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Извлечено: 997 / 997 (100.0%) Средняя confidence: 0.13
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Metformin improves the impairment of cognitive function caused by total abdominal irradiation via the miR-34a-5p/BDNF/CREB axis.

PMID: 41559494 · DOI: 10.1007/s12035-026-05696-0 · Molecular neurobiology, 2026 · Jianyu Wang, Juan Guo, Li Guo, Qiaohui Gao, Shengyuan Jiao, Xia Miao, Fei Da, Junye Liu
📄 Abstract

The gastrointestinal system is of particular importance in radiation biodosimetry because of its constant cell renewal and sensitivity to radiation-induced injury. It has been reported that total abdominal irradiation causes distant cognitive defects in a mouse model. In this study, we demonstrated that metformin alleviated the cognitive dysfunction caused by total abdominal irradiation. No neuropathological changes were observed in hippocampal tissues in control, irradiated, and irradiated plus metformin-treated groups. However, we found that metformin treatment improved the expression of brain-derived neurotrophic factor and the phosphorylation level of cAMP response element-binding in the hippocampus from irradiated mice. Furthermore, our results revealed that metformin treatment reduced the expression of miR-34a-5p, which targets the brain-derived neurotrophic factor mRNA, in the small intestine, peripheral blood, and hippocampus. More importantly, injection of miR-34a-5p agomir inhibited the enhancement effects of metformin on the cognitive defects induced by total abdominal irradiation, as well as the enhanced expression of BNDF and the phosphorylation level of cAMP response element-binding in the hippocampus. Thus, our results provide alternative strategies for the treatment of total abdominal irradiation-induced distant cognitive impairment using metformin and further confirmed that miR-34a-5p is a potential drug target to reduce the cognitive defects caused by total abdominal irradiation.

Confidence: 0.14 · 7 полей извлечено
Идентификация (6 полей)
Target
miR-34a-5p
0.90
Alt. target
0.00
Protein family
0.00
Functional class
0.00
Subcellular loc.
0.00
Isoforms (metab/obesity)
0.00
Механизм действия (21 полей)
Mechanism
0.00
Mutations (obesity/lean)
0.00
Activity (obesity)
0.00
Activity temporal
0.00
Energy balance
0.00
Appetite
0.00
Fat metabolism
0.00
Lipolysis
0.00
Thermogenesis
0.00
Muscle metabolism
0.00
Inflammation
0.00
Glucose metabolism
0.00
AA metabolism
0.00
Hormonal pathways
0.00
Cell death
0.00
Adipocyte fibrosis
0.00
Upstream (biochem)
0.00
Upstream (physiol)
0.00
Downstream (biochem)
0.00
Downstream (physiol)
0.00
PTMs
0.00
Экспрессия (8 полей)
Tissue expression
BDNF and phosphorylated CREB in hippocampus; miR-34a-5p in small intestine, peripheral blood, and hippocampus
0.90
In vitro
0.00
In vivo
Mouse model of total abdominal irradiation; metformin treatment; miR-34a-5p agomir injection
0.95
In silico
0.00
Genetic association
0.00
Ex vivo
0.00
Animal model
Mouse model
0.95
Diet/model
Total abdominal irradiation
0.95
Клиника (11 полей)
Drug
metformin
0.95
Indication
cognitive impairment caused by total abdominal irradiation
0.90
Patient subgroups
0.00
Safety concerns
0.00
Off-target
0.00
Trial stage
0.00
Pharma competitors
0.00
AE severity
0.00
MOA weight loss
0.00
Endpoints
0.00
Approved
0.00