Research

Neuroscience, immune, and neurodegeneration

Neurodegeneration and Neuroimmunity

Glial Dynamics and Phagocytosis in Neuronal Decline

Microglia and astrocytes are central to the pathogenesis of neurodegenerative diseases. We investigate how these glial populations cooperatively detect, engulf, and clear degenerating neurons, and how astrocytic reactivity influences neuronal survival. While this highly regulated phagocytic process is essential for tissue cleanup, it is frequently accompanied by the release of proinflammatory signals. Our research aims to decode how these coordinated glial behaviors dictate the balance between neuroprotection and neurotoxicity, ultimately influencing the progression and resolution of neurodegenerative conditions.

Stress, Emotion, and Glial Networks

Glial Sensing and the Regulation of Affective States

Microglia and astrocytes act as active environmental sensors in the brain, responding to stress-induced signals, neurotransmitters, and stress hormones such as norepinephrine and cortisol. By dynamically monitoring neuronal activity, clearing neurotransmitters, and remodeling synapses, these glial cells directly interact with neural circuits governing emotion. We explore how this neuro-glial crosstalk not only detects physiological and psychological stress but fundamentally modulates emotional homeostasis, resilience, and susceptibility to affective disorders.

Metabolic Interventions and Cognitive Function

Harnessing Intermittent Fasting for CNS Resilience and Healthy Aging

Intermittent fasting (IF) induces profound systemic metabolic shifts, such as the transition from glucose to ketone utilization. Astrocytes, as the primary metabolic hubs of the brain, play a critical role in mediating these energetic transitions. Our research investigates how these metabolic adaptations enhance cellular stress resistance, suppress neuroinflammation, and modulate central nervous system (CNS) homeostasis. By uncovering the mechanisms through which IF regulates both astrocytic and microglial activity to promote neural plasticity, we aim to translate metabolic interventions into therapeutic strategies that support healthy aging.

Anesthesia and Immune Network Dynamics

Decoding the Impact of Anesthetics on Central and Peripheral Immunity

The direct pharmacological effects of general anesthesia on central and peripheral immune cells remain a critical gap in perioperative medicine. We investigate how anesthetic agents perturb neuro-immune interactions, alter microglial states, and trigger systemic inflammatory responses. Uncovering these specific cellular targets is essential for understanding anesthesia-induced alterations in consciousness and mitigating severe clinical complications, such as postoperative cognitive dysfunction (POCD) and immune suppression.

Microglial Homeostasis and Heterogeneity

Intrinsic Regulatory Networks Governing Glial States

Microglial homeostasis involves intrinsic mechanisms that regulate their surveillance, activation states, and self-renewal, including the control of cell density. This ensures balanced responses to environmental cues. Population heterogeneity reflects diverse transcriptional and functional states across subsets, enabling context-specific adaptation and preserving neural integrity throughout different brain regions and conditions.

Technique

Featured approaches

Two-photon in vivo imaging

Enhanced by lab-innovated devices, to monitor long-term changes of the brain.

Electrophysiology

Whole-cell patch-clamp techniques in brain slices allow us to explore the brain's health and disease states, from ion channel function to synaptic transmission mechanisms.

Imaging guided patch-seq

Spatial and temporal RNA-seq on targeted cells of interest to analyze gene expression dynamics.

Publication

Selected (#first author, *corresponding author)

Recent

2026

  • Zhang G#, Meng W#, Xu LJ#, Mou B, Xiang Z, Ruan X, Liu YU*, Shu H*. In Vivo Imaging of Neuronal Activity Shifts in the Somatosensory Cortex After Morphine Tolerance in Mice. Addict Biol., 2026 Apr;31(4):e70155. doi: 10.1111/adb.70155.
  • Wu J, Lu X, Zhang J, Wang S, Lu Z, Han Y, Yang R, Su Y, Tan C, Huo D, Liu YU*, Sima J*. Astrocytic AEBP1-NPAS3-LIPA pathway coordinates cholesterol homeostasis to regulate Alzheimer's pathology. Cell Rep., 2026 Mar 24;45(4):117193. doi: 10.1016/j.celrep.2026.117193.
  • Gu Y, Zhang L, Du Z, Wang C, Deng W, Liu YU*, Tang B*. Aging of the Blood-Brain Barrier and Altered Permeability to Peripheral Immune Cells: Implications for Central Nervous System Disorders. Aging Dis., 2026 Feb 16. doi: 10.14336/AD.2026.0013. 

