Engineering Exosomes to Specifically Target the Mitochondria of Brain Cells

Yan, Xin; Chen, Xinqian; Shan, Zhiying; Bi, Lanrong

doi:10.1021/acsomega.3c06617

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…Our present study explored the concept that brain-derived EVs can traverse the BBB. By marking these EVs with a mitochondrial-targeted fluorescent dye [ 29 ], we could follow their journey to remote organs, such as the heart and kidneys in rats. This movement was verified by confocal microscopy, providing new insights into how substances originating in the brain might systematically influence other organs, particularly the kidneys.…”

Section: Discussionmentioning

confidence: 99%

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Induction of Neuroinflammation and Brain Oxidative Stress by Brain-Derived Extracellular Vesicles from Hypertensive Rats

Chen,

Yan,

Gingerich

et al. 2024

Antioxidants

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Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt-Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased the mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, the mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

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Section: Discussionmentioning

confidence: 99%

“…Following established protocols, brain-derived EVs were labeled with rhodamine-based fluorophores [ 29 ]. The labeled EVs (Rho-EVs) underwent incubation with primary neuronal cultures.…”

Section: Methodsmentioning

confidence: 99%

Induction of Neuroinflammation and Brain Oxidative Stress by Brain-Derived Extracellular Vesicles from Hypertensive Rats

Chen,

Yan,

Gingerich

et al. 2024

Antioxidants

Self Cite

View full text Add to dashboard Cite

show abstract

“…Following established protocols, brain-derived EVs were labeled with rhodaminebased fluorophores [29]. The labeled EVs (Rho-EVs) underwent incubation with primary neuronal cultures.…”

Section: Fluorescent Labeling Of Brain-derived Evsmentioning

confidence: 99%

Induction of Neuroinflammation and Brain Oxidative Stress by Brain-derived Extracellular Vesicles from Hypertensive Rats

Chen,

Yan,

Gingerich

et al. 2024

Preprint

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Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

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Recent progress in engineered extracellular vesicles and their biomedical applications

Mazahir,

Yadav

2024

Life Sciences

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Engineering Exosomes to Specifically Target the Mitochondria of Brain Cells

Cited by 4 publications

References 27 publications

Induction of Neuroinflammation and Brain Oxidative Stress by Brain-Derived Extracellular Vesicles from Hypertensive Rats

Induction of Neuroinflammation and Brain Oxidative Stress by Brain-Derived Extracellular Vesicles from Hypertensive Rats

Induction of Neuroinflammation and Brain Oxidative Stress by Brain-derived Extracellular Vesicles from Hypertensive Rats

Recent progress in engineered extracellular vesicles and their biomedical applications

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