Low-Dose Intranasal Metformin Exerts Neuroprotective Effects in a Rat Model of Sporadic Alzheimer's Disease

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dc.contributor.authorKurtukova, Vladislava
dc.contributor.authorAktas, Selen
dc.contributor.authorPupure, Jolanta
dc.contributor.authorNarbute, Karina
dc.contributor.authorMuceniece, Ruta
dc.contributor.authorPilipenko, Vladimirs
dc.date.accessioned2026-04-04T13:35:20Z
dc.date.available2026-04-04T13:35:20Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractCurrent therapies for sporadic Alzheimer's disease (sAD) provide only symptomatic relief, underscoring the need for treatments targeting its underlying pathophysiological mechanisms. Given the shared features between sAD and type 2 diabetes mellitus-particularly insulin resistance-repurposing antidiabetic agents like metformin has gained interest. Previous studies show that metformin rapidly reaches the brain following intranasal (i/n) administration and remains detectable for at least 2 h at a 3 mg/kg dose, supporting this delivery route for central nervous system targeting. I/n delivery of therapeutic agents bypasses the blood-brain barrier, enhances brain bioavailability, and minimizes peripheral side effects of such agents. In this preclinical study, we investigated whether low-dose i/n metformin (1 and 3 mg/kg) administered for 28 days could halt sAD-type changes. Our results demonstrate that i/n metformin improved cognitive function, including social behavior, in an intracerebroventricular streptozotocin (3 mg/kg)-induced rat model of sAD. Metformin administered i/n also reduced hippocampal microgliosis and apoptosis and enhanced phosphorylation of Akt and adenosine monophosphate-activated protein kinase. Moreover, it decreased hippocampal glycogen synthase kinase-3 beta levels, suggesting modulation of insulin signaling pathways. Notably, these neuroprotective effects were achieved at doses much lower than those used with systemic administration, underscoring the advantages of i/n delivery. Our findings suggest that low-dose i/n metformin is a promising, non-invasive, and disease-modifying therapeutic strategy for sAD, warranting further investigation.
dc.description.sponsorshipAAS MikroTik within the University of Latvia Foundation, patron of the University of Latvia [2261]
dc.description.sponsorshipThis study was supported by AAS MikroTik within the proposal call of the University of Latvia Foundation, patron of the University of Latvia (project No. 2261 Investigation of neurorestorative properties of metformin in an experimental model of Alzheimer's disease).
dc.identifier.doi10.1007/s12035-025-05079-x
dc.identifier.endpage13043
dc.identifier.issn0893-7648
dc.identifier.issn1559-1182
dc.identifier.issue10
dc.identifier.orcid0000-0002-7098-7483
dc.identifier.pmid40478515
dc.identifier.scopus2-s2.0-105007324468
dc.identifier.scopusqualityQ1
dc.identifier.startpage13029
dc.identifier.urihttps://doi.org/10.1007/s12035-025-05079-x
dc.identifier.urihttps://hdl.handle.net/11616/109789
dc.identifier.volume62
dc.identifier.wosWOS:001503264200001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMolecular Neurobiology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250329
dc.subjectAlzheimer's disease
dc.subjectNeuroprotection
dc.subjectMetformin
dc.subjectAMPK
dc.subjectMicroglia
dc.titleLow-Dose Intranasal Metformin Exerts Neuroprotective Effects in a Rat Model of Sporadic Alzheimer's Disease
dc.typeArticle

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