40Hz闪光：腺苷假说和转化意义40Hz闪光：腺苷假说和转化意义 40Hz光闪烁已被认为是一种有前景的非侵入性神经调控策略，可用于缓解神经精神疾病。然而，缺乏神经化学基础的研究阻碍了其治疗方法的开发。鉴于40Hz闪烁刺激后腺苷生成与伽马振荡之间存在内在关联，我们提出并验证了以下发现：40Hz光闪烁能够以频率依赖性方式触发初级视觉皮层（V1）细胞外腺苷水平的即时且持续性升高。我们进一步揭示了细胞外腺苷生成的细胞来源（即谷氨酸能和GABA能神经元）及分子通路（即AMPK相关能量代谢通路和平衡型核苷转运体2（ENT2）介导的腺苷外排）。鉴于腺苷在调节神经递质和脑功能中的关键作用，40Hz闪烁的腺苷假说对于开发神经精神疾病的非侵入性治疗具有重要的转化意义。在本次报告中，我还将重点探讨40Hz光闪烁在调节类淋巴系统活性、睡眠调控及缺血性神经元损伤神经保护方面的转化潜力。
40Hz light flickering has emerged as a promising non-invasive neuromodulation strategy to alleviate neuropsychiatric disorders. However, the lack of a neurochemical underpinning has hampered its therapeutic development. As there is an intrinsic relationship of adenosine production and gamma oscillation after 40Hz flickering, we proposed and demonstrated that 40Hz light flickering frequency-dependently triggered an immediate and sustained increase in extracellular adenosine levels in the primary visual cortex (V1). We further uncovered the cellular source (i.e. glutamatergic and GABAergic) neurons) and molecular pathway (i.e. AMPK-associated energy metabolism pathways and adenosine efflux by equilibrative nucleoside transporter-2, ENT2) for extracellular adenosine generation. Given the critical role of adenosine in modulating neurotransmitters and brain functions, the adenosine hypothesis of 40Hz flickering has important translational implications in developing non-invasive treatment for neuropsychiatric disorders. In the talk, I will also highlight the translational potential of 40Hz light flickering in modulating glymphatic activity, sleep regulation and neuroprotection against ischemic neuronal injury. |