Department of Anesthesiology, Zhongshan Hospital Fudan University, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, and the Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Department of Anesthesiology, Wusong Hospital Branch, Zhongshan Hospital Affiliated to Fudan University, Shanghai 201999, China.
Sci Adv. 2024 Nov 29;10(48):eadp9413. doi: 10.1126/sciadv.adp9413. Epub 2024 Nov 27.
Peripheral inflammation is closely related to the pathogenesis of sickness behaviors and psychiatric disorders such as anxiety and depression. The circumventricular organs (CVOs) are important brain sites to perceive peripheral inflammatory signals, but few studies have reported their role in inflammation-induced anxiety or depression. Using a mouse model of lipopolysaccharide (LPS)-induced inflammation, we identified a previously unreported role of the subfornical organ (SFO), one of the CVOs, in combating inflammation-induced anxiety. LPS treatment induced anxiety-like and sickness behaviors in mice. Although both the SFO and the organum vasculosum of the lamina terminalis (a CVO) neurons were activated after LPS treatment, only manipulating SFO neurons modulated LPS-induced anxiety-like behaviors. Activating or inhibiting SFO neurons alleviated or aggravated LPS-induced anxiety-like behaviors. In addition, SFO exerted this effect through glutamatergic projections to the bed nucleus of the stria terminalis. Manipulating SFO neurons did not affect LPS-induced sickness behaviors. Thus, we uncovered an active role of SFO neurons in counteracting peripheral inflammation-induced anxiety.
外周炎症与疾病行为和焦虑、抑郁等精神障碍的发病机制密切相关。室周器官（CVOs）是感知外周炎症信号的重要脑区，但很少有研究报道其在炎症引起的焦虑或抑郁中的作用。本研究使用脂多糖（LPS）诱导的炎症小鼠模型，发现了一个之前未被报道的室周下器（SFO）在对抗炎症引起的焦虑中的作用。LPS 处理诱导小鼠出现焦虑样和疾病行为。尽管 LPS 处理后 SFO 和终板血管器官（CVOs）神经元均被激活，但只有操纵 SFO 神经元才能调节 LPS 诱导的焦虑样行为。激活或抑制 SFO 神经元可减轻或加重 LPS 诱导的焦虑样行为。此外，SFO 通过谷氨酸能投射到终纹床核发挥此作用。操纵 SFO 神经元不影响 LPS 诱导的疾病行为。因此，我们揭示了 SFO 神经元在对抗外周炎症诱导的焦虑中的积极作用。
