Cytotoxic T-Cells Cause Hippocampal Sclerosis in an Animal Model of Autoimmune Limbic Encephalitis

سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 474

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شناسه ملی سند علمی:

NIMED03_004

تاریخ نمایه سازی: 7 آبان 1398

چکیده مقاله:

Autoimmune limbic encephalitis (ALE) describes group of autoimmune inflammatory syndromes, often associated with cancer and characterized by neurocognitive impairment, psychiatric symptoms like depression and mesial temporal lobe epilepsy. Magneticresonance imaging (MRI) initially shows an edema with swelling and T2-signal increase of the amygdala and hippocampus which subsequently may turn into hippocampal sclerosis with atrophy and persisting T2- signal increase. In some patients autoantibodies against intracellular neural antigens can be detected in serum and cerebrospinal fluid. In these cases, cytotoxic T cells (CTL) are thought to cause lysis of neuronswhich liberate intracellular antigens that trigger a B cell response with formation of autoantibodies. To better understand the pathophysiological mechanisms, the goal of this study was to develop a CTL-mediated animal model of ALE. To that aim, we took advantageof the Combined Adjuvant for Synergistic Activation of Cellular immunity (CASAC) to induce a CTL-mediated answer against ovalbumin expressing hippocampal CA1 neurons, created via stereotaxic injection of an adenovirus vector encoding for ovalbumin ora control protein under the control of a synapsin promoter. Immunohistochemical staining showed infiltrations of CTLs in the hippocampus leading to astrocytosis, microglia activation and neuronal death.This corresponds to an antigen-dependent hippocampal atrophy as demonstrated by MRI and memory disturbance as revealed by the Novel Object Recognition Test in mice. Taken together, we demonstrate that CTL can cause hippocampal sclerosis in an animal model of ALE.

نویسندگان

Marco Gallus

Institute of Translational Neurology, Department of Neurology, University of Münster, Münster, Germany

Andre Dik

Institute of Translational Neurology, Department of Neurology, University of Münster, Münster, Germany

Veno Narayanan

Institute of Translational Neurology, Department of Neurology, University of Münster, Münster, Germany

Gordon Hicking

Institute of Translational Neurology, Department of Neurology, University of Münster, Münster, Germany