Neuronal Igfbp2 deficiency in the prefrontal cortex impairs cognition through synaptic dysfunction in male mice.
Overview
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
- Department of Anesthesiology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Department of Gastroenterology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Sacramento, CA 95817, USA
- Ambulatory Surgery Center, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Abstract
Insulin-like growth factor binding protein 2 (Igfbp2) is known to participate in brain development and synaptic regulation, but its specific contribution to prefrontal cortex (PFC)-dependent cognitive function remains unclear. Here, we demonstrate that neuronal Igfbp2 in the PFC plays a critical role in maintaining cognitive performance and synaptic integrity. Neuron-specific Igfbp2 knockdown impaired recognition and spatial memory without altering emotional or locomotor behaviors. Mechanistically, loss of Igfbp2 reduced dendritic spine density, downregulated synapsin-1 and PSD-95 expression, and weakened excitatory synaptic transmission. Remarkably, the local infusion of recombinant Igfbp2 protein restored synaptic architecture and rescued cognitive deficits. Together, these findings identify neuronal Igfbp2 as an essential regulator of PFC-dependent cognition and highlight its potential as a therapeutic target for cognitive dysfunction.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Versions
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Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 3 keywords, 1 funder, 37 references, 12 RRIDs.
Cite
This paper
Zhao, W., Gao, Y., Wang, Y., Peng, K., Song, S., Yang, Y., Zhao, B., Shan, X., Deng, L., Weng, R., Liu, H., Meng, X., Liu, H., & Ji, F. (2026). Neuronal Igfbp2 deficiency in the prefrontal cortex impairs cognition through synaptic dysfunction in male mice. iScience, 29(5), 115629. https://
BibTeX
@article{zhao2026neurona
author = {Zhao, Weiming and Gao, Yanan and Wang, Yichan and Peng, Ke and Song, Shaoyong and Yang, Yufan and Zhao, Baojian and Shan, Xisheng and Deng, Li and Weng, Ruixia and Liu, Hong and Meng, Xiaowen and Liu, Huayue and Ji, Fuhai},
title = {{Neuronal Igfbp2 deficiency in the prefrontal cortex impairs cognition through synaptic dysfunction in male mice}},
journal = {iScience},
year = {2026},
month = apr,
volume = {29},
number = {5},
pages = {115629},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/
url = {https://
pmid = {42058900},
pmcid = {PMC13122697}
}
RIS
TY - JOUR
AU - Zhao, Weiming
AU - Gao, Yanan
AU - Wang, Yichan
AU - Peng, Ke
AU - Song, Shaoyong
AU - Yang, Yufan
AU - Zhao, Baojian
AU - Shan, Xisheng
AU - Deng, Li
AU - Weng, Ruixia
AU - Liu, Hong
AU - Meng, Xiaowen
AU - Liu, Huayue
AU - Ji, Fuhai
TI - Neuronal Igfbp2 deficiency in the prefrontal cortex impairs cognition through synaptic dysfunction in male mice
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/
VL - 29
IS - 5
SP - 115629
SN - 2589-0042
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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