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Advanced Neurology Proteomic analysis of microglia exosomes

which jointly promote neutrophilic infiltration into the two or more cell types, such as the interplay of exosomes
brain. However, the levels of other chemotactic molecules between microglia and endothelial cells, to improve the
did not differ in the exosomes secreted by microglia understanding of the in vivo milieu.
among the groups, suggesting that they may act on target This study has several limitations. First, we described and
cells through direct secretion. Recent research from our compared the impacts of exosomes secreted by microglia
team has shown that complement pathway activation of different phenotypes on neuronal injury caused by
promotes the inflammatory response of microglia, ischemia in both in vivo and in vitro models, without delving
potentially leading to abnormal synaptic phagocytosis further into the functions of specific exosomal proteins.
and subsequent synaptic impairment. The current study This aspect will be addressed in the forthcoming research.
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revealed increased expression of C3 and CFB in M1-EXOs, Second, we used LPS and IL-4 as stimulants to obtain pure
suggesting the need for further exploration of their roles in M1- and M2-type microglia, following a similar approach
the context of ischemic stroke. seen in other studies, thereby simplifying the complex
The expression of SRGN, a proteoglycan, is elevated in vivo environment, but we might inadvertently overlook
in microglia in vivo and in vitro cerebral ischemia crucial phenomena and mechanisms that necessitate
models. This increase in SRGN expression facilitates the validation and further exploration in subsequent in vivo
microglia-mediated inflammatory response. Suppression experiments. Furthermore, we employed a tMCAO model
of the expression of SRGN or its receptor CD44 effectively instead of a permanent MCAO model (pMCAO) and
mitigates the inflammatory response and reduces ischemic solely observed brain injury during the acute phase after
brain injury. The findings of our study align with this ischemia. In the future, experiments involving more than
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observation. Notably, the expression of SRGN in exosomes two cerebral ischemia models and observing prolonged
released by proinflammatory M1 microglia significantly brain damage must be conducted. Last, investigating the
surpassed that in the other groups. This finding implies that effects of cotreatment with exosomes derived from two
SRGN may also exert its effects on other nerve cells through different microglial phenotypes should also be a priority
exosomes. In addition, the levels of SPP1, a multifunctional for future research.
glycoprotein, are elevated in the cerebrospinal fluid 5. Conclusion
and plasma of Alzheimer’s disease (AD) patients. These
elevated levels drive microglia toward the phagocytosis In this study, we induced microglia to differentiate into two
of synapses, leading to synaptic degeneration. Conversely, distinct phenotypes and isolated their exosomes for both
knockout of the Spp1 gene effectively inhibits this process, in vivo and in vitro experiments. Our findings revealed that
thereby reducing nervous system damage. In our study, M1-EXOs contribute to neuronal apoptosis and exacerbate
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we observed a substantial decrease in SPP1 expression brain injury following ischemia, whereas M2-EXOs
among exosomal proteins derived from both M1-type play a protective role in brain function. The quantitative
and M2-type microglia. This finding suggested that SPP1 proteomics analysis indicated that proteins within
functions differently in ischemic stroke than in AD. M1-EXOs are primarily associated with inflammatory,
chemotactic, and complement-related signaling
Numerous studies have explored the impact of pathways, while proteins in M2-EXOs are involved in cell
exosomes from various cellular origins on safeguarding proliferation and protein transport. These results provide
the brain by inhibiting the activation and inflammation valuable insights for future fundamental research on the
of microglia. For instance, OGD/R-treated HBMVECs role of microglia in various neurological diseases.
transmit circ_0000495 through exosomes to regulate
the miR-579-3p/TLR4/NF-κB axis in microglia, thereby Acknowledgments
promoting microglial M1-type polarization and ultimately
aggravating brain injury. Neural stem cells inhibit the None.
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m6A methylation of microglial NRF2 by transferring the Funding
exosomal FTO protein to microglia, thereby promoting
the transition of microglia from the M1 phenotype to the This research was supported by the National Natural
M2 phenotype. Bone marrow MSC-derived exosomal Science Foundation of China (82371326, 82171310),
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miR-148-3p and miR-23a-3p can suppress abnormal Jiangsu Provincial ‘333’ High-level Talent Training Project
microglial activation induced by cerebral ischemia in vivo Funding.
and OGD/R in vitro. 21,35 Hence, forthcoming investigations
should not solely concentrate on a single source of Conflict of interest
exosomes but should also consider the interplay between The authors declare no conflicts of interest.

Volume 3 Issue 3 (2024) 12 doi: 10.36922/an.3166