小鼠侧脑室内输注Pt-IgG或来自对照受试者的抗体14天。睡眠,呼吸,在抗体输注结束时和之后至少30天评估运动表型,然后对p-Tau沉积进行免疫组织化学评估。
在输注Pt-IgG的雌性hTau和WT小鼠中,我们发现脑干和海马中弥漫性神经元细胞质p-Tau沉积的可重复趋势,睡眠期间通气期增加,睡觉时舔间隔时间减少。这些发现在雄性hTau小鼠上没有重复。
我们的初步研究结果表明,但不证明,小鼠慢性ICV输注Pt-IgG可能引起神经病理,呼吸,和电机改造。这些结果应该被认为是初步的,直到在考虑到小鼠潜在性别差异的更大研究中重复。
Anti-IgLON5 disease is a rare late-onset neurological disease associated with autoantibodies against IgLON5, neuronal accumulation of phosphorylated Tau protein (p-Tau), and sleep, respiratory, and motor alterations.
We performed a pilot study of whether the neuropathological and clinical features of anti-IgLON5 disease may be recapitulated in mice with chronic intracerebroventricular infusion of human anti-IgLON5 disease IgG (Pt-IgG).
Humanized transgenic hTau mice expressing human Tau protein and wild-type (WT) control mice were infused intracerebroventricularly with Pt-IgG or with antibodies from a control subject for 14 days. The sleep, respiratory, and motor phenotype was evaluated at the end of the antibody infusion and at least 30 days thereafter, followed by immunohistochemical assessment of p-Tau deposition.
In female hTau and WT mice infused with Pt-IgG, we found reproducible trends of diffuse neuronal cytoplasmic p-Tau deposits in the brainstem and hippocampus, increased ventilatory period during sleep, and decreased inter-lick interval during wakefulness. These findings were not replicated on male hTau mice.
The results of our pilot study suggest, but do not prove, that chronic ICV infusion of mice with Pt-IgG may elicit neuropathological, respiratory, and motor alterations. These results should be considered as preliminary until replicated in larger studies taking account of potential sex differences in mice.