ArticleFEBS open bio2018
Metformin treatment ameliorates diabetes-associated decline in hippocampal neurogenesis and memory via phosphorylation of insulin receptor substrate 1.
Article in FEBS open bio, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Metformin and Sitagliptin Impact the Brain Kynurenine Pathway: Region-Specific Modulation of Neuroactive Metabolites in Non-Diabetic Male Rats.Molecules (Basel, Switzerland) · 2026Article
- Harmony in Motion: The Role of Exercise in Orchestrating Neuroprotection for Individuals with Alzheimer's Disease and Diabetes Examined from a Psychological Perspective.Current pharmaceutical biotechnology · 2026Review
- Low-Dose Intranasal Metformin Exerts Neuroprotective Effects in a Rat Model of Sporadic Alzheimer's Disease.Molecular neurobiology · 2025Article
- Metformin Improves Spatial Memory and Reduces Seizure Severity in a Rat Model of Epilepsy and Alzheimer's Disease comorbidity via PI3K/Akt Signaling Pathway.Molecular neurobiology · 2025Article
- Dehydrozingerone Improves Mood and Memory in Diabetic Mice via Modulating Core Neuroimmune Genes and Their Associated Proteins.ACS pharmacology & translational science · 2025Article
- Interactions between menopause and high-fat diet on cognition and pathology in a mouse model of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Inhibition of repulsive guidance molecule A ameliorates diabetes-induced cognitive decline and hippocampal neurogenesis impairment in mice.Communications biology · 2025Article
- Aerobic exercise and metformin attenuate the cognitive impairment in an experimental model of type 2 diabetes mellitus: focus on neuroinflammation and adult hippocampal neurogenesis.Metabolic brain disease · 2025Article
- Restorative effects of Momordica charantia extract on cerebellar GFAP and NGF expression in pregnant diabetic rats and their offspring.PloS one · 2025Article
- Metformin effectively alleviates the symptoms of Alzheimer in rats by lowering amyloid β deposition and enhancing the insulin signal.Metabolic brain disease · 2024Article
- Article
- Beneficial effects of metformin treatment on memory impairment.Molecular biology reports · 2024Review
- Therapeutic targeting of obesity-induced neuroinflammation and neurodegeneration.Frontiers in endocrinology · 2024Review
- Is metformin neuroprotective against diabetes mellitus-induced neurodegeneration? An updated graphical review of molecular basis.Pharmacological reports : PR · 2023Review
- The role of IGF-1 in exercise to improve obesity-related cognitive dysfunction.Frontiers in neuroscience · 2023Review
- Metformin inhibits cardiometabolic syndrome associated cognitive deficits in high fat diet rats.Journal of diabetes and metabolic disorders · 2022Article
- Effects of high-fat diet on nutrient metabolism and cognitive functions in young APPKINeuropsychopharmacology reports · 2022Article
- Research advances on how metformin improves memory impairment in "chemobrain".Neural regeneration research · 2022Article
- Metformin Alleviates Autistic-Like Behaviors Elicited by High-Fat Diet Consumption and Modulates the Crosstalk Between Serotonin and Gut Microbiota in Mice.Behavioural neurology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Age-related reduction in adult hippocampal neurogenesis is correlated with cognitive impairment. Diabetes is a chronic systemic disease that negatively affects adult neural stem cells and memory functions in the hippocampus. Despite growing concern regarding the potential role of diabetic drugs in neural abnormalities, their effects on progressive deterioration of neurogenesis and cognitive functions remain unknown. Here, we show that the combination of aging and diabetes in mice causes a marked decrease in hippocampal neurogenesis along with memory impairment and elevated neuroinflammation. Prolonged treatment with metformin, a biguanide antidiabetic medication, promotes cell proliferation and neuronal differentiation and inhibits aging- and diabetes-associated microglial activation, which is related to homeostatic neurogenesis, leading to enhanced hippocampal neurogenesis in middle-aged diabetic mice. Although chronic therapy with metformin fails to achieve recovery from hyperglycemia, a key feature of diabetes in middle-aged diabetic mice, it improves hippocampal-dependent spatial memory functions accompanied by increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), atypical protein kinase C ζ (aPKC ζ), and insulin receptor substrate 1 (IRS1) at selective serine residues in the hippocampus. Our findings suggest that signaling networks acting through long-term metformin-stimulated phosphorylation of AMPK, aPKC ζ/λ, and IRS1 serine sites contribute to neuroprotective effects on hippocampal neurogenesis and cognitive function independent of a hypoglycemic effect.
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