Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
| Autor: | Kyle Williams, Rong-Jian Liu, Christopher Pittenger, Susan E. Swedo, Shaylyn Fahey, Ronald S. Duman, Flora M. Vaccarino, Luciana Romina Frick, James F. Leckman, Jian Xu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Obsessive-Compulsive Disorder Interneuron Mice Transgenic Biology Autoimmune Diseases Mice 03 medical and health sciences 0302 clinical medicine PANDAS Streptococcal Infections Basal ganglia medicine Animals Humans Child Autoantibodies medicine.disease Cholinergic Neurons Corpus Striatum 030227 psychiatry Mice Inbred C57BL Psychiatry and Mental health medicine.anatomical_structure Case-Control Studies Child Preschool Immunoglobulin G biology.protein Cholinergic Female Antibody Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Psychiatry. 178:48-64 |
| ISSN: | 1535-7228 0002-953X |
| Popis: | Pediatric obsessive-compulsive disorder (OCD) sometimes appears rapidly, even overnight, often after an infection. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, describes such a situation after infection withBinding 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 control subjects. 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 several other neuron types, more than IgG from control subjects, in three independent cohorts of patients. Post-IVIG serum had reduced IgG binding to CINs, and 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. |
| Databáze: | OpenAIRE |
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