Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies
Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies
复制标题
DOI：
10.1111/j.1460-9568.2010.07349.x
复制
发表时间：
2010-07-01
影响因子：
3.4
通讯作者：
Balice-Gordon, Rita J.
中科院分区：
文献类型：
--
作者：
Moscato, Emilia H.;Jain, Ankit;Balice-Gordon, Rita J.
最近，几个新的，潜在的致命性和治疗反应的综合征，影响海马和皮质功能已被证明与自身抗体对突触抗原，特别是谷氨酸或GABA-B受体。具有这些自身抗体的患者，有时与畸胎瘤和其他肿瘤相关，表现为精神症状、癫痫发作、记忆缺陷和意识水平下降。这些症状通常在免疫治疗或肿瘤切除后显着改善。在这里，我们回顾了这些抗体在体外海马神经元的细胞和突触作用的研究和啮齿动物模型的初步工作。我们的工作表明，患者抗体导致神经递质受体从突触部位快速和可逆地清除，导致突触和回路功能的变化，这反过来又可能导致行为缺陷。我们还讨论了这些和相关疾病提出的许多问题中的几个。确定这些新型抗神经递质受体脑病的潜在机制将为这些疾病的标志性记忆和认知缺陷的细胞和突触基础提供见解，并可能提出治疗干预的途径。
Recently, several novel, potentially lethal and treatment-responsive syndromes that affect hippocampal and cortical function have been shown to be associated with auto-antibodies against synaptic antigens, notably glutamate or GABA-B receptors. Patients with these auto-antibodies, sometimes associated with teratomas and other neoplasms, present with psychiatric symptoms, seizures, memory deficits and decreased levels of consciousness. These symptoms often improve dramatically after immunotherapy or tumor resection. Here we review studies of the cellular and synaptic effects of these antibodies in hippocampal neurons in vitro and preliminary work in rodent models. Our work suggests that patient antibodies lead to rapid and reversible removal of neurotransmitter receptors from synaptic sites, leading to changes in synaptic and circuit function that in turn are likely to lead to behavioral deficits. We also discuss several of the many questions raised by these and related disorders. Determining the mechanisms underlying these novel anti-neurotransmitter receptor encephalopathies will provide insights into the cellular and synaptic bases of the memory and cognitive deficits that are hallmarks of these disorders, and potentially suggest avenues for therapeutic intervention.