Bibliographic Details
| Title: |
Autophagy defects at weaning impair complement-dependent synaptic pruning and induce behavior deficits. |
| Authors: |
Su, Xi1,2,3,4,5 (AUTHOR) suxi198919@163.com, Wang, Guanyu1,3,4 (AUTHOR), Liu, Senqi1,3,4 (AUTHOR), Li, Jinming1,3,4 (AUTHOR), Shao, Minglong1,2,3,4,5 (AUTHOR), Yang, Yongfeng1,2,3,4,5 (AUTHOR), Song, Meng1,2,3,4,5 (AUTHOR), Han, Yong1,2,3,4,5 (AUTHOR), Li, Wenqiang1,2,3,4,5 (AUTHOR), Lv, Luxian1,3,4 (AUTHOR) lvx928@126.com |
| Source: |
Journal of Neuroinflammation. 9/27/2024, Vol. 21 Issue 1, p1-18. 18p. |
| Subject Terms: |
*MATERNAL immune activation, *LABORATORY rats, *SINGLE nucleotide polymorphisms, *DENDRITIC spines, *GENE expression |
| Abstract: |
Autophagy is crucial for synaptic plasticity and the architecture of dendritic spines. However, the role of autophagy in schizophrenia (SCZ) and the mechanisms through which it affects synaptic function remain unclear. In this study, we identified 995 single nucleotide polymorphisms (SNPs) across 19 autophagy-related genes that are associated with SCZ. Gene Set Enrichment Analysis (GSEA) of data from the Gene Expression Omnibus public database revealed defective autophagy in patients with SCZ. Using a maternal immune activation (MIA) rat model, we observed that autophagy was downregulated during the weaning period, and early-life activation of autophagy with rapamycin restored abnormal behaviors and electrophysiological deficits in adult rats. Additionally, inhibition of autophagy with 3-Methyladenine (3-MA) during the weaning period resulted in aberrant behaviors, abnormal electrophysiology, increased spine density, and reduced microglia-mediated synaptic pruning. Furthermore, 3-MA treatment significantly decreased the expression and synaptosomal content of complement, impaired the recognition of C3b and CR3, indicating that autophagy deficiency disrupts complement-mediated synaptic pruning. Our findings provide evidence for a significant association between SCZ and defective autophagy, highlighting a previously underappreciated role of autophagy in regulating the synaptic and behavioral deficits induced by MIA. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Neuroinflammation is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
|
Full text is not displayed to guests. |
Login for full access.
|
