医学创新论坛第19期

Time：2:30 PM, March 28, 2024 (Thursday)

Location: Room 1322, North Tower, Basic Research Building, Capital Medical University (首都医科大学基础科研楼北楼1322会议室)

Host: Lin Mei

     Chinese Institutes for Medical Research, Beijing

Speaker: Zhihua Gao (高志华) Professor

Zhejiang University School of Brain Science and Brain Medicine

Title: The roles and features of microglia in the brain: the expected and unexpected

Abstract:

Microglia are the primary resident immune cells in the brain that help to maintain brain homeostasis and modify disease onset and progression. They continuously survey the brain parenchyma with their dynamic processes, and rapidly respond to brain insults. How microglial dynamics is orchestrated by bioenergetic and metabolic mechanisms remains largely unknown. We found that microglia possess a distinct cluster of metabolic genes and identified a key glycolytic enzyme, hexokinase 2 (HK2) specifically expressed in microglia. While HK2 is known to drive glycolysis in muscles to support rapid energy supply during exercise, I will present data regarding how HK2 shapes microglial dynamics and function through metabolic and non-metabolic mechanisms.  

Despite their immune identity, microglia have also been shown to play non-immune roles in the brain. Recently, we have provided the first evidence that microglia are actively engaged in the regulation of general anesthesia (GA). GA is a reversible state of unconsciousness, analgesia, amnesia, and immobility induced by anesthetics. It is well-known that general anesthetics act on specific receptors or channels of neurons to generate such effects. However, we found that microglia are also actively engaged in the modulation of anesthesia. Microglial ablation substantially reduced anesthetic sensitivity and promoted early anesthetic emergence, revealing unexpected functions of microglia in a pharmacologically-induced state. I will summarize these discoveries and introduce potential mechanisms underlying the role of microglia in anesthesia.

Selected publications:

1. Cao K, Qiu L, Xuan Lu X, HuY, Wu W, Chao Jiang C, Shao Y, Wang Xi W, Duan S*, Gao Z*. Microglia modulate general anesthesia through P2Y₁₂ receptor signaling. Cur Biol. 2023 Jun 5;33(11):2187-2200.e6.
2. Hu Y, Cao K, Wang F, Wu W, Mai W, Qiu L, Luo Y, Ge W, Sun B, Shi L, Zhu J, Zhang J, Wu Z, Xie Y, Duan S*,Gao Z*. Dual roles of hexokinase 2 in shaping microglial function by gating glycolytic flux and mitochondrial activity. Nat Metab. 2022 Dec;4(12):1756-1774.
3. ZhangB, Qiu L, Xiao W, Ni H, Chen L, Wang F, Mai W, Wu J, Bao A, Hu H, Gong H, Duan S, Li A*, Gao Z*. Reconstruction of the Hypothalamo-Neurohypophysial System and Functional Dissection of Magnocellular Oxytocin Neurons in the Brain. Neuron. 2021 Jan 20;109(2):331-346.e7.

个人简介：高志华，浙江大学脑科学与脑医学学院与教育部脑与脑机融合前沿科学中心教授，博士生导师，浙江省万人计划科研领军人才，浙江省神经科学学会秘书长，中国生理学会理事，Neuroscience Bulletin编委。长期致力于神经内稳态（神经免疫与神经内分泌）调控在大脑中的生理病理作用与机制研究。近5年以通讯作者在领域内知名学术期刊，如Neuron（ESI高被引论文）、Nature Metabolism、Brain、Current Biology、Cell Reports等发表论文，研究成果被同行广泛引用和正面评述。