Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity.
Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity.
复制标题
DOI：
10.1176/appi.ajp.2020.19070698
复制
发表时间：
2021-01-01
期刊：
影响因子：
--
通讯作者：
Pittenger C
中科院分区：
文献类型：
--
作者：
Xu J;Liu RJ;Fahey S;Frick L;Leckman J;Vaccarino F;Duman RS;Williams K;Swedo S;Pittenger C
儿童强迫症(OCD)有时会迅速出现，甚至在一夜之间出现，通常是在感染之后。儿童自身免疫性神经精神障碍与链球菌或熊猫相关，描述了感染化脓性链球菌后的这种情况。熊猫可能是由于诱导了对大脑抗原的自身免疫而产生的，尽管这一点仍未得到证实。试点工作表明，来自大熊猫儿童的免疫球蛋白抗体与纹状体中的胆碱能中间神经元(CINs)结合。CIN缺乏症已经独立地与人类抽搐和小鼠重复的行为病理联系在一起，使其成为一个看似合理的病理位点。将27只患有严格特征的大熊猫的儿童和23名匹配的对照组儿童的血清与血清孵育后，体外评估了人和小鼠脑片中特定神经元与免疫球蛋白的结合情况。结合程度与症状程度相关。用分子标记和电生理记录评估血清孵育后小鼠脑片的神经活动。在三个独立的患者队列中，患有熊猫的儿童的免疫球蛋白与CIN结合，但不与多种其他神经元类型结合，而不是来自对照的免疫球蛋白。IVIG降低了免疫球蛋白与CIN的结合；这种减少与症状的改善有关。在急性脑片中，基线大熊猫血清降低纹状体CINs的活性，但不降低表达小白蛋白的GABA能中间神经元的活性，并改变它们的电生理反应。静脉注射免疫球蛋白后的大熊猫血清和去免疫球蛋白的基线血清不改变纹状体CIN的活性。这些发现为纹状体CINs作为一个关键的细胞靶点提供了强有力的证据，这可能有助于快速发作的强迫症症状的儿童的病理生理学，也许在其他情况下也是如此。
Pediatric obsessive-compulsive disorder (OCD) sometimes appears rapidly, even overnight, often after an infection. Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus, or PANDAS, describes such a situation after infection with Streptococcus pyogenes. PANDAS may result from induced autoimmunity against brain antigens, though this remains unproven. Pilot work suggests that IgG antibodies from children with PANDAS bind to cholinergic interneurons (CINs) in the striatum. CIN deficiency has been independently associated with tics in humans and with repetitive behavioral pathology in mice, making it a plausible locus of pathology. Binding of IgG to specific neurons in human and mouse brain slices was evaluated ex vivo after incubation with serum from 27 children with rigorously characterized PANDAS, both at baseline and after intravenous immunoglobulin (IVIG) treatment, and 23 matched controls. Binding was correlated with symptom measures. Neural activity after serum incubation was assessed in mouse slices using molecular markers and electrophysiological recording. IgG from children with PANDAS bound to CINs, but not to multiple other neuron types, more than IgG from controls, in three independent cohorts of patients. IVIG reduced IgG binding to CINs; this reduction correlated with symptom improvement. Baseline PANDAS sera decreased activity of striatal CINs, but not of parvalbumin-expressing GABAergic interneurons, and altered their electrophysiological responses, in acute mouse brain slices. Post-IVIG PANDAS sera and IgG-depleted baseline sera did not alter the activity of striatal CINs. These findings provide strong evidence for striatal CINs as a critical cellular target that may contribute to pathophysiology in children with rapid-onset OCD symptoms, and perhaps in other conditions.
登录
查看更多内容
DOI：
10.1111/ejn.12915
发表时间：
2015-07
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Faust TW;Assous M;Shah F;Tepper JM;Koós T
通讯作者：
Koós T
影响因子：
3.7
作者：
Higley, Michael J.;Gittis, Aryn H.;Sabatini, Bernardo L.
通讯作者：
Sabatini, Bernardo L.
影响因子：
48
作者：
Dalmau, Josep;Gleichman, Amy J.;Hughes, Ethen G.;Rossi, Jeffrey E.;Peng, Xiaoyu;Lai, Meizan;Dessain, Scott K.;Rosenfeld, Mynna R.;Balice-Gordon, Rita;Lynch, David R.
通讯作者：
Lynch, David R.
影响因子：
3.7
作者：
Bertran-Gonzalez, Jesus;Chieng, Billy C.;Balleine, Bernard W.
通讯作者：
Balleine, Bernard W.
影响因子：
1.9
作者：
Chang, Kiki;Frankovich, Jennifer;Swedo, Susan E.
通讯作者：
Swedo, Susan E.