Evidence map›Paper›PMID 43020960›Full record

ArticleMolecular neurobiology2026

Microglial Metabolic Reprogramming Regulated by HIF-1α/HK2 Positive Feedback Inhibits Adult Hippocampal Neurogenesis in Diabetes-Associated Cognitive Dysfunction.

Siyu Jiang, Yuanyuan Zhao, Qi Zhang, Jingjing Zhang, Zhaoyu Gao, Yang Luo, Na Zhao, Na Guo, Cuixia An, Rui Zhang and 2 more

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Siyu Jiang *Central Laboratory, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang, 050031, P. R. China.
Yuanyuan Zhao *Central Laboratory, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang, 050031, P. R. China.
Qi Zhang *Central Laboratory, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang, 050031, P. R. China.
Jingjing ZhangNursing Department, The Third Hospital of Qinhuangdao, Qinhuangdao, 066000, P. R. China.
Zhaoyu GaoCentral Laboratory, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang, 050031, P. R. China.
Yang LuoCentral Laboratory, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang, 050031, P. R. China.
Na ZhaoCentral Laboratory, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang, 050031, P. R. China.
Na GuoCentral Laboratory, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang, 050031, P. R. China.
Cuixia AnMental Health Center, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, P. R. China.
Rui ZhangCentral Laboratory, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang, 050031, P. R. China. zhangrui1981@hebmu.edu.cn.
Zanchao LiuHebei Provincial Key Laboratory of Basic Medicine for Diabetes, The Shijiazhuang Second Hospital, Shijiazhuang, 050057, P. R. China. liuzanchao2007@163.com.
Shunjiang XuCentral Laboratory, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang, 050031, P. R. China. xushunjiang@hebmu.edu.cn.

Funding

First Hospital of Hebei Medical University XH202401First Hospital of Hebei Medical University ZF2025043Hebei Provincial Natural Science Foundation H2024206245Hebei Provincial Natural Science Foundation H2024206280
6 · The paper itself

Abstract

Diabetes-associated cognitive dysfunction (DACD) is a significant complication with few effective treatments and unclear underlying mechanism. The aim of this study was to investigate how hyperglycemia disrupts adult hippocampal neurogenesis (AHN) through metabolic-immune interactions, seeking to identify potential treatment targets for DACD. DACD models were developed using db/db mice or streptozotocin-induced mice, and their cognitive function was assessed through behavioral tests. Next, we integrated multi-omics analyses (transcriptomic, single-cell, and lactylome profiling) with metabolic studies in BV2 cells exposed to diabetic conditions. Pharmacological modulators (3-BP, C646, TSA) were used to clarify the underlying mechanisms. The mice with DACD demonstrated cognitive deficits, impaired AHN, and activation of hippocampal microglia. Transcriptomic analysis revealed glycolysis as the primary dysregulated pathway. Mechanistically, hyperglycemia/AGEs induced glycolytic reprogramming and increased lactate levels, which promoted HIF-1α lactylation at lysine residues-a modification catalyzed by p300 and opposed by histone deacetylases. This posttranslational modification was associated with HIF-1α stabilisation and with enhanced transcriptional occupancy at the HK2 promoter. This established a self-amplifying feedback loop, perpetuating microglial activation and disrupting the blood-brain barrier via CXCL10 secretion, which led to CD8

Indexed as

Cognitive DysfunctionDiabetes Mellitus, ExperimentalFeedback, PhysiologicalHippocampusHypoxia-Inducible Factor 1, alpha SubunitMetabolic ReprogrammingMicrogliaNeurogenesisAnimalsGlycolysisMaleMiceMice, Inbred C57BLHypoxia-Inducible Factor 1, alpha SubunitDiabetic-associated cognitive dysfunctionGlycolysisHexokinaseHypoxia-inducible factor 1-alphaLactylation

Identifiers

PMID43020960

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.