Center for Applied Neuroscience, University Hospital (HU), UFSC, Florianopolis, SC, Brazil.
Graduate Program in Neuroscience, UFSC, Florianopolis, SC, Brazil.
Mol Neurobiol. 2021 Apr;58(4):1859-1870. doi: 10.1007/s12035-020-02272-y. Epub 2021 Jan 6.
The central autonomic network, which is connected to the limbic system structures including the amygdala (AMY) and anterior hippocampus (aHIP), regulates the sympathetic and parasympathetic modulation of visceromotor, neuroendocrine, pain, and behavior manifestations during stress responses. Heart rate variability (HRV) is useful to estimate the cardiac autonomic tone. The levels of phosphorylation on the Ser831 and Ser845 sites of the GluA1 subunit of the AMPAr (P-GluA1-Ser845 and P-GluA1-Ser831) are useful markers of synaptic plasticity. The relation between synaptic plasticity in the human limbic system structures and autonomic regulation in humans is unknown. This study investigated the association between HRV and neurochemistry biomarkers of synaptic plasticity in AMY and aHIP. HRV indices were obtained from the resting state electrocardiogram of patients with drug-resistant mesial temporal lobe epilepsy (MTLE, n = 18) and the levels of P-GluA1-Ser845 and P-GluA1-Ser831 in the AMY and aHIP resected during the epilepsy surgery. A backward stepwise multiple linear regression models were used to analyze the association between HRV and synaptic plasticity biomarkers controlling for imbalances in the distribution of sociodemographic, clinical, neuroimaging, and neurosurgical variables. P-GluA1-Ser845 levels in AMY show a negative association (p < 0.05) with the 3 investigated parasympathetic autonomic HRV indices (SDNN, rMSSD, and HF) predicting 24 to 40% of their variation. The final multiple linear regression models include disease duration and levels of P-GluA1-Ser845 and predict 24 to 56% of cardiac autonomic tone variation (p < 0.01). P-GluA1-Ser845 levels in AMY and aHIP are negatively associated with the resting HRV in MTLE-HS indicating that increased synaptic efficiency in amygdala is associated with a parasympathetic cardiac autonomic tone impairment. The results suggest that specific changes in synaptic plasticity may be involved in the brain-heart axis regulation by the limbic system.
中央自主神经网络与包括杏仁核 (AMY) 和前海马体 (aHIP) 在内的边缘系统结构相连，调节自主神经对内脏运动、神经内分泌、疼痛和应激反应期间行为表现的调制。心率变异性 (HRV) 可用于评估心脏自主神经张力。GluA1 亚基 AMPAr 的丝氨酸 831 位和丝氨酸 845 位磷酸化水平 (P-GluA1-Ser845 和 P-GluA1-Ser831) 是突触可塑性的有用标志物。人类边缘系统结构中的突触可塑性与自主调节之间的关系尚不清楚。本研究调查了 AMY 和 aHIP 中 HRV 与突触可塑性神经化学标志物之间的关系。从耐药性内侧颞叶癫痫 (MTLE，n=18) 患者的静息心电图中获得 HRV 指数，并从癫痫手术中切除的 AMY 和 aHIP 中获得 P-GluA1-Ser845 和 P-GluA1-Ser831 水平。使用向后逐步多元线性回归模型，控制社会人口统计学、临床、神经影像学和神经外科学变量分布的不平衡，分析 HRV 与突触可塑性生物标志物之间的关联。AMY 中的 P-GluA1-Ser845 水平与 3 种研究的副交感自主 HRV 指数 (SDNN、rMSSD 和 HF) 呈负相关 (p<0.05)，可预测其 24%至 40%的变化。最终的多元线性回归模型包括疾病持续时间和 P-GluA1-Ser845 水平，并可预测心脏自主神经张力变化的 24%至 56% (p<0.01)。MTLE-HS 中 AMY 和 aHIP 中的 P-GluA1-Ser845 水平与静息 HRV 呈负相关，表明杏仁核中突触效率的增加与副交感心脏自主神经张力受损有关。结果表明，边缘系统调节的脑心轴中可能涉及特定的突触可塑性变化。