2025

  • Bu S#, Mou B#, Xiang Z#, Zhang L, Hao B, Chen J, Huang L, Ruan X, Liu YU*, Zhang Y*. Hyperglycemia impairs microglia responding to retinal vasculopathy via enhanced norepinephrine-ADRB2 signaling. J Neuroinflammation., 2025 Dec 8;23(1):14. doi: 10.1186/s12974-025-03647-5.

2024

  • Xia Wang#, Han Zhan#, Bin Mou, Libo Hua, Zheng Zhao, Lang Huang, Jian Sima, Zongqin Xiang*, Yong U. Liu*. Chronic in vivo imaging of tau-induced neurodegeneration and microglial response using two-photon microscopy. Aging Research, 2024, 2(3): 9340035. DOI: 10.26599/AGR.2024.9340035
  • Zheng Zhao#, Jun-Liang Chen#, Han Zhan, Chang-Rong Fang, Li-Bo Hua, Hao-Yuan Deng, Zongqin Xiang, Ying Yang, Lang Huang*, Yong U Liu*. Noradrenergic projections from the locus coeruleus to the medial prefrontal cortex enhances stress coping behavior in mice following long-term intermittent fasting. Neuromolecular Medicine, 2024. 26, 47. DOI: 10.1007/s12017-024-08818-w

Previous

2021

  • Manling Xie# , Yong U. Liu*#, Shunyi Zhao, Lingxin Zhang, Dale B. Bosco, Yuan-Ping Pang, Jun Zhong, Udit Sheth, Yuka A. Martens, Na Zhao, Chia-Chen Liu, Yongxian Zhuang, Liewei Wang, Dennis W. Dickson, Mark P. Mattson, Guojun Bu, Long-Jun Wu*. TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP-43-related neurodegeneration. Nature Neuroscience, 2021, Dec 16.

2019

  • Yong U. Liu, Yanlu Ying, Yujiao Li, Ukpong B. Eyo, Tingjun Chen, Jiaying Zheng, Anthony D. Umpierre, Jia Zhu, Dale B. Bosco, Hailong Dong, Long-Jun Wu*. Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling. Nature Neuroscience, 2019, 22:1771–1781.
  • Yong Liu*#, Aiwu Cheng#, Yu-Jiao Li, Ying Yang, Yuki Kishimoto, Shi Zhang, Yue Wang, Ruiqian Wan, Sophia M. Raefsky, Daoyuan Lu, Takashi Saito, Takaomi Saido, Jian Zhu, Long-Jun Wu, Mark P. Mattson*. SIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice. Nature Communications, 2019. 10(1):1886.

2017

  • Yong Liu#, Li-Jun Zhou#, Jun Wang#, Dai Li, Wen-Jie Ren, Jiyun Peng, Xiao Wei, Ting Xu, Wen-Jun Xin, Rui-Ping Pang, Yong-Yong Li, Zhi-Hai Qin, Madhuvika Murugan, Mark P Mattson, Long-Jun Wu*, Xian-Guo Liu*. TNF-α differentially regulates synaptic plasticity in the hippocampus and spinal cord by microglia-dependent mechanisms after peripheral nerve injury. Journal of Neuroscience, 2017. 37(4):871-881.

Member

Current

Liu, Yong U.

Liu, Yong U.

