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  11. Disruption Of Cerebral Cholesterol Homeostasis By Ps-nps: Astrocytic Endoplasmic Reticulum Stress.
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  11. Disruption Of Cerebral Cholesterol Homeostasis By Ps-nps: Astrocytic Endoplasmic Reticulum Stress.

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Disruption of cerebral cholesterol homeostasis by PS-NPs: astrocytic endoplasmic reticulum stress.

Lei Tian1, Yizhe Wei1,2, Jianping Ma1

  • 1Military Medical Sciences Academy, Academy of Military Sciences, Tianjin, 300050, China.

Journal of Nanobiotechnology
|December 24, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

Polystyrene nanoplastics (PS-NPs) disrupt brain cholesterol metabolism by inducing endoplasmic reticulum stress in astrocytes. This impairs cholesterol synthesis and transport, ultimately inhibiting neuronal synapse formation and causing neurotoxicity.

Keywords:
AstrocytesCholesterolEndoplasmic reticulum stressNanoplastics

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Area of Science:

  • Neuroscience
  • Toxicology
  • Biochemistry

Background:

  • Cholesterol is vital for synaptic function and brain membrane fluidity.
  • Astrocytes are the primary source of brain cholesterol due to the blood-brain barrier.
  • The impact of polystyrene nanoplastics (PS-NPs) on brain cholesterol metabolism is understudied.

Purpose of the Study:

  • To investigate the effects of PS-NPs on intracranial cholesterol metabolic pathways.
  • To elucidate the mechanisms by which PS-NPs affect astrocyte and neuronal function.
  • To assess the neurotoxic potential of PS-NPs via cholesterol homeostasis disruption.

Main Methods:

  • Whole-brain organoids (WBOs) were exposed to PS-NPs.
  • Whole-transcriptome sequencing was used to analyze pathway changes.
  • A Transwell neuronal-astrocyte co-culture model was employed to study astrocyte-neuron interactions.

    • Main Results:

    • PS-NPs induced endoplasmic reticulum stress and autophagy in astrocytes (elevated ATF4, CHOP, LC3-II/I ratio).
    • PS-NPs inhibited the AKT/ACLY pathway, reducing astrocyte acetyl-CoA and cholesterol.
    • PS-NPs decreased apolipoprotein APOE, hindering cholesterol transport and inhibiting synaptin (SYN) formation.

    Conclusions:

    • PS-NPs induce neurotoxicity by disrupting astrocyte cholesterol homeostasis.
    • Impaired cholesterol synthesis and transport by PS-NPs inhibit neuronal synaptogenesis.
    • Targeting endoplasmic reticulum pathways may restore cholesterol synthesis and neuronal synapses affected by PS-NPs.