Yan Ning personally invites PI: Professor Danyang\'s sleep research has achieved another breakthrough

  Previously, Academician Yan Ning posted on Weibo to congratulate the first senior PI he invited for returning to China to join the Shenzhen Academy of Medical Sciences. On May 26, 2025, the Shenzhen Academy of Medical Sciences officially announced that Professor Danyang, an academician of the National Academy of Sciences and an academician of the American Academy of Arts and Sciences, will join the institute full-time in June 2025.


  

  As an internationally renowned neuroscientist, Professor Danyang has been deeply engaged in the fields of visual neuroscience and sleep neural mechanisms for many years. His research results have been published in top academic journals such as Cell, Nature Neuroscience, and Science Advanceds, opening up a new perspective for understanding brain functions. Recently, she has published a major research in Cell, so let us focus on its latest scientific research results together.

  Cell

  On June 24, 2025, Professor Danyang's team published a research paper entitled "Neuroendocrine circuit for sleep-dependent growth hormone release" in the top international journal Cell.


  

  Sleep is crucial to the recovery of the body and brain. Deficiency of sleep can cause health problems such as diabetes and obesity, and its impact on tissues and organs is partially achieved through neuroendocrine regulation. Growth hormone (GH) can promote growth and regulate metabolism, while GH deficiency is similar to the adverse consequences of sleep deprivation, and GH release is closely related to sleep, but the neural mechanisms of the interaction between the two have not been elucidated.

  Through optogenetic and chemical genetic techniques, combined with calcium imaging and electrode recording, the research team found that the activity of hypothalamic GHRH and SST neurons in the sleep-awakened state regulates GH release: arcuate nuclear SST neurons inhibit GHRH neurons, and periventricular SST neurons projected to the median bulge, jointly inhibiting GH release, while the activity patterns of GHRH and SST in REM and NREM are different in sleep. In addition, it was found that GH promotes awakening by enhancing the excitability of the locus neurons, revealing the bidirectional neural circuit mechanism of sleep and hormone regulation.



  Science Advances

  

  On January 17, 2025, Professor Danyang's research team published a research paper entitled "Activation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure" in the journal Science Advanceds.

  The study revealed through a series of experiments that the activation of norepinephrine neurons in the locustrine nucleus rapidly triggers sleep homeostasis stress.


  

  Homeostasis regulation of sleep is crucial to maintaining brain recovery function. Its mechanism involves adenosine accumulation, synaptic enhancement, etc., but the specific role of each mechanism in the natural sleep cycle is still unclear. The locustrine nucleus (LC) norepinephrine neurons are key arousal-pro-awakening nerve groups, but whether their activities are involved in the formation of sleep stress through "functional fatigue" has not been systematically studied.

  The research team used optogenetics and fiber optic photometry to find that activating LC neurons can quickly increase sleep tendencies after brief awakening, which is different from other pro-awakening neurons. Repeated stimulation results in a sharp decline in calcium activity and intracerebral norepinephrine (NE) release in LC neurons, while knockdown of α2A adrenergic receptors inhibits this decline and prolongs awakening, confirming that α2A receptor-mediated NE autoinhibition is involved in this process. This study reveals that the “functional fatigue” of LC neurons becomes a new mechanism for the formation of sleep stress by reducing the ability to promote awakening.

  Nature neuroscience

  On January 18, 2024, Professor Danyang's research team published "Microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission" in the journal Nature neuroscience. This study revealed through a series of experiments that microglia regulate sleep through norepinephrine transmission regulation that relies on calcium signal.


  

  Sleep is crucial for the maintenance of brain homeostasis (such as regulation of neuronal activity and removal of metabolic waste), and microglia, as the main immune cells in the brain, play a key role in synaptic pruning and neuroprotection. Both sleep disorders and microglia abnormalities are associated with neurodegenerative diseases, but the interaction mechanism between the two is still unclear. Metabolic substances (such as ATP, adenosine) and cytokines are known to regulate sleep, while microglia-expressed P2Y12 receptor (Gi-coupled GPCR) responds to these molecules, suggesting that they may be involved in sleep regulation.

  The research team used microglia-specifically labeled Tmem119-CreERT2 mice, combined with chemical genetics, two-photon imaging and biosensor technology, to find that microglia regulate sleep through the P2Y12–Gi signaling pathway: activation of this signal can increase the intracellular Ca²⁺ levels, inhibit norepinephrine transmission and increase adenosine concentration, thereby promoting sleep; during natural sleep switching, a decrease in norepinephrine levels will also induce an increase in microglia Ca²⁺. Conversely, blocking P2Y12–Gi signal or Ca²⁺ elevation reduces sleep. This study reveals a new mechanism by which microglia regulate sleep through the interaction of Ca²⁺ signal with the norepinephrine-adenosine system.

  The joining of Academician Danyang has injected strong impetus into the Shenzhen Academy of Medical Sciences in the field of sleep and consciousness research. As the research team led by her in-depth exploration, these cutting-edge research results will not only promote human understanding of the mysteries of the brain, but also hope to bring new dawn to the prevention and treatment of major health problems such as sleep disorders and neurodegenerative diseases, and help my country move to a higher international level in the field of brain science research.