Neuroinflammation has been classified as a trigger of behavioral alterations and cognitive impairments in many neurological conditions, including Alzheimer's disease, major depression, anxiety and others. Regardless of the cause of neuroinflammation, key molecules, which sense neuropathological conditions, are intracellular multiprotein signaling inflammasomes. Increasing evidence shows that the inflammatory response, mediated by activated nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasomes, is associated with the onset and progression of a wide range of diseases of the CNS. However, whether the NLRP3 inflammasome in the CNS is involved in the learning, development of anxiety and adult neurogenesis remains elusive. Therefore, the present study was designed to assess NLRP3 inflammasome contribution in anxiety and reveal its potential involvement in the experimental acquisition of fear responses and hippocampal neurogenesis. Behavioral, immunohistochemical and electrophysiological alterations were measured to evaluate role of neuroinflammation in the limbic system of mice.

In this study, we describe interrelated neurophysiological mechanisms, which culminate in absence of NLRP3 inflammasome in young 4 months mice. These include the following: anxious behavior and deterioration in learning and memory of fear conditioning; impairment of adult neurogenesis; reduction and altered morphology of astrocytes in the brain; hyperexcitability in basolateral amygdala (BLA); impaired activation in axons of pyramidal cells of CA1 hippocampal zone in NLRP3 KO mice particularly via the Schaffer collateral pathway; and impaired synaptic transduction in pyramidal cells mediated by an embarrassment of neurotransmitter release from presynaptic site in CA3 hippocampal zone.

The present study has demonstrated the novel findings that basal level of NLRP3 inflammasome in the brain of young mice is required for conditioning-induced plasticity in the ventral hippocampus and the basolateral amygdala. The deletion of NLRP3 impair synaptic transduction and caused anxiety-like behavior and labored fear learning, suggesting that low grade inflammation, mediated by NLRP3 expression, play a key role in memory consolidation.

神经炎症已被归类为许多神经系统疾病的行为改变和认知障碍的触发因素，包括阿尔茨海默病、重度抑郁症、焦虑症等。无论神经炎症的原因如何，感知神经病理学状况的关键分子都是细胞内多蛋白信号炎症小体。越来越多的证据表明，由激活的核苷酸结合寡聚结构域、富含亮氨酸的重复结构域和含有吡啶结构域的 3 (NLRP3) 炎性体介导的炎症反应与多种 CNS 疾病的发生和进展有关. 然而，中枢神经系统中的 NLRP3 炎症小体是否与学习、焦虑的发展和成人神经发生有关仍然难以捉摸。所以，本研究旨在评估 NLRP3 炎症小体在焦虑中的作用，并揭示其在实验获得恐惧反应和海马神经发生中的潜在作用。测量行为、免疫组织化学和电生理学改变以评估神经炎症在小鼠边缘系统中的作用。

在这项研究中，我们描述了相互关联的神经生理机制，最终导致 4 个月大的小鼠缺乏 NLRP3 炎性体。这些包括以下内容：焦虑行为和学习和记忆的恶化 恐惧条件反射；成人神经发生受损；减少和改变大脑中星形胶质细胞的形态；基底外侧杏仁核 (BLA) 过度兴奋；NLRP3 KO 小鼠 CA1 海马区锥体细胞轴突的激活受损，特别是通过 Schaffer 侧支通路；锥体细胞中突触转导受损，这是由海马 CA3 区突触前位点神经递质释放的尴尬所介导的。

本研究证明了新的发现，即幼鼠大脑中基础水平的 NLRP3 炎性体是条件诱导的腹侧海马和基底外侧杏仁核可塑性所必需的。NLRP3 的缺失会损害突触转导并导致焦虑样行为和费力的恐惧学习，这表明由 NLRP3 表达介导的低度炎症在记忆巩固中起关键作用。