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Knock-Down of CD24 in Astrocytes Aggravates Oxyhemoglobin-Induced Hippocampal Neuron Impairment

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A Correction to this article was published on 06 January 2022

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Abstract

Subarachnoid hemorrhage (SAH), as one of the most severe hemorrhagic strokes, is closely related to neuronal damage. Neurogenesis is a promising therapy, however, reliable targets are currently lacking. Increasing evidence has indicated that CD24 is associated with the growth of hippocampal neurons and the regulation of neural stem/precursor cell proliferation. To investigate the potential effect of CD24 in astrocytes on neuron growth in the hippocampus, we used a Transwell co-culture system of hippocampal astrocytes and neurons, and oxyhemoglobin (OxyHb) was added to the culture medium to mimic SAH in vitro. A specific lentivirus was used to knock down CD24 expression in astrocytes, which was verified by western blot, quantitative real-time polymerase chain reaction, and immunofluorescent staining. Astrocyte activation, neurite elongation, neuronal apoptosis, and cell viability were also assessed. We first determined the augmented expression level of CD24 in hippocampal astrocytes after SAH. A similar result was observed in cultured astrocytes exposed to OxyHb, and a corresponding change in SHP2/ERK was also noticed. CD24 in astrocytes was then downregulated by the lentivirus, which led to the impairment of axons and dendrites on the co-cultured neurons. Aggravated neuronal apoptosis was induced by the CD24 downregulation in astrocytes, which might be a result of a lower level of brain derived neurotrophic factor (BDNF). In conclusion, the knock-down of CD24 in astrocytes suppressed hippocampal neuron growth, in which the SHP2-ERK signaling pathway and BNDF were possibly involved.

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Data Availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Code Availability

Not applicable.

Change history

Abbreviations

SAH:

Subarachnoid hemorrhage

OxyHb:

Oxyhemoglobin

BDNF:

Brain derived neurotrophic factor

EBI:

Early brain injury

SVZ:

Subventricular zone

DG:

Dentate gyrus

TBI:

Traumatic brain injury

qPCR:

Quantitative real-time polymerase chain reaction

LV:

Lentiviral vectors

NC:

Negative control

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling

ELISA:

Enzyme-linked immunosorbent assay

DMEM:

Dulbecco’s modified eagle’s medium

FBS:

Fetal bovine serum

CCK8:

Cell counting kit-8

HRP:

Horseradish peroxidase

DAPI:

4,6-Diamidino-2-phenylindole

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Acknowledgements

This work was supported by grants from the Key Project of Medical Science and Technology Development Foundation, Nanjing Department of Health (No. JQX18001 for W. Li), the Natural Science Foundation of Jiangsu Province, China (BK20201113 for W. Li), and the National Natural Science Foundation, China (Nos. 81871122, 81771291 for C.H. Hang, No. 81801166 for Lingyun Wu, No. 81901203 for Yue Lu).

Funding

This study were funded by National Natural Science Foundation of China (Nos. 81871122, 81771291, 81801166, 81901203) and Fundamental Research Funds for the Central Universities (021414380361).

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Author notes

  1. Chen Xiang-Xin and Tao Tao have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China

    Xiang-Xin Chen, Sen Gao, Han Wang, Yong-Yue Gao, Chun-Hua Hang & Wei Li

  2. Department of Neurosurgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China

    Tao Tao

  3. Department of Neurosurgery, The First School of Medicine, Jinling Hospital, Southern Medicine University (Guangzhou), Nanjing, China

    Han Wang

  4. Department of Neurosurgery, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China

    Xiao-Ming Zhou

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  1. Xiang-Xin Chen
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  2. Tao Tao
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  3. Sen Gao
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  4. Han Wang
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  8. Wei Li
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Contributions

XXC performed the studies and wrote the manuscript, TT analyzed and interpreted results, SG participated in the primary cell culture, HW contributed to the western blotting and the ELISA test, XMZ contributed to the immunofluorescent staining and the qPCR test, YYG contributed to the analysis of the data, CH contributed to the study design, and WL contributed to the study design and the critical reversion of manuscript.

Corresponding authors

Correspondence to Chun-Hua Hang or Wei Li.

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The authors declare that they have no competing interests.

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All animal procedures were approved by the Ethics Review Committee for Animal Experimentation at Nanjing Drum Tower Hospital and conformed to the Guide for the Care and Use of Laboratory Animals by the National Institutes of Health.

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Chen, XX., Tao, T., Gao, S. et al. Knock-Down of CD24 in Astrocytes Aggravates Oxyhemoglobin-Induced Hippocampal Neuron Impairment. Neurochem Res 47, 590–600 (2022). https://doi.org/10.1007/s11064-021-03468-x

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