Scholarlink

<p>Emerging evidence links glymphatic dysfunction to depression, yet its regulatory mechanisms remain unclear. Through multimodal neuroimaging of two independent cohorts, we tested the hypothesis that the cholinergic basal forebrain (ChBF) modulates glymphatic function and thereby contributes to depression. Glymphatic function was indexed using two indirect MRI markers: the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and coupling between global blood-oxygen-level-dependent signals and cerebrospinal fluid signals (gBOLD-CSF coupling). In a stroke cohort, we explored ChBF-glymphatic-depression interactions through dual perspectives: acute lesion effects and longitudinal recovery. Baseline lesion network mapping analysis (<i>n</i> = 189) revealed that functional connectivity (FC) between ChBF and lesion predicted glymphatic impairment. Longitudinal resting-state fMRI analysis (<i>n</i> = 71) demonstrated that recovery of ChBF whole-brain FC correlated with glymphatic restoration. Glymphatic dysfunction mediated the association between ChBF damage and post-stroke depression severity. Subsequently, we validated these findings in non-stroke cohort (<i>n</i> = 38) receiving transcranial magnetic stimulation. FC between the stimulation site and ChBF predicted glymphatic improvement, with enhanced ChBF whole-brain FC mediating this association. Furthermore, increased ChBF whole-brain FC was correlated with antidepressant efficacy and glymphatic enhancement mediated this relationship. Our findings identify that ChBF play a regulatory role in glymphatic function, which in turn influences depression. This study provides a theoretical foundation for the development of glymphatic-based therapeutic strategies for depression.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Cholinergic basal forebrain modulation of glymphatic function: implications for depression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月21日

查看全文
  • Yirong Fang,
  • Zeyu Lu,
  • Xian Chao,
  • Ran Shi,
  • Dawei Yin,
  • Yanan Lu,
  • Peng Wang,
  • Xinfeng Liu,
  • Wen Sun

摘要

Emerging evidence links glymphatic dysfunction to depression, yet its regulatory mechanisms remain unclear. Through multimodal neuroimaging of two independent cohorts, we tested the hypothesis that the cholinergic basal forebrain (ChBF) modulates glymphatic function and thereby contributes to depression. Glymphatic function was indexed using two indirect MRI markers: the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and coupling between global blood-oxygen-level-dependent signals and cerebrospinal fluid signals (gBOLD-CSF coupling). In a stroke cohort, we explored ChBF-glymphatic-depression interactions through dual perspectives: acute lesion effects and longitudinal recovery. Baseline lesion network mapping analysis (n = 189) revealed that functional connectivity (FC) between ChBF and lesion predicted glymphatic impairment. Longitudinal resting-state fMRI analysis (n = 71) demonstrated that recovery of ChBF whole-brain FC correlated with glymphatic restoration. Glymphatic dysfunction mediated the association between ChBF damage and post-stroke depression severity. Subsequently, we validated these findings in non-stroke cohort (n = 38) receiving transcranial magnetic stimulation. FC between the stimulation site and ChBF predicted glymphatic improvement, with enhanced ChBF whole-brain FC mediating this association. Furthermore, increased ChBF whole-brain FC was correlated with antidepressant efficacy and glymphatic enhancement mediated this relationship. Our findings identify that ChBF play a regulatory role in glymphatic function, which in turn influences depression. This study provides a theoretical foundation for the development of glymphatic-based therapeutic strategies for depression.