Hippocampal epileptogenesis in autoimmune encephalitis
| العنوان: | Hippocampal epileptogenesis in autoimmune encephalitis |
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| المؤلفون: | Paolo Calabresi, Elena Nardi Cesarini, Andrea Mancini, Arjune Sen, Sarosh R. Irani, Diego Franciotta, Lucilla Parnetti, Paraskevi Krashia, Pasquale Nigro, Nicola Biagio Mercuri, Matteo Gastaldi, Massimiliano Di Filippo, Nicola Tambasco, Cinzia Costa, Annalisa Nobili, Marcello D'Amelio, Michele Romoli |
| المصدر: | Annals of Clinical and Translational Neurology Annals of Clinical and Translational Neurology, Vol 6, Iss 11, Pp 2261-2269 (2019) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, neurological disorders, Neurosciences. Biological psychiatry. Neuropsychiatry, Nerve Tissue Proteins, Hippocampal formation, Epileptogenesis, Autoantigens, Hippocampus, 03 medical and health sciences, Mice, 0302 clinical medicine, Autoimmune Diseases of the Nervous System, Medicine, Premovement neuronal activity, Animals, Humans, RC346-429, Research Articles, Autoantibodies, Autoimmune encephalitis, Neurons, Epilepsy, business.industry, General Neuroscience, autoimmune encephalitis, Glutamate receptor, Intracellular Signaling Peptides and Proteins, Membrane Proteins, 3. Good health, Mice, Inbred C57BL, Electrophysiology, Settore MED/26 - NEUROLOGIA, 030104 developmental biology, medicine.anatomical_structure, nervous system, Receptors, GABA-B, Schaffer collateral, Encephalitis, Neurology. Diseases of the nervous system, Neurology (clinical), business, Neuroscience, 030217 neurology & neurosurgery, Ex vivo, RC321-571, Research Article |
| الوصف: | Objective Autoantibody‐mediated forms of encephalitis (AE) include neurological disorders characterized by subacute memory loss, movement disorders, and, often, frequent, focal epileptic seizures. Yet, the electrophysiological effects of these autoantibodies on neuronal function have received little attention. In this study, we assessed the effects of CSF containing autoantibodies on intrinsic and extrinsic properties of hippocampal neurons, to define their epileptogenic potential. Methods We compared the effects of CSF containing leucine‐rich glioma inactivated 1 (LGI1), contactin‐associated protein‐like 2 (CASPR2), and γ‐aminobutyric acid receptor B (GABABR) antibodies on ex vivo electrophysiological parameters after stereotactic hippocampal inoculation into mice. Whole‐cell patch‐clamp and extracellular recordings from CA1 pyramidal neurons and CA3‐CA1 field recordings in ex vivo murine brain slices were used to study neuronal function. Results By comparison to control CSF, AE CSFs increased the probability of glutamate release from CA3 neurons. In addition, LGI1‐ and CASPR2 antibodies containing CSFs induced epileptiform activity at a population level following Schaffer collateral stimulation. CASPR2 antibody containing CSF was also associated with higher spontaneous firing of CA1 pyramidal neurons. On the contrary, GABABR antibody containing CSF did not elicit changes in intrinsic neuronal activity and field potentials. Interpretation Using patient CSF, we have demonstrated that the AE‐associated antibodies against LGI1 and CASPR2 are able to increase hippocampal CA1 neuron excitability, facilitating epileptiform activity. These findings provide in vivo pathogenic insights into neuronal dysfunction in these conditions. |
| تدمد: | 2328-9503 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e330a199b1df21ee1b37bf21473eab0bTest https://pubmed.ncbi.nlm.nih.gov/31617317Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e330a199b1df21ee1b37bf21473eab0b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23289503 |
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