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<p>Exposure to early life adversity (ELA) poses a significant global public health concern, with profound pathophysiological implications for affected individuals. Studies suggest that ELA contributes to endothelial dysfunction, bringing into question the functional integrity of the neurovascular unit in brain regions vulnerable to chronic stress. Despite the importance of the neurovasculature in maintaining normal brain physiology, human neurovascular cells remain poorly characterized, particularly with regard to their contributory role in ELA-associated pathophysiologies. In this study, we present the first comprehensive transcriptomic analysis of microvessels isolated from postmortem ventromedial prefrontal cortex samples from adult healthy controls (CTRL) and matched depressed suicides with histories of ELA. Our findings point to substantial differences between men and women, with the latter exhibiting widespread transcriptional changes at the neurovascular unit, including key vascular nodal regulators <i>KLF2</i> and <i>KLF4</i>, alongside a broad downregulation of immune-related pathways. These results suggest that the neurovascular unit plays a larger role in the neurobiological consequences of ELA in women.</p>

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Pervasive neurovascular dysfunction in the ventromedial prefrontal cortex of female depressed suicides with a history of childhood abuse

  • 期刊论文

  • 发表日期：

    2025年10月30日

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  • Marina Wakid,
  • Daniel Almeida,
  • Ryan Denniston,
  • Anjali Chawla,
  • Zahia Aouabed,
  • Maria Antonietta Davoli,
  • Kristin Ellerbeck,
  • Reza Rahimian,
  • Volodymyr Yerko,
  • Elena Leonova-Erko,
  • Gustavo Turecki,
  • Naguib Mechawar

摘要

Exposure to early life adversity (ELA) poses a significant global public health concern, with profound pathophysiological implications for affected individuals. Studies suggest that ELA contributes to endothelial dysfunction, bringing into question the functional integrity of the neurovascular unit in brain regions vulnerable to chronic stress. Despite the importance of the neurovasculature in maintaining normal brain physiology, human neurovascular cells remain poorly characterized, particularly with regard to their contributory role in ELA-associated pathophysiologies. In this study, we present the first comprehensive transcriptomic analysis of microvessels isolated from postmortem ventromedial prefrontal cortex samples from adult healthy controls (CTRL) and matched depressed suicides with histories of ELA. Our findings point to substantial differences between men and women, with the latter exhibiting widespread transcriptional changes at the neurovascular unit, including key vascular nodal regulators KLF2 and KLF4, alongside a broad downregulation of immune-related pathways. These results suggest that the neurovascular unit plays a larger role in the neurobiological consequences of ELA in women.