PhD, LNHD 2020-

Principal Investigator, two-photon imaging, whole-cell patch, animal behavior

Huang, Lang

Huang, Lang

PhD, LNHD 2022-

Principal Investigator, Electrophysiology, Patch-seq, Animal behavior

Xiang, Zongqin

Xiang, Zongqin

PhD, LNHD 2022-

Research Scientist, Two-photon imaging, Animal behavior

Ye, Jinfeng

Ye, Jinfeng

BS, LNHD 2023-

Lab manager

Wang, Xia

Wang, Xia

PhD, LNHD 2022-

Two-photon imaging, Biochemistry, Animal behavior

Han, Jianbang

Han, Jianbang

MD, PhD, LNHD 2024-

Two-photon imaging, Cell culture

Mou, Bin

Mou, Bin

PhD student - Postdoc, 2022-

Animal behavior, Immunohistochemistry

Sun, Kaijian

Sun, Kaijian

MD, PhD, LNHD 2024-

Bioinformatics, Residency standardization training in Neurosurgery

Cao, Haihong

Cao, Haihong

PhD student, SYSU, 2023-

Cell culture, Immunohistochemistry

Hua, Libo

Hua, Libo

PhD student, 2023-

Animal behavior, Immunohistochemistry

Chen, Junliang

Chen, Junliang

PhD student, 2024-

Animal behavior, Immunohistochemistry

Zhao, Zheng

Zhao, Zheng

PhD student, SYSU, 2025-

Animal behavior, Immunohistochemistry

Zhang, Liting

Zhang, Liting

MS-PhD student, 2023-

Bioinformatics

Gu, Yu

Gu, Yu

PhD student, 2026-

MDMI and monocyte, Cell culture

Li, Miaoting

Li, Miaoting

MS student, 2024-

Immunohistochemistry, Animal behavior

Deng, Haoyuan

Deng, Haoyuan

MS student, 2024-

Immunohistochemistry, Animal behavior

Du, Zixin

Du, Zixin

PhD student, 2025-

Bioinformatics

Wang, Caiyun

Wang, Caiyun

PhD student, 2025-

MDMI and anesthesia, Cell culture

Chen, Luo

Chen, Luo

MS student, 2025-

Animal behavior

Chen, Zishun

Chen, Zishun

MS student, 2025-

Bioinformatics

Lab Alumini

  • Zhang, Yaping, MS student, 2022-2026
    Current: Residency standardization training in Psychiatry at the Affiliated Brain Hospital of Guangzhou Medical University

  • Deng, Wenyuan, MS student, SYSU, 2023-2026
    Current: Residency standardization training in Anesthesiology at the Sixth Affiliated Hospital, SYSU

  • Fang, Changrong, MS, MS student, 2022-2025

  • Zhan, Han, MS, MS student, 2022-2025

  • Ling, Jiangyue, MS, MS student, 2024-2025

  • Bu, Shimiao, MS, MS student, 2021-2024
    Current: Residency standardization training in Ophthalmology at Guangzhou First People's Hospital

  • Liang, Jiade, MS, Research assistant, 2023-2024
    Current: MS, PhD student at Hainan University

  • Zhang, Renyue, MS, MS student, 2021-2024
    Current: MS, Research assistant at Guangzhou First People's Hospital

  • Miao, Tianze, Research assistant, 2022-2023

  • Xie, Tao, MS, Research assistant, 2021-2022
    Current: PhD student at University of Technology Sydney

Collaborator

Intramural (Clinician)

  • Zhang, Yuehong, MD, PhD, Ophthalmologist, Diabetic retinopathy

  • Zheng, Bin, MD, PhD, Anesthesiologist, Cognitive function

  • Ying, Yanlu, MD, PhD, Anesthesiologist, Neuro-immune interaction

  • Lu, Chengxiang, MD, Anesthesiologist

Intramural

  • Zheng, Jiajun, PhD, Research Scientist, Electrophysiology in vivo and in vitro, Animal behavior

  • Liu, Yufeng, PhD, Principal investigator, Immunologist

Extramural

  • Zhang, Guangyan, MD, Anesthesiologist, Morphine tolerance