Early-life inﬂammation promotes depressive symptoms in adol

AAV-hM4D(Gi) and AAV- hM3D(Gq) were used for chemogenetic manipulation. AAV-GCaMP6f was used for 2P calcium imaging experiments. AAV-GCaMP6m was used for fiber photometry recording. Custom-Made AAVs were used for knockdown and overexpression experiments. (From BrainVTA)

The viruses used in this article from BrainVTA are in the table below

Chemogenetics	PT-0043 rAAV-Ef1α-DIO-hM4D(Gi)-mCherry-WPRE-pA PT-0042 rAAV-Ef1α-DIO-hM3D(Gq)-mCherry-WPRE-pA
Control	PT-0013 rAAV-Ef1α -DIO-mCherry-WPRE-pA PT-0473 rAAV-CAG-DIO-mCherry-WPREs PT-0310 rAAV-CMV-DIO-EGFP-WPRE-hGH pA
CRE Recombinase	PT-0220 rAAV-CaMKIIα-Cre-WPRE-hGH-pA
Calcium sensors	PT-0283 rAAV-EF1α-DIO-GCaMP6m-WPRE-hGH-pA PT-0119 rAAV-CaMKIIα-GCaMP6f-WPRE-hGH pA
Custom-Made AAVs	rAAV-U6-Loxp-CMV-EGFP-Loxp-scramble-shRNA -SV40 pA rAAV-CMV-DIO-CX3CR1-2a-EGFP-WPRE-hGH pA rAAV-U6-Loxp-CMV-EGFP-Loxp-CX3CR1-shRNA-SV40 pA

Peng Cao, Changmao Chen, An Liu, Qinghong Shan, Xia Zhu, Chunhui Jia, Xiaoqi Peng, Mingjun Zhang, Zahra Farzinpour, Wenjie Zhou, Haitao Wang, Jiang-Ning Zhou, Xiaoyuan Song, Liecheng Wang, Wenjuan Tao, Changjian Zheng, Yan Zhang, Yu-Qiang Ding, Yan Jin, Lin Xu, Zhi Zhang
Pub Date: 2021-07-06, DOI: 10.1016/j.neuron.2021.06.012, Email: sales@brainvta.com

Early-life inflammation increases the risk for depression in later life. Here, we demonstrate how early-life inflammation causes adolescent depressive-like symptoms: by altering the long-term neuronal spine engulfment capacity of microglia. For mice exposed to lipopolysaccharide (LPS)-induced inflammation via the Toll-like receptor 4/NF-κB signaling pathway at postnatal day (P) 14, ongoing longitudinal imaging of the living brain revealed that later stress (delivered during adolescence on P45) increases the extent of microglial engulfment around anterior cingulate cortex (ACC) glutamatergic neuronal (ACCGlu) spines. When the ACC microglia of LPS-treated mice were deleted or chemically inhibited, the mice did not exhibit depressive-like behaviors during adolescence. Moreover, we show that the fractalkine receptor CX3CR1 mediates stress-induced engulfment of ACCGlu neuronal spines. Together, our findings establish that early-life inflammation causes dysregulation of microglial engulfment capacity, which encodes long-lasting maladaptation of ACCGlu neurons to stress, thus promoting development of depression-like symptoms during adolescence.

Figure 1. Schematic illustration of ﬁber photometry recording in vivo and representative images validate GCaMP6m expression in glutamatergic neurons and optical ﬁber tract above the ACC.

Early-life inﬂammation increases the risk for depression in later life. In this study, the authors identified that the dysregulation of microglial engulfment capacity after early-life inﬂammation encodes long-lasting maladaptation of ACC^Glu neurons to stress events, which promotes the development of depressive symptoms during adolescence.

